The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment (Review)

Jia,Lili; Ma,Shumei; Hou,Xue; Wang,Xin; Qased,Abu Baker Layth; Sun,Xuefei; Liang,Nan; Li,Huicheng; Yi,Heqing; Kong,Dejuan; Liu,Xiaodong; Fan,Feiyue

doi:10.3892/ol.2013.1245

The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment (Review)

Authors:
- Lili Jia
- Shumei Ma
- Xue Hou
- Xin Wang
- Abu Baker Layth Qased
- Xuefei Sun
- Nan Liang
- Huicheng Li
- Heqing Yi
- Dejuan Kong
- Xiaodong Liu
- Feiyue Fan
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Affiliations: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun 130021, P.R. China, Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun 130021, P.R. China, Department of Radiation Oncology and Radiology, China-Japan Union Hospital, Changchun 130021, P.R. China, Department of Surgery, Norman Bethune Second Hospital Affiliated to Jilin University, Changchun 130021, P.R. China, Department of Radiation Oncology and Radiology, China-Japan Union Hospital, Changchun 130021, P.R. China, Department of Radiotherapy, Norman Bethune Fourth Hospital Affiliated to Jilin University, Changchun, 130011, P.R. China, Department of Radiation Hazard Evaluation, Institute of Radiation Medicine of Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, P.R. China
Published online on: March 12, 2013 https://doi.org/10.3892/ol.2013.1245
Pages: 1439-1447

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Abstract

Traditional Chinese medicine (TCM) has been demonstrated to have potent cytotoxic activity against certain malignant tumors. Ionizing radiation (IR) is one of the most effective methods used in the clinical treatment of cancer. The drawback of a single formula is that it limits the treatment efficacy for cancer, while comprehensive strategies require additional theoretical support. However, a combination of different antitumor treatment modalities is advantageous in restricting the non-specific toxicity often observed with an extremely high dose of a single regimen. The induction of apoptotic cell death is a significant process in tumor cells following radiotherapy or chemotherapy, and resistance to these treatments has been linked to a low propensity for apoptosis. Autophagy is a response of cancer cells to IR or chemotherapy, and involves the prominent formation of autophagic vacuoles in the cytoplasm. In this review, the synergistic effects of TCM and radiotherapy are summarized and the underlying mechanisms are illustrated, providing new therapeutic strategies for cancer.

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1	Gao JL, Shi JM, He K, et al: Yanhusuo extract inhibits metastasis of breast cancer cells by modulating mitogen-activated protein kinase signaling pathways. Oncol Rep. 20:819–824. 2008.PubMed/NCBI
2	Pang X, Yi Z, Zhang J, et al: Celastrol suppresses angiogenesis-mediated tumor growth through inhibition of AKT/mammalian target of rapamycin pathway. Cancer Res. 70:1951–1959. 2010. View Article : Google Scholar : PubMed/NCBI
3	Wang Y, Dong H, Zhu M, et al: Icariin exterts negative effects on human gastric cancer cell invasion and migration by vasodilator-stimulated phosphoprotein via Rac1 pathway. Eur J Pharmacol. 635:40–48. 2010. View Article : Google Scholar
