Cucurbitacin B and cancer intervention: Chemistry, biology and mechanisms (Review)
- Authors:
- Sukant Garg
- Sunil C. Kaul
- Renu Wadhwa
-
Affiliations: Drug Discovery and Assets Innovation Lab, DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan - Published online on: November 10, 2017 https://doi.org/10.3892/ijo.2017.4203
- Pages: 19-37
This article is mentioned in:
Abstract
Massagué J and Obenauf AC: Metastatic colonization by circulating tumour cells. Nature. 529:298–306. 2016. View Article : Google Scholar : PubMed/NCBI | |
World Health Organization: International Agency for Research on Cancer: World cancer factsheet. Cancer Research UK. http://gicr.iarc.fr/public/docs/20120906-WorldCancerFactSheet.pdf. Accessed June 20, 2017. | |
Cheung EC and Vousden KH: The role of p53 in glucose metabolism. Curr Opin Cell Biol. 22:186–191. 2010. View Article : Google Scholar : PubMed/NCBI | |
Engelmann D and Pützer BM: Emerging from the shade of p53 mutants: N-terminally truncated variants of the p53 family in EMT signaling and cancer progression. Sci Signal. 7:re92014. View Article : Google Scholar : PubMed/NCBI | |
Hengartner MO: The biochemistry of apoptosis. Nature. 407:770–776. 2000. View Article : Google Scholar : PubMed/NCBI | |
Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, Ashmun RA, Grosveld G and Sherr CJ: Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell. 91:649–659. 1997. View Article : Google Scholar : PubMed/NCBI | |
Korenjak M and Brehm A: E2F-Rb complexes regulating transcription of genes important for differentiation and development. Curr Opin Genet Dev. 15:520–527. 2005. View Article : Google Scholar : PubMed/NCBI | |
Sharpless NE, Alson S, Chan S, Silver DP, Castrillon DH and DePinho RA: p16INK4a and p53 deficiency cooperate in tumorigenesis. Cancer Res. 62:2761–2765. 2002.PubMed/NCBI | |
Stott FJ, Bates S, James MC, McConnell BB, Starborg M, Brookes S, Palmero I, Ryan K, Hara E, Vousden KH, et al: The alternative product from the human CDKN2A locus, p14ARF, participates in a regulatory feedback loop with p53 and MDM2. EMBO J. 17:5001–5014. 1998. View Article : Google Scholar : PubMed/NCBI | |
Dakeng S, Duangmano S, Jiratchariyakul W, U-Pratya Y, Bögler O and Patmasiriwat P: Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: Reduction of Wnt-associated proteins and reduced translocation of galectin-3-mediated β-catenin to the nucleus. J Cell Biochem. 113:49–60. 2012. View Article : Google Scholar | |
Nefedova Y and Gabrilovich DI: Targeting of Jak/STAT pathway in antigen presenting cells in cancer. Curr Cancer Drug Targets. 7:71–77. 2007. View Article : Google Scholar : PubMed/NCBI | |
Hung MH, Tai WT, Shiau CW and Chen KF: Downregulation of signal transducer and activator of transcription 3 by sorafenib: A novel mechanism for hepatocellular carcinoma therapy. World J Gastroenterol. 20:15269–15274. 2014. View Article : Google Scholar : PubMed/NCBI | |
Hossain DM, Pal SK, Moreira D, Duttagupta P, Zhang Q, Won H, Jones J, D'Apuzzo M, Forman S and Kortylewski M: TLR9-targeted STAT3 silencing abrogates immunosuppressive activity of myeloid-derived suppressor cells from prostate cancer patients. Clin Cancer Res. 21:3771–3782. 2015. View Article : Google Scholar : PubMed/NCBI | |
Liu H, Ren G, Wang T, Chen Y, Gong C, Bai Y, Wang B, Qi H, Shen J, Zhu L, et al: Aberrantly expressed Fra1 by IL6/STAT3 transactivation promotes colorectal cancer aggressiveness through epithelial mesenchymal transition. Carcinogenesis. 36:4594682015. View Article : Google Scholar | |
Peyser ND, Freilino M, Wang L, Zeng Y, Li H, Johnson DE and Grandis JR: Frequent promoter hypermethylation of PTPRT increases STAT3 activation and sensitivity to STAT3 inhibition in head and neck cancer. Oncogene. 35:1163–1169. 2016. View Article : Google Scholar | |
Wen W, Wu J, Liu L, Tian Y, Buettner R, Hsieh MY, Horne D, Dellinger TH, Han ES, Jove R, et al: Synergistic anti-tumor effect of combined inhibition of EGFR and JAK/STAT3 pathways in human ovarian cancer. Mol Cancer. 14:1002015. View Article : Google Scholar : PubMed/NCBI | |
Yao X, Liu H, Zhang X, Zhang L, Li X, Wang C and Sun S: Cell surface GRP78 accelerated breast cancer cell proliferation and migration by activating STAT3. PLoS One. 10:e01256342015. View Article : Google Scholar : PubMed/NCBI | |
Yoon J, Ko YS, Cho SJ, Park J, Choi YS, Choi Y, Pyo JS, Ye SK, Youn HD, Lee JS, et al: Signal transducers and activators of transcription 3-induced metastatic potential in gastric cancer cells is enhanced by glycogen synthase kinase-3β. APMIS. 123:373–382. 2015. View Article : Google Scholar | |
Royds JA, Dower SK, Qwarnstrom EE and Lewis CE: Response of tumour cells to hypoxia: Role of p53 and NF-κB. Mol Pathol. 51:55–61. 1998. View Article : Google Scholar : PubMed/NCBI | |
Bulavin DV and Fornace AJ Jr: p38 MAP kinase's emerging role as a tumor suppressor. Adv Cancer Res. 92:95–118. 2004. View Article : Google Scholar : PubMed/NCBI | |
Pal I and Mandal M: PI3K and Akt as molecular targets for cancer therapy: Current clinical outcomes. Acta Pharmacol Sin. 33:1441–1458. 2012. View Article : Google Scholar : PubMed/NCBI | |
Harley CB: Aging of cultured human skin fibroblasts. Methods Mol Biol. 5:25–32. 1990.PubMed/NCBI | |
Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 37:614–636. 1965. View Article : Google Scholar : PubMed/NCBI | |
Kimmelman AC and White E: Autophagy and tumor metabolism. Cell Metab. 25:1037–1043. 2017. View Article : Google Scholar : PubMed/NCBI | |
Kaefer CM and Milner JA: Herbs and Spices in Cancer Prevention and Treatment. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. CRC Press/Taylor & Francis; 2011, View Article : Google Scholar | |
Kaushik U, Aeri V and Mir SR: Cucurbitacins - An insight into medicinal leads from nature. Pharmacogn Rev. 9:12–18. 2015. View Article : Google Scholar : PubMed/NCBI | |
Alghasham AA: Cucurbitacins - a promising target for cancer therapy. Int J Health Sci (Qassim). 7:77–89. 2013. View Article : Google Scholar | |
Clericuzio M, Mella M, Vita-Finzi P, Zema M and Vidari G: Cucurbitane triterpenoids from Leucopaxillus gentianeus. J Nat Prod. 67:1823–1828. 2004. View Article : Google Scholar : PubMed/NCBI | |
Chen JC, Chiu MH, Nie RL, Cordell GA and Qiu SX: Cucurbitacins and cucurbitane glycosides: Structures and biological activities. Nat Prod Rep. 22:386–399. 2005. View Article : Google Scholar : PubMed/NCBI | |
Clericuzio M, Tabasso S, Bianco MA, Pratesi G, Beretta G, Tinelli S, Zunino F and Vidari G: Cucurbitane triterpenes from the fruiting bodies and cultivated mycelia of Leucopaxillus gentianeus. J Nat Prod. 69:1796–1799. 2006. View Article : Google Scholar : PubMed/NCBI | |
Wiart C: The definition and significance of Cucurbitacin B a STAT3 inhibitors. Cancer Lett. 328:1882013. View Article : Google Scholar | |
Dantas INF, Gadelha GCM, Chaves DC, Monte FJQ, Pessoa C, de Moraes MO and Costa-Lotufo LV: Studies on the cytotoxicity of cucurbitacins isolated from Cayaponia racemosa (Cucurbitaceae). Z Naturforsch C. 61:643–646. 2006.PubMed/NCBI | |
Hatam NAR, Whiting DA and Yousif NJ: Cucurbitacin glycosides from Citrullus colocynthis. Phytohemistry. 28:1268–1271. 1989. View Article : Google Scholar | |
Abou-Khalil R, Jraij A, Magdalou J, Ouaini N, Tome D and Greige-Gerges H: Interaction of cucurbitacins with human serum albumin: Thermodynamic characteristics and influence on the binding of site specific ligands. J Photochem Photobiol B. 95:189–195. 2009. View Article : Google Scholar : PubMed/NCBI | |
Li K, Yu Y, Sun S, Liu Y, Garg S, Kaul SC, Lei Z, Gao R, Wadhwa R and Zhang Z: Functional characterization of anticancer activity in the aqueous extract of Helicteres angustifolia L. roots. PLoS One. 11:e01520172016. View Article : Google Scholar | |
Oberlies NH, Burgess JP, Navarro HA, Pinos RE, Soejarto DD, Farnsworth NR, Kinghorn AD, Wani MC and Wall ME: Bioactive constituents of the roots of Licania intrapetiolaris. J Nat Prod. 64:497–501. 2001. View Article : Google Scholar : PubMed/NCBI | |
Beutler JA, McCall KL, Herbert K, Herald DL, Pettit GR, Johnson T, Shoemaker RH and Boyd MR: Novel cytotoxic diterpenes from Casearia arborea. J Nat Prod. 63:657–661. 2000. View Article : Google Scholar : PubMed/NCBI | |
Ayyad SEN, Abdel-Lateff A, Basaif SA and Shier T: Cucurbitacins-type triterpene with potent activity on mouse embryonic fibroblast from Cucumis prophetarum, cucurbitaceae. Pharmacognosy Res. 3:189–193. 2011. View Article : Google Scholar : PubMed/NCBI | |
Chen C, Qiang S, Lou L and Zhao W: Cucurbitane-type triterpenoids from the stems of Cucumis melo. J Nat Prod. 72:824–829. 2009. View Article : Google Scholar : PubMed/NCBI | |
Dat NT, Jin X, Hong YS and Lee JJ: An isoaurone and other constituents from Trichosanthes kirilowii seeds inhibit hypoxia-inducible factor-1 and nuclear factor-kappaB. J Nat Prod. 73:1167–1169. 2010. View Article : Google Scholar : PubMed/NCBI | |
Wu KJ, Grandori C, Amacker M, Simon-Vermot N, Polack A, Lingner J and Dalla-Favera R: Direct activation of TERT transcription by c-MYC. Nat Genet. 21:220–224. 1999. View Article : Google Scholar : PubMed/NCBI | |