4	Pan TL, Hung YC, Wang PW, et al: Functional proteomic and structural insights into molecular targets related to the growth inhibitory effect of tanshinone IIA on HeLa cells. Proteomics. 10:914–929. 2010.PubMed/NCBI
5	Yuxian X, Feng T, Ren L and Zhengcai L: Tanshinone II-A inhibits invasion and metastasis of human hepatocellular carcinoma cells in vitro and in vivo. Tumori. 95:789–795. 2009.PubMed/NCBI
6	Duan H, Luan J, Liu Q, Yagasaki K and Zhang G: Suppression of human lung cancer cell growth and migration by berbamine. Cytotechnology. 62:341–348. 2010. View Article : Google Scholar : PubMed/NCBI
7	Chen D, Yao WJ, Zhang XL, et al: Effects of Gekko sulfated polysaccharide-protein complex on human hepatoma SMMC-7721 cells: inhibition of proliferation and migration. J Ethnopharmacol. 127:702–708. 2010. View Article : Google Scholar : PubMed/NCBI
8	Liu F, Wang JG, Wang SY, Li Y, Wu YP and Xi SM: Antitumor effect and mechanism of Gecko on human esophageal carcinoma cell lines in vitro and xenografted sarcoma 180 in Kunming mice. World J Gastroenterol. 14:3990–3996. 2008. View Article : Google Scholar : PubMed/NCBI
9	Hsu SC, Ou CC, Li JW, et al: Ganoderma tsugae extracts inhibit colorectal cancer cell growth via G(2)/M cell cycle arrest. J Ethnopharmacol. 120:394–401. 2008. View Article : Google Scholar
10	Zhang YK, Zhang XH, Li JM, Sun de S, Yang Q and Diao DM: A proteomic study on a human osteosarcoma cell line Saos-2 treated with diallyl trisulfide. Anticancer Drugs. 20:702–712. 2009. View Article : Google Scholar : PubMed/NCBI
11	Hsu HY, Hau DM and Lin CC: Effects of kuei-pi-tang on cellular immunocompetence of gamma-irradiated mice. Am J Chin Med. 21:151–158. 1993. View Article : Google Scholar : PubMed/NCBI
12	Yang MW, He MD and Li MZ: Effects of zaizhang-I, a traditional Chinese herbal medicine, on hematopoietic recovery from radiation injury in mice. J Tongji Med Univ. 14:224–226. 1994. View Article : Google Scholar : PubMed/NCBI
13	Ohnishi Y, Yasumizu R, Fan HX, et al: Effects of juzen-taiho-toh (TJ-48), a traditional Oriental medicine, on hematopoietic recovery from radiation injury in mice. Exp Hematol. 18:18–22. 1990.PubMed/NCBI
14	Fujii Y, Imamura M, Han M, et al: Recipient-mediated effect of a traditional Chinese herbal medicine, ren-shen-yang-rong-tang (Japanese name: ninjin-youei-to), on hematopoietic recovery following lethal irradiation and syngeneic bone marrow transplantation. Int J Immunopharmacol. 16:615–622. 1994. View Article : Google Scholar
15	Chen WC, Hau DM, Chen KT, Wang MI and Lin IH: Protective effects of Gynostemma pentaphyllum in gamma-irradiated mice. Am J Chin Med. 24:83–92. 1996.
16	Hsu HY and Lin CC: A preliminary study on the radioprotection of mouse hematopoiesis by dang-gui-shao-yao-san. J Ethnopharmacol. 55:43–48. 1996. View Article : Google Scholar : PubMed/NCBI
17	Chen WC, Hau DM and Lee SS: Effects of Ganoderma lucidum and krestin on cellular immunocompetence in gamma-ray-irradiated mice. Am J Chin Med. 23:71–80. 1995.
18	Lee SE, Oh H, Yang JA, et al: Radioprotective effects of two traditional Chinese medicine prescriptions: si-wu-tang and si-jun-zi-tang. Am J Chin Med. 27:387–396. 1999. View Article : Google Scholar : PubMed/NCBI
19	Lawenda BD: Response to “Radiation therapeutic gain and Asian botanicals,” by Stephen Sagar. Integr Cancer Ther. 9:14–15. 2010.