Yesilada E, Tanaka S, Sezik E and Tabata M: Isolation of an anti-inflammatory principle from the fruit juice of Ecballium elaterium. J Nat Prod. 51:504–508. 1988. View Article : Google Scholar : PubMed/NCBI | |
Rawat I, Sharma D and Goel HC: Antioxidant and anti-inflammatory potential of some dietary cucurbits. Oxid Antioxid Med Sci. 3:65–72. 2014. View Article : Google Scholar | |
Schabort JC and Potgieter JJ: A thin-layer and an improved paper-chromatographic methods for the separation of Cucurbitacin B and 23,24-dihydrocucurbitacin B. J Chromatog. 31:235–237. 1967. View Article : Google Scholar | |
Tannin-Spitz T, Grossman S, Dovrat S, Gottlieb HE and Bergman M: Growth inhibitory activity of cucurbitacin glucosides isolated from Citrullus colocynthis on human breast cancer cells. Biochem Pharmacol. 73:56–67. 2007. View Article : Google Scholar | |
Wakimoto N, Yin D, O'Kelly J, Haritunians T, Karlan B, Said J, Xing H and Koeffler HP: Cucurbitacin B has a potent antiproliferative effect on breast cancer cells in vitro and in vivo. Cancer Sci. 99:1793–1797. 2008. View Article : Google Scholar : PubMed/NCBI | |
Duangmano S, Dakeng S, Jiratchariyakul W, Suksamrarn A, Smith DR and Patmasiriwat P: Antiproliferative effects of cucurbitacin B in breast cancer cells: Down-regulation of the c-Myc/hTERT/telomerase pathway and obstruction of the cell cycle. Int J Mol Sci. 11:5323–5338. 2010. View Article : Google Scholar : PubMed/NCBI | |
Wu PL, Lin FW, Wu TS, Kuoh CS, Lee KH and Lee SJ: Cytotoxic and anti-HIV principles from the rhizomes of Begonia nantoensis. Chem Pharm Bull (Tokyo). 52:345–349. 2004. View Article : Google Scholar | |
Duangmano S, Sae-Lim P, Suksamrarn A, Domann FE and Patmasiriwat P: Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation. BMC Complement Altern Med. 12:1852012. View Article : Google Scholar : PubMed/NCBI | |
Promkan M, Dakeng S, Chakrabarty S, Bögler O and Patmasiriwat P: The effectiveness of cucurbitacin B in BRCA1 defective breast cancer cells. PLoS One. 8:e557322013. View Article : Google Scholar : PubMed/NCBI | |
Boone JJ, Bhosle J, Tilby MJ, Hartley JA and Hochhauser D: Involvement of the HER2 pathway in repair of DNA damage produced by chemotherapeutic agents. Mol Cancer Ther. 8:3015–3023. 2009. View Article : Google Scholar : PubMed/NCBI | |
Friedrichs K, Ruiz P, Franke F, Gille I, Terpe HJ and Imhof BA: High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival. Cancer Res. 55:901–906. 1995.PubMed/NCBI | |
Jones JL, Royall JE, Critchley DR and Walker RA: Modulation of myoepithelial-associated alpha6beta4 integrin in a breast cancer cell line alters invasive potential. Exp Cell Res. 235:325–333. 1997. View Article : Google Scholar : PubMed/NCBI | |
Desgrosellier JS and Cheresh DA: Integrins in cancer: Biological implications and therapeutic opportunities. Nat Rev Cancer. 10:9–22. 2010. View Article : Google Scholar | |
Gupta P and Srivastava SK: Inhibition of Integrin-HER2 signaling by Cucurbitacin B leads to in vitro and in vivo breast tumor growth suppression. Oncotarget. 5:1812–1828. 2014. View Article : Google Scholar : PubMed/NCBI | |
Gupta P and Srivastava SK: HER2 mediated de novo production of TGFβ leads to SNAIL driven epithelial-to-mesenchymal transition and metastasis of breast cancer. Mol Oncol. 8:1532–1547. 2014. View Article : Google Scholar : PubMed/NCBI | |
de Herreros AG, Peiró S, Nassour M and Savagner P: Snail family regulation and epithelial mesenchymal transitions in breast cancer progression. J Mammary Gland Biol Neoplasia. 15:135–147. 2010. View Article : Google Scholar : PubMed/NCBI | |
Ren G, Sha T, Guo J, Li W, Lu J and Chen X: Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells. J Nat Med. 69:522–530. 2015. View Article : Google Scholar : PubMed/NCBI | |
Sinha S, Khan S, Shukla S, Lakra AD, Kumar S, Das G, Maurya R and Meeran SM: Cucurbitacin B inhibits breast cancer metastasis and angiogenesis through VEGF-mediated suppression of FAK/MMP-9 signaling axis. Int J Biochem Cell Biol. 77(Pt A): 41–56. 2016. View Article : Google Scholar : PubMed/NCBI | |
Lang KL, Silva IT, Zimmermann LA, Machado VR, Teixeira MR, Lapuh MI, Galetti MA, Palermo JA, Cabrera GM, Bernardes LS, et al: Synthesis and cytotoxic activity evaluation of dihydrocucurbitacin B and cucurbitacin B derivatives. Bioorg Med Chem. 20:3016–3030. 2012. View Article : Google Scholar : PubMed/NCBI | |