20	Reeve VE, Allanson M, Arun SJ, Domanski D and Painter N: Mice drinking goji berry juice (Lycium barbarum) are protected from UV radiation-induced skin damage via antioxidant pathways. Photochem Photobiol Sci. 9:601–607. 2010.PubMed/NCBI
21	Liu FY, Wang JN, Yu SD, Wang B and Zhang JD: Effect of panaxatriol on hematogenesis and granulocyte-macrophage colony stimulating factor in radiation injured mice. Saudi Med J. 28:1791–1795. 2007.PubMed/NCBI
22	Kim SH, Lee SE, Oh H, et al: The radioprotective effects of bu-zhong-yi-qi-tang: a prescription of traditional Chinese medicine. Am J Chin Med. 30:127–137. 2002. View Article : Google Scholar : PubMed/NCBI
23	Li CR, Zhou Z, Zhu D, Sun YN, Dai JM and Wang SQ: Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. Int J Biochem Cell Biol. 39:426–438. 2007. View Article : Google Scholar : PubMed/NCBI
24	Kim S and Chung JH: Berberine prevents UV-induced MMP-1 and reduction of type I procollagen expression in human dermal fibroblasts. Phytomedicine. 15:749–753. 2008. View Article : Google Scholar : PubMed/NCBI
25	Chiu TM, Huang CC, Lin TJ, Fang JY, Wu NL and Hung CF: In vitro and in vivo anti-photoaging effects of an isoflavone extract from soybean cake. J Ethnopharmacol. 126:108–113. 2009. View Article : Google Scholar
26	Dai AW, Li ZY, Wang LH, Li SY and Yang H: Effect of Yangyin Humo Decoction on oral mucomembranous reaction to radiotherapy. Chin J Integr Med. 15:303–306. 2009. View Article : Google Scholar : PubMed/NCBI
27	Wang ZW, Zhou JM, Huang ZS, et al: Aloe polysaccharides mediated radioprotective effect through the inhibition of apoptosis. J Radiat Res. 45:447–454. 2004. View Article : Google Scholar : PubMed/NCBI
28	Lu Y, Wu LQ, Dong Q and Li CS: Experimental study on the effect of Kang-Lai-Te induced apoptosis of human hepatoma carcinoma cell HepG2. Hepatobiliary Pancreat Dis Int. 8:267–272. 2009.PubMed/NCBI
29	Wang GY, Lv QH, Dong Q, Xu RZ and Dong QH: Berbamine induces Fas-mediated apoptosis in human hepatocellular carcinoma HepG2 cells and inhibits its tumor growth in nude mice. J Asian Nat Prod Res. 11:219–228. 2009. View Article : Google Scholar : PubMed/NCBI
30	Zhang Z, Wang S, Qiu H, Duan C, Ding K and Wang Z: Waltonitone induces human hepatocellular carcinoma cells apoptosis in vitro and in vivo. Cancer Lett. 286:223–231. 2009. View Article : Google Scholar : PubMed/NCBI
31	Sung B, Park B, Yadav VR and Aggarwal BB: Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and up-regulation of death receptors. J Biol Chem. 285:11498–11507. 2010. View Article : Google Scholar : PubMed/NCBI
32	Li W, Xie L, Chen Z, et al: Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis. Cancer Sci. 101:1226–1233. 2010. View Article : Google Scholar
33	Fang SC, Hsu CL, Lin HT and Yen GC: Anticancer effects of flavonoid derivatives isolated from Millettia reticulata Benth in SK-Hep-1 human hepatocellular carcinoma cells. J Agric Food Chem. 58:814–820. 2010. View Article : Google Scholar : PubMed/NCBI
34	Lin VC, Chou CH, Lin YC, et al: Osthole suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt/mTOR pathway. J Agric Food Chem. 58:4786–4793. 2010. View Article : Google Scholar : PubMed/NCBI
35	Deng R, Tang J, Xie BF, et al: SYUNZ-16, a newly synthesized alkannin derivative, induces tumor cells apoptosis and suppresses tumor growth through inhibition of PKB/AKT kinase activity and blockade of AKT/FOXO signal pathway. Int J Cancer. 127:220–229. 2010. View Article : Google Scholar
36	Shen JK, Du HP, Yang M, Wang YG and Jin J: Casticin induces leukemic cell death through apoptosis and mitotic catastrophe. Ann Hematol. 88:743–752. 2009. View Article : Google Scholar : PubMed/NCBI
37	Jin CY, Kim GY and Choi YH: Induction of apoptosis by aqueous extract of Cordyceps militaris through activation of caspases and inactivation of Akt in human breast cancer MDA-MB-231 cells. J Microbiol Biotechnol. 18:1997–2003. 2008.