Kausar H, Munagala R, Bansal SS, Aqil F, Vadhanam MV and Gupta RC: Cucurbitacin B potently suppresses non-small-cell lung cancer growth: Identification of intracellular thiols as critical targets. Cancer Lett. 332:35–45. 2013. View Article : Google Scholar : PubMed/NCBI | |
Guo J, Wu G, Bao J, Hao W, Lu J and Chen X: Cucurbitacin B induced ATM-mediated DNA damage causes G2/M cell cycle arrest in a ROS-dependent manner. PLoS One. 9:e881402014. View Article : Google Scholar : PubMed/NCBI | |
Zhang M, Bian ZG, Zhang Y, Wang JH, Kan L, Wang X, Niu HY and He P: Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung cancer cells. Mol Med Rep. 10:2905–2911. 2014. View Article : Google Scholar : PubMed/NCBI | |
Shukla S, Khan S, Kumar S, Sinha S, Farhan M, Bora HK, Maurya R and Meeran SM: Cucurbitacin B alters the expression of tumor-related genes by epigenetic modifications in NSCLC and inhibits NNK-induced lung tumorigenesis. Cancer Prev Res (Phila). 8:552–562. 2015. View Article : Google Scholar | |
Silva IT, Geller FC, Persich L, Dudek SE, Lang KL, Caro MS, Durán FJ, Schenkel EP, Ludwig S and Simões CM: Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549. Invest New Drugs. 34:139–148. 2016. View Article : Google Scholar : PubMed/NCBI | |
Shukla S, Sinha S, Khan S, Kumar S, Singh K, Mitra K, Maurya R and Meeran SM: Cucurbitacin B inhibits the stemness and metastatic abilities of NSCLC via downregulation of canonical Wnt/β-catenin signaling axis. Sci Rep. 6:218602016. View Article : Google Scholar | |
Zhang Y, Ouyang D, Xu L, Ji Y, Zha Q, Cai J and He X: Cucurbitacin B induces rapid depletion of the G-actin pool through reactive oxygen species-dependent actin aggregation in melanoma cells. Acta Biochim Biophys Sin (Shanghai). 43:556–567. 2011. View Article : Google Scholar | |
Bamburg JR and Bernstein BW: Roles of ADF/cofilin in actin polymerization and beyond. F1000 Biol Rep. 2:622010.PubMed/NCBI | |
Wang W, Eddy R and Condeelis J: The cofilin pathway in breast cancer invasion and metastasis. Nat Rev Cancer. 7:429–440. 2007. View Article : Google Scholar : PubMed/NCBI | |
Van Troys M, Huyck L, Leyman S, Dhaese S, Vandekerkhove J and Ampe C: Ins and outs of ADF/cofilin activity and regulation. Eur J Cell Biol. 87:649–667. 2008. View Article : Google Scholar : PubMed/NCBI | |
Bamburg JR, Bernstein BW, Davis RC, Flynn KC, Goldsbury C, Jensen JR, Maloney MT, Marsden IT, Minamide LS, Pak CW, et al: ADF/Cofilin-actin rods in neurodegenerative diseases. Curr Alzheimer Res. 7:241–250. 2010. View Article : Google Scholar : PubMed/NCBI | |
Zhang YT, Ouyang DY, Xu LH, Zha QB and He XH: Formation of cofilin-actin rods following cucurbitacin-B-induced actin aggregation depends on Slingshot homolog 1-mediated cofilin hyperactivation. J Cell Biochem. 114:2415–2429. 2013. View Article : Google Scholar : PubMed/NCBI | |
Trichet L, Sykes C and Plastino J: Relaxing the actin cytoskeleton for adhesion and movement with Ena/VASP. J Cell Biol. 181:19–25. 2008. View Article : Google Scholar : PubMed/NCBI | |
Zhang YT, Xu LH, Lu Q, Liu KP, Liu PY, Ji F, Liu XM, Ouyang DY and He XH: VASP activation via the Gα13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation. PLoS One. 9:e935472014. View Article : Google Scholar | |
Yin D, Wakimoto N, Xing H, Lu D, Huynh T, Wang X, Black KL and Koeffler HP: Cucurbitacin B markedly inhibits growth and rapidly affects the cytoskeleton in glioblastoma multiforme. Int J Cancer. 123:1364–1375. 2008. View Article : Google Scholar : PubMed/NCBI | |
Touihri-Barakati I, Kallech-Ziri O, Ayadi W, Kovacic H, Hanchi B, Hosni K and Luis J: Cucurbitacin B purified from Ecballium elaterium (L.) A. Rich from Tunisia inhibits α5β1 integrin-mediated adhesion, migration, proliferation of human glioblastoma cell line and angiogenesis. Eur J Pharmacol. 797:153–161. 2017. View Article : Google Scholar : PubMed/NCBI | |
Zheng Q, Liu Y, Liu W, Ma F, Zhou Y, Chen M, Chang J, Wang Y, Yang G and He G: Cucurbitacin B inhibits growth and induces apoptosis through the JAK2/STAT3 and MAPK pathways in SH-SY5Y human neuroblastoma cells. Mol Med Rep. 10:89–94. 2014. View Article : Google Scholar : PubMed/NCBI | |
Shang Y, Guo XX, Li WW, Rao W, Chen ML, Mu LN and Li SJ: Cucurbitacin-B inhibits neuroblastoma cell proliferation through up-regulation of PTEN. Eur Rev Med Pharmacol Sci. 18:3297–3303. 2014.PubMed/NCBI | |
Chan KT, Meng FY, Li Q, Ho CY, Lam TS, To Y, Lee WH, Li M, Chu KH and Toh M: Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration. Cancer Lett. 294:118–124. 2010. View Article : Google Scholar : PubMed/NCBI | |