38	Chiang PC, Lin SC, Pan SL, et al: Antroquinonol displays anticancer potential against human hepatocellular carcinoma cells: a crucial role of AMPK and mTOR pathways. Biochem Pharmacol. 79:162–171. 2010. View Article : Google Scholar : PubMed/NCBI
39	Yang CJ, Huang YJ, Wang CY, et al: Antiproliferative and antitumorigenic activity of Toona sinensis leaf extracts in lung adenocarcinoma. J Med Food. 13:54–61. 2010. View Article : Google Scholar : PubMed/NCBI
40	Mi JX, Wang GF, Wang HB, et al: Synergistic antitumoral activity and induction of apoptosis by novel pan Bcl-2 proteins inhibitor apogossypolone with adriamycin in human hepatocellular carcinoma. Acta Pharmacol Sin. 29:1467–1477. 2008. View Article : Google Scholar : PubMed/NCBI
41	Wang N, Tang LJ, Zhu GQ, et al: Apoptosis induced by baicalin involving up-regulation of P53 and bax in MCF-7 cells. J Asian Nat Prod Res. 10:1129–1135. 2008. View Article : Google Scholar : PubMed/NCBI
42	Kim DW, Ahan SH and Kim TY: Enhancement of arsenic trioxide (As₂O₃)-mediated apoptosis using berberine in human neuroblastoma SH-SY5Y cells. J Korean Neurosurg Soc. 42:392–399. 2007.PubMed/NCBI
43	Su CL, Lin TY, Lin CN and Won SJ: Involvement of caspases and apoptosis-inducing factor in bufotalin-induced apoptosis of Hep 3B cells. J Agric Food Chem. 57:55–61. 2009. View Article : Google Scholar : PubMed/NCBI
44	Xie H, Qin YX, Zhou YL, et al: GA3, a new gambogic acid derivative, exhibits potent antitumor activities in vitro via apoptosis-involved mechanisms. Acta Pharmacol Sin. 30:346–354. 2009. View Article : Google Scholar : PubMed/NCBI
45	Xu X, Liu Y, Wang L, et al: Gambogic acid induces apoptosis by regulating the expression of Bax and Bcl-2 and enhancing caspase-3 activity in human malignant melanoma A375 cells. Int J Dermatol. 48:186–192. 2009. View Article : Google Scholar : PubMed/NCBI
46	Li DD, Wu XQ, Tang J, Wei XY and Zhu XF: ON-III inhibits erbB-2 tyrosine kinase receptor signal pathway and triggers apoptosis through induction of Bim in breast cancer cells. Cancer Biol Ther. 8:739–743. 2009. View Article : Google Scholar : PubMed/NCBI
47	Lai WW, Yang JS, Lai KC, et al: Rhein induced apoptosis through the endoplasmic reticulum stress, caspase- and mitochondria-dependent pathways in SCC-4 human tongue squamous cancer cells. In Vivo. 23:309–316. 2009.
48	Xiao X, Bai P, Bui Nguyen TM, et al: The antitumoral effect of Paris Saponin I associated with the induction of apoptosis through the mitochondrial pathway. Mol Cancer Ther. 8:1179–1188. 2009. View Article : Google Scholar : PubMed/NCBI
49	Xu Y, Ge R, Du J, et al: Corosolic acid induces apoptosis through mitochondrial pathway and caspase activation in human cervix adenocarcinoma HeLa cells. Cancer Lett. 284:229–237. 2009. View Article : Google Scholar : PubMed/NCBI
50	Yang HL, Chen SC, Chen CS, Wang SY and Hseu YC: Alpinia pricei rhizome extracts induce apoptosis of human carcinoma KB cells via a mitochondria-dependent apoptotic pathway. Food Chem Toxicol. 46:3318–3324. 2008. View Article : Google Scholar
51	Qi F, Li A, Zhao L, et al: Cinobufacini, an aqueous extract from Bufo bufo gargarizans Cantor, induces apoptosis through a mitochondria-mediated pathway in human hepatocellular carcinoma cells. J Ethnopharmacol. 128:654–661. 2010.PubMed/NCBI
52	Tang YJ, Yang JS, Lin CF, et al: Houttuynia cordata Thunb extract induces apoptosis through mitochondrial-dependent pathway in HT-29 human colon adenocarcinoma cells. Oncol Rep. 22:1051–1056. 2009.
53	Lu YY, Chen TS, Qu JL, Pan WL, Sun L and Wei XB: Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. J Biomed Sci. 16:162009. View Article : Google Scholar : PubMed/NCBI
54	Chen CA, Chang HH, Kao CY, Tsai TH and Chen YJ: Plumbagin, isolated from Plumbago zeylanica, induces cell death through apoptosis in human pancreatic cancer cells. Pancreatology. 9:797–809. 2009.