Niu Y, Sun W, Lu JJ, Ma DL, Leung CH, Pei L and Chen X: PTEN activation by DNA damage induces protective autophagy in response to cucurbitacin B in hepatocellular carcinoma cells. Oxid Med Cell Longev. 2016:43132042016. View Article : Google Scholar | |
Haritunians T, Gueller S, Zhang L, Badr R, Yin D, Xing H, Fung MC and Koeffler HP: Cucurbitacin B induces differentiation, cell cycle arrest, and actin cytoskeletal alterations in myeloid leukemia cells. Leuk Res. 32:1366–1373. 2008. View Article : Google Scholar : PubMed/NCBI | |
Chan KT, Li K, Liu SL, Chu KH, Toh M and Xie WD: Cucurbitacin B inhibits STAT3 and the Raf/MEK/ERK pathway in leukemia cell line K562. Cancer Lett. 289:46–52. 2010. View Article : Google Scholar | |
Zhu JS, Ouyang DY, Shi ZJ, Xu LH, Zhang YT and He XH: Cucurbitacin B induces cell cycle arrest, apoptosis and autophagy associated with G actin reduction and persistent activation of cofilin in Jurkat cells. Pharmacology. 89:348–6. 2012. View Article : Google Scholar : PubMed/NCBI | |
Gao Y, Islam MS, Tian J, Lui VWY and Xiao D: Inactivation of ATP citrate lyase by Cucurbitacin B: A bioactive compound from cucumber, inhibits prostate cancer growth. Cancer Lett. 349:15–25. 2014. View Article : Google Scholar : PubMed/NCBI | |
Zaidi N, Swinnen JV and Smans K: ATP-citrate lyase: A key player in cancer metabolism. Cancer Res. 72:3709–3714. 2012. View Article : Google Scholar : PubMed/NCBI | |
Zaytseva YY, Rychahou PG, Gulhati P, Elliott VA, Mustain WC, O'Connor K, Morris AJ, Sunkara M, Weiss HL, Lee EY, et al: Inhibition of fatty acid synthase attenuates CD44-associated signaling and reduces metastasis in colorectal cancer. Cancer Res. 72:1504–1517. 2012. View Article : Google Scholar : PubMed/NCBI | |
Liu T, Zhang M, Zhang H, Sun C and Deng Y: Inhibitory effects of cucurbitacin B on laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 265:1225–1232. 2008. View Article : Google Scholar : PubMed/NCBI | |
Xie YL, Tao WH, Yang TX and Qiao JG: Anticancer effect of cucurbitacin B on MKN-45 cells via inhibition of the JAK2/STAT3 signaling pathway. Exp Ther Med. 12:2709–2715. 2016. View Article : Google Scholar : PubMed/NCBI | |
Liu X, Duan C, Ji J, Zhang T, Yuan X, Zhang Y, Ma W, Yang J, Yang L, Jiang Z, et al: Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 signaling axis in human cisplatin resistant gastric cancer cells. Oncol Rep. 38:271–278. 2017. View Article : Google Scholar : PubMed/NCBI | |
Zhang ZR, Gao MX and Yang K: Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways. Exp Ther Med. 14:805–812. 2017. View Article : Google Scholar : PubMed/NCBI | |
Qu Y, Cong P, Lin C, Deng Y, Li-Ling J and Zhang M: Inhibition of paclitaxel resistance and apoptosis induction by cucurbitacin B in ovarian carcinoma cells. Oncol Lett. 14:145–152. 2017.PubMed/NCBI | |
Ma J, Zi Jiang Y, Shi H, Mi C, Li J, Xing Nan J, Wu X, Joon Lee J and Jin X: Cucurbitacin B inhibits the translational expression of hypoxia-inducible factor-1α. Eur J Pharmacol. 723:46–54. 2014. View Article : Google Scholar | |
Wang X, Tanaka M, Peixoto HS and Wink M: Cucurbitacins: Elucidation of their interactions with the cytoskeleton. PeerJ. 5:e33572017. View Article : Google Scholar : PubMed/NCBI | |
Zhang T, Li Y, Park KA, Byun HS, Won M, Jeon J, Lee Y, Seok JH, Choi SW, Lee SH, et al: Cucurbitacin induces autophagy through mitochondrial ROS production which counteracts to limit caspase-dependent apoptosis. Autophagy. 8:559–576. 2012. View Article : Google Scholar : PubMed/NCBI | |
Marostica LL, Silva IT, Kratz JM, Persich L, Geller FC, Lang KL, Caro MSB, Durán FJ, Schenkel EP and Simões CM: Synergetic antiproliferative effects of a new cucurbitacin B derivative and chemotherapy drugs on lung cancer cell line A549. Chem Res Toxicol. 28:1949–1960. 2015. View Article : Google Scholar : PubMed/NCBI | |
Silva IT, Carvalho A, Lang KL, Dudek SE, Masemann D, Durán FJ, Caro MSB, Rapp UR, Wixler V, Schenkel EP, et al: In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B. PLoS One. 10:e01177942015. View Article : Google Scholar : PubMed/NCBI | |
Chen W, Leiter A, Yin D, Meiring M, Louw VJ and Koeffler HP: Cucurbitacin B inhibits growth, arrests the cell cycle, and potentiates antiproliferative efficacy of cisplatin in cutaneous squamous cell carcinoma cell lines. Int J Oncol. 37:737–743. 2010.PubMed/NCBI | |
Liu T, Peng H, Zhang M, Deng Y and Wu Z: Cucurbitacin B, a small molecule inhibitor of the Stat3 signaling pathway, enhances the chemosensitivity of laryngeal squamous cell carcinoma cells to cisplatin. Eur J Pharmacol. 641:15–22. 2010. View Article : Google Scholar : PubMed/NCBI | |
El-Senduny FF, Badria FA, El-Waseef AM, Chauhan SC and Halaweish F: Approach for chemosensitization of cisplatin-resistant ovarian cancer by cucurbitacin B. Tumour Biol. 37:685–698. 2016. View Article : Google Scholar | |
Marostica LL, de Barros ALB, Oliveira J, Salgado BS, Cassali GD, Leite EA, Cardoso VN, Lang KL, Caro MSB, Durán FJ, et al: Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model. Toxicol Appl Pharmacol. 329:272–281. 2017. View Article : Google Scholar : PubMed/NCBI | |
Aribi A, Gery S, Lee DH, Thoennissen NH, Thoennissen GB, Alvarez R, Ho Q, Lee K, Doan NB, Chan KT, et al: The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer. Int J Cancer. 132:2730–2737. 2013. View Article : Google Scholar | |
Liu T, Zhang M, Zhang H, Sun C, Yang X, Deng Y and Ji W: Combined antitumor activity of cucurbitacin B and docetaxel in laryngeal cancer. Eur J Pharmacol. 587:78–84. 2008. View Article : Google Scholar : PubMed/NCBI | |
Thoennissen NH, Iwanski GB, Doan NB, Okamoto R, Lin P, Abbassi S, Song JH, Yin D, Toh M, Xie WD, et al: Cucurbitacin B induces apoptosis by inhibition of the JAK/STAT pathway and potentiates antiproliferative effects of gemcitabine on pancreatic cancer cells. Cancer Res. 69:5876–5884. 2009. View Article : Google Scholar : PubMed/NCBI | |
Iwanski GB, Lee DH, En-Gal S, Doan NB, Castor B, Vogt M, Toh M, Bokemeyer C, Said JW, Thoennissen NH, et al: Cucurbitacin B, a novel in vivo potentiator of gemcitabine with low toxicity in the treatment of pancreatic cancer. Br J Pharmacol. 160:998–1007. 2010. View Article : Google Scholar : PubMed/NCBI | |
Yar Saglam AS, Alp E, Elmazoglu Z and Menevse S: Treatment with cucurbitacin B alone and in combination with gefitinib induces cell cycle inhibition and apoptosis via EGFR and JAK/STAT pathway in human colorectal cancer cell lines. Hum Exp Toxicol. 35:526–543. 2016. View Article : Google Scholar | |
Lee DH, Thoennissen NH, Goff C, Iwanski GB, Forscher C, Doan NB, Said JW and Koeffler HP: Synergistic effect of low-dose cucurbitacin B and low-dose methotrexate for treatment of human osteosarcoma. Cancer Lett. 306:161–170. 2011. View Article : Google Scholar : PubMed/NCBI | |
Tacar O, Sriamornsak P and Dass CR: Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol. 65:157–170. 2013. View Article : Google Scholar : PubMed/NCBI | |
Zhang Z, Zhang Y, Lv J and Wang J: The survivin suppressant YM155 reverses doxorubicin resistance in osteosarcoma. Int J Clin Exp Med. 8:18032–18040. 2015. | |
Kim SH, Kang JG, Kim CS, Ihm SH, Choi MG, Yoo HJ and Lee SJ: Doxorubicin has a synergistic cytotoxicity with cucurbitacin B in anaplastic thyroid carcinoma cells. Tumour Biol. 39:10104283176922522017.PubMed/NCBI | |
Yang T, Liu J, Yang M, Huang N, Zhong Y, Zeng T, Wei R, Wu Z, Xiao C, Cao X, et al: Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways. Oncotarget. 8:5800–5813. 2017. | |
Di Gennaro E, Bruzzese F, Pepe S, Leone A, Delrio P, Subbarayan PR, Avallone A and Budillon A: Modulation of thymidilate synthase and p53 expression by HDAC inhibitor vorinostat resulted in synergistic antitumor effect in combination with 5FU or raltitrexed. Cancer Biol Ther. 8:782–791. 2009. View Article : Google Scholar : PubMed/NCBI | |
Ouyang D, Zhang Y, Xu L, Li J, Zha Q and He X: Histone deacetylase inhibitor valproic acid sensitizes B16F10 melanoma cells to cucurbitacin B treatment. Acta Biochim Biophys Sin (Shanghai). 43:487–495. 2011. View Article : Google Scholar | |
Lee HI, McGregor RA, Choi MS, Seo KI, Jung UJ, Yeo J, Kim MJ and Lee MK: Low doses of curcumin protect alcohol-induced liver damage by modulation of the alcohol metabolic pathway, CYP2E1 and AMPK. Life Sci. 93:693–699. 2013. View Article : Google Scholar : PubMed/NCBI | |
García-Niño WR and Pedraza-Chaverrí J: Protective effect of curcumin against heavy metals-induced liver damage. Food Chem Toxicol. 69:182–201. 2014. View Article : Google Scholar : PubMed/NCBI | |
Cerný D, Lekić N, Váňová K, Muchová L, Hořínek A, Kmoníčková E, Zídek Z, Kameníková L and Farghali H: Hepatoprotective effect of curcumin in lipopolysaccharide/-galactosamine model of liver injury in rats: Relationship to HO-1/CO antioxidant system. Fitoterapia. 82:786–791. 2011. View Article : Google Scholar : PubMed/NCBI | |
Aggarwal BB, Kumar A and Bharti AC: Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res. 23(1A): 363–398. 2003.PubMed/NCBI | |