55	Kim HG, Song H, Yoon DH, et al: Cordyceps pruinosa extracts induce apoptosis of HeLa cells by a caspase dependent pathway. J Ethnopharmacol. 128:342–351. 2010. View Article : Google Scholar
56	Efferth T, Giaisi M, Merling A, Krammer PH and Li-Weber M: Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells. PLoS One. 2:e6932007. View Article : Google Scholar : PubMed/NCBI
57	Wu F, Hu Y, Long J, et al: Cytotoxicity and radiosensitization effect of TRA-8 on radioresistant human larynx squamous carcinoma cells. Oncol Rep. 21:461–465. 2009.PubMed/NCBI
58	Ortiz T, Burguillos MA, Lopez-Lluch G, et al: Enhanced induction of apoptosis in a radio-resistant bladder tumor cell line by combined treatments with X-rays and wortmannin. Radiat Environ Biophys. 47:445–452. 2008. View Article : Google Scholar : PubMed/NCBI
59	Du XL, Jiang T, Wen ZQ, Gao R, Cui M and Wang F: Silencing of heat shock protein 70 expression enhances radiotherapy efficacy and inhibits cell invasion in endometrial cancer cell line. Croat Med J. 50:143–150. 2009. View Article : Google Scholar : PubMed/NCBI
60	Efimova EV, Liang H, Pitroda SP, et al: Radioresistance of Stat1 over-expressing tumour cells is associated with suppressed apoptotic response to cytotoxic agents and increased IL6-IL8 signalling. Int J Radiat Biol. 85:421–431. 2009. View Article : Google Scholar : PubMed/NCBI
61	Chiou SH, Kao CL, Chen YW, et al: Identification of CD133-positive radioresistant cells in atypical teratoid/rhabdoid tumor. PLoS One. 3:e20902008. View Article : Google Scholar : PubMed/NCBI
62	Guoan X, Hanning W, Kaiyun C and Hao L: Adenovirus-mediated siRNA targeting Mcl-1 gene increases radiosensitivity of pancreatic carcinoma cells in vitro and in vivo. Surgery. 147:553–561. 2010. View Article : Google Scholar : PubMed/NCBI
63	Hara T, Omura-Minamisawa M, Kang Y, Cheng C and Inoue T: Flavopiridol potentiates the cytotoxic effects of radiation in radioresistant tumor cells in which p53 is mutated or Bcl-2 is overexpressed. Int J Radiat Oncol Biol Phys. 71:1485–1495. 2008. View Article : Google Scholar : PubMed/NCBI
64	Ezekwudo D, Shashidharamurthy R, Devineni D, Bozeman E, Palaniappan R and Selvaraj P: Inhibition of expression of anti-apoptotic protein Bcl-2 and induction of cell death in radio-resistant human prostate adenocarcinoma cell line (PC-3) by methyl jasmonate. Cancer Lett. 270:277–285. 2008. View Article : Google Scholar : PubMed/NCBI
65	Wang TJ, Liu ZS, Zeng ZC, et al: Caffeine enhances radiosensitization to orthotopic transplant LM3 hepatocellular carcinoma in vivo. Cancer Sci. 101:1440–1446. 2010. View Article : Google Scholar : PubMed/NCBI
66	You ZY, Zhao Y, Liu F, Zhang YD and Wang JJ: The radiosensitization effects of Endostar on human lung squamous cancer cells H-520. Cancer Cell Int. 10:172010. View Article : Google Scholar
67	Che SM, Zhang XZ, Hou L and Song TB: Cyclooxygenase-2 inhibitor NS398 enhances radiosensitivity of radioresistant esophageal cancer cells by inhibiting AKT activation and inducing apoptosis. Cancer Invest. 28:679–688. 2010. View Article : Google Scholar : PubMed/NCBI
68	Liu J, Zhang J, Wang X, et al: HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells. Exp Cell Res. 316:1985–1993. 2010. View Article : Google Scholar : PubMed/NCBI
69	Gao L, Li F, Dong B, et al: Inhibition of STAT3 and ErbB2 suppresses tumor growth, enhances radiosensitivity, and induces mitochondria-dependent apoptosis in glioma cells. Int J Radiat Oncol Biol Phys. 77:1223–1231. 2010. View Article : Google Scholar : PubMed/NCBI