Sun Y, Zhang J, Zhou J, Huang Z, Hu H, Qiao M, Zhao X and Chen D: Synergistic effect of cucurbitacin B in combination with curcumin via enhancing apoptosis induction and reversing multidrug resistance in human hepatoma cells. Eur J Pharmacol. 768:28–40. 2015. View Article : Google Scholar : PubMed/NCBI | |
Tannin-Spitz T, Bergman M and Grossman S: Cucurbitacin glucosides: Antioxidant and free-radical scavenging activities. Biochem Biophys Res Commun. 364:181–186. 2007. View Article : Google Scholar : PubMed/NCBI | |
Duangmano S, Sae-Lim P, Suksamrarn A, Patmasiriwat P and Domann FE: Cucurbitacin B causes increased radiation sensitivity of human breast cancer cells via G2/M cell cycle arrest. J Oncol. 2012:6016822012. View Article : Google Scholar : PubMed/NCBI | |
Smit HF, van den Berg AJJ, Kroes BH, Beukelman CJ, Quarles van Ufford HC, van Dijk H and Labadie RP and Labadie RP: Inhibition of T-lymphocyte proliferation by cucurbitacins from Picrorhiza scrophulariaeflora. J Nat Prod. 63:1300–1302. 2000. View Article : Google Scholar : PubMed/NCBI | |
Chen JC, Chiu MH, Nie RL, Cordell GA and Qiu SX: Cucurbitacins and cucurbitane glycosides: Structures and biological activities. Nat Prod Rep. 22:386–399. 2005. View Article : Google Scholar : PubMed/NCBI | |
Jayaprakasam B, Seeram NP and Nair MG: Anticancer and antiinflammatory activities of cucurbitacins from Cucurbita andreana. Cancer Lett. 189:11–16. 2003. View Article : Google Scholar | |
Miro M: Cucurbitacins and their pharmacological effects. Phytother Res. 9:159–168. 1995. View Article : Google Scholar | |
Xiao Y, Yang Z, Wu QQ, Jiang XH, Yuan Y, Chang W, Bian ZY, Zhu JX and Tang QZ: Cucurbitacin B: Cucurbitacin B protects against pressure overload induced cardiac hypertrophy. J Cell Biochem. 118:3899–3910. 2017. View Article : Google Scholar : PubMed/NCBI | |
Hua S, Liu X, Lv S and Wang Z: Protective effects of Cucurbitacin B on acute lung injury induced by sepsis in rats. Med Sci Monit. 23:1355–1362. 2017. View Article : Google Scholar : PubMed/NCBI | |
El Naggar MB, Chalupová M, Pražanová G, Parák T, Švajdlenka E, Žemlička M and Suchý P: Hepatoprotective and proapoptotic effect of Ecballium elaterium on CCl4-induced hepatotoxicity in rats. Asian Pac J Trop Med. 8:526–531. 2015. View Article : Google Scholar : PubMed/NCBI | |
Li ZJ, Shin JM, Choi DK, Lim SK, Yoon TJ, Lee YH, Sohn KC, Im M, Lee Y, Seo YJ, et al: Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation. Biochem Biophys Res Commun. 459:673–678. 2015. View Article : Google Scholar : PubMed/NCBI | |
Park SY, Kim YH and Park G: Cucurbitacins attenuate microglial activation and protect from neuroinflammatory injury through Nrf2/ARE activation and STAT/NF-κB inhibition. Neurosci Lett. 609:129–136. 2015. View Article : Google Scholar : PubMed/NCBI | |
Peters RR, Farias MR and Ribeiro-do-Valle RM: Anti-inflammatory and analgesic effects of cucurbitacins from Wilbrandia ebracteata. Planta Med. 63:525–528. 1997. View Article : Google Scholar | |
Seo CR, Yang DK, Song NJ, Yun UJ, Gwon AR, Jo DG, Cho JY, Yoon K, Ahn JY, Nho CW, et al: Cucurbitacin B and cucurbitacin I suppress adipocyte differentiation through inhibition of STAT3 signaling. Food Chem Toxicol. 64:217–224. 2014. View Article : Google Scholar | |
Hassan STS, Berchova-Bimova K, Petras J and Hassan KTS: Cucurbitacin B interacts synergistically with antibiotics against Staphylococcus aureus clinical isolates and exhibits antiviral activity against HSV-1. S Afr J Bot. 108:90–94. 2017. View Article : Google Scholar | |
Duportets L, Maria A, Vitecek S, Gadenne C and Debernard S: Steroid hormone signaling is involved in the age-dependent behavioral response to sex pheromone in the adult male moth Agrotis ipsilon. Gen Comp Endocrinol. 186:58–66. 2013. View Article : Google Scholar : PubMed/NCBI | |
Mezher M: The essential list of regulatory authorities in Asia. Regulatory Affairs Professional Society. published April 4, 2015. http://www.raps.org/Regulatory-Focus/News/Databases/2015/04/06/21908/The-Essential-List-of-Regulatory-Authorities-in-Asia/. Accessed Sep 29, 2017. | |
David A and Vallance DK: Bitter principles of Cucurbitaceae. J Pharm Pharmacol. 7:295–296. 1955. View Article : Google Scholar | |
Baxter H, Harborne JB and Moss GP: Phytochemical Dictionary: A Handbook of Bioactive Compounds from Plants. 2nd edition. Taylor & Francis Ltd; London, UK: pp. 7861999 | |
World Health Organization: WHO Monograph on Selected Medicinal Plants. 4:2662009. | |
Ferguson JE, Fischer DC and Metcalf RL: A report of Cucurbitacin poisonings in humans. Rep Cucurbit Genet Coop. 6:73–74. 1983. | |
Therapeutic Goods Association: Health Safety Regulation - Substances that may be used in listed medicines in Australia. Government of Australia. 862011. | |
Le Men J, Buffard G, Provost J, Tiberghien R, Forgacs P, Lagrange E, Albert O and Aurousseau M: Relations entre la structure de quelques cucurbitacines, leur toxicité et leur activité laxative. Chim Therapeutique. 4:459–465. 1969.In French. | |
Enslin PR: Bitter principles of the Cucurbitaceae I - observations on the chemistry of cucurbitacin A. J Sci Food Agric. 5:410–416. 1954. View Article : Google Scholar | |
Gry J, Soborg I and Anderson HC: Identity, physical and chemical properties, analytical methods. Cucurbitacins in plant food. Ekspressen Tyrk & Kopicenter, Copenhagen, Denmark. 182006. | |
Sezik E: Research on the Turkish medicinal plant Ecballium elaterium. Chem Nat Compd. 33:541–542. 1997. View Article : Google Scholar | |
Steyn DG: The toxicity of bitter-tasting cucurbitaceous vegetables (vegetable marrow, watermelons, etc) for man. S Afr Med J. 24:713–715. 1950.PubMed/NCBI | |
Stoewsand GS, Jaworski A, Shannon S and Robinson RW: Toxicologic response in mice fed Cucurbita fruit. J Food Prot. 48:50–51. 1985. View Article : Google Scholar | |
Barri MES, Onsa TO, Elawad AA, Elsayed NY, Wasfi IA, Abdul-Bari EM and Adam SEI: Toxicity of five Sudanese plants to young ruminants. J Comp Pathol. 93:559–575. 1983. View Article : Google Scholar : PubMed/NCBI | |
Bakhiet AO and Adam SE: An estimation of Citrullus colocynthis toxicity for chicks. Vet Hum Toxicol. 37:356–358. 1995.PubMed/NCBI | |
Rymal KS, Chambliss OL, Bond MD and Smith DA: Squash containing toxic Cucurbitacin compounds occurring in California and Alabama. J Food Prot. 47:270–271. 1984. View Article : Google Scholar | |
Pilegaard K and Søborg I: Squash med bitter smag. Nyt Levnedsmiddelstyrelsen Nr. 23:1995.In Danish. | |
Raikhlin-Eisenkraft B and Bentur Y: Ecbalium elaterium (squirting cucumber) - remedy or poison? J Toxicol Clin Toxicol. 38:305–308. 2000. View Article : Google Scholar | |
Jung ME and Lui RM: Studies toward the total syntheses of cucurbitacins B and D. J Org Chem. 75:7146–7158. 2010. View Article : Google Scholar : PubMed/NCBI | |
Razavilar N and Choi P: Molecular dynamics study of the diffusivity of a hydrophobic drug Cucurbitacin B in pseudo-poly(ethylene oxide-b-caprolactone) micelle environments. Langmuir. 30:7798–7803. 2014. View Article : Google Scholar : PubMed/NCBI | |
Toker G, Memişoğlu M, Toker MC and Yeşilada E: Callus formation and cucurbitacin B accumulation in Ecballium elaterium callus cultures. Fitoterapia. 74:618–623. 2003. View Article : Google Scholar : PubMed/NCBI | |
Mei J, Li S, Jin H, Tang L, Yi Y, Wang H and Ying G: A biotransformation process for the production of cucurbitacin B from its glycoside using a selected Streptomyces sp. Bioprocess Biosyst Eng. 39:1435–1440. 2016. View Article : Google Scholar : PubMed/NCBI | |
Lv Q, Shen C, Li X, Shen B, Yu C, Xu P, Xu H, Han J and Yuan H: Mucoadhesive buccal films containing phospholipid-bile salts-mixed micelles as an effective carrier for cucurbitacin B delivery. Drug Deliv. 22:351–358. 2015. View Article : Google Scholar | |
Molavi O, Ma Z, Mahmud A, Alshamsan A, Samuel J, Lai R, Kwon GS and Lavasanifar A: Polymeric micelles for the solubilization and delivery of STAT3 inhibitor cucurbitacins in solid tumors. Int J Pharm. 347:118–127. 2008. View Article : Google Scholar | |
Patel SK, Lavasanifar A and Choi P: Roles of nonpolar and polar intermolecular interactions in the improvement of the drug loading capacity of PEO-b-PCL with increasing PCL content for two hydrophobic Cucurbitacin drugs. Biomacromolecules. 10:2584–2591. 2009. View Article : Google Scholar : PubMed/NCBI | |
Cheng L, Xu PH, Shen BD, Shen G, Li JJ, Qiu L, Liu CY, Yuan HL and Han J: Improve bile duct-targeted drug delivery and therapeutic efficacy for cholangiocarcinoma by cucurbitacin B loaded phospholipid complex modified with berberine hydrochloride. Int J Pharm. 489:148–157. 2015. View Article : Google Scholar : PubMed/NCBI | |
Wang W, Zhao X, Hu H, Chen D, Gu J, Deng Y and Sun J: Galactosylated solid lipid nanoparticles with cucurbitacin B improves the liver targetability. Drug Deliv. 17:114–122. 2010. View Article : Google Scholar : PubMed/NCBI | |
You L, Wang Z, Li H, Shou J, Jing Z, Xie J, Sui X, Pan H and Han W: The role of STAT3 in autophagy. Autophagy. 11:729–739. 2015. View Article : Google Scholar : PubMed/NCBI |