70	Chen X, Wong P, Radany E and Wong JY: HDAC inhibitor, valproic acid, induces p53-dependent radiosensitization of colon cancer cells. Cancer Biother Radiopharm. 24:689–699. 2009. View Article : Google Scholar : PubMed/NCBI
71	Yu J and Zhang L: PUMA, a potent killer with or without p53. Oncogene. 27(Suppl 1): S71–S83. 2008. View Article : Google Scholar : PubMed/NCBI
72	Mi J, Bolesta E, Brautigan DL and Larner JM: PP2A regulates ionizing radiation-induced apoptosis through Ser46 phosphorylation of p53. Mol Cancer Ther. 8:135–140. 2009. View Article : Google Scholar : PubMed/NCBI
73	Wang R, Lin F, Wang X, et al: Suppression of Bcl-xL expression by a novel tumor-specific RNA interference system inhibits proliferation and enhances radiosensitivity in prostatic carcinoma cells. Cancer Chemother Pharmacol. 61:943–952. 2008. View Article : Google Scholar
74	Ho SY, Chen WC, Chiu HW, Lai CS, Guo HR and Wang YJ: Combination treatment with arsenic trioxide and irradiation enhances apoptotic effects in U937 cells through increased mitotic arrest and ROS generation. Chem Biol Interact. 179:304–313. 2009. View Article : Google Scholar
75	Lee TK, Johnke RM, Allison RR, O’Brien KF and Dobbs LJ Jr: Radioprotective potential of ginseng. Mutagenesis. 20:237–243. 2005. View Article : Google Scholar : PubMed/NCBI
76	Rubinsztein DC, DiFiglia M, Heintz N, et al: Autophagy and its possible roles in nervous system diseases, damage and repair. Autophagy. 1:11–22. 2005. View Article : Google Scholar : PubMed/NCBI
77	Adi-Harel S, Erlich S, Schmukler E, et al: Beclin 1 self-association is independent of autophagy induction by amino acid deprivation and rapamycin treatment. J Cell Biochem. 110:1262–1271. 2010. View Article : Google Scholar : PubMed/NCBI
78	Maiuri MC, Criollo A and Kroemer G: Crosstalk between apoptosis and autophagy within the Beclin 1 interactome. EMBO J. 29:515–516. 2010. View Article : Google Scholar : PubMed/NCBI
79	Pimkina J, Humbey O, Zilfou JT, Jarnik M and Murphy ME: ARF induces autophagy by virtue of interaction with Bcl-xl. J Biol Chem. 284:2803–2810. 2009. View Article : Google Scholar : PubMed/NCBI
80	Moretti L, Attia A, Kim KW and Lu B: Crosstalk between Bak/Bax and mTOR signaling regulates radiation-induced autophagy. Autophagy. 3:142–144. 2007. View Article : Google Scholar : PubMed/NCBI
81	Zalckvar E, Berissi H, Mizrachy L, et al: DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. EMBO Rep. 10:285–292. 2009. View Article : Google Scholar : PubMed/NCBI
82	Thyagarajan A, Jedinak A, Nguyen H, et al: Triterpenes from Ganoderma lucidum induce autophagy in colon cancer through the inhibition of p38 mitogen-activated kinase (p38 MAPK). Nutr Cancer. 62:630–640. 2010.
83	Bui-Xuan NH, Tang PM, Wong CK and Fung KP: Photo-activated pheophorbide-a, an active component of Scutellaria barbata, enhances apoptosis via the suppression of ERK-mediated autophagy in the estrogen receptor-negative human breast adenocarcinoma cells MDA-MB-231. J Ethnopharmacol. 131:95–103. 2010.PubMed/NCBI
84	Kuo YF, Su YZ, Tseng YH, Wang SY, Wang HM and Chueh PJ: Flavokawain B, a novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: Involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells. Free Radic Biol Med. 49:214–226. 2010.PubMed/NCBI
85	Yo YT, Shieh GS, Hsu KF, Wu CL and Shiau AL: Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway. J Agric Food Chem. 57:8266–8273. 2009. View Article : Google Scholar : PubMed/NCBI
86	Law BY, Wang M, Ma DL, et al: Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis. Mol Cancer Ther. 9:718–730. 2010. View Article : Google Scholar : PubMed/NCBI
87	Kim KW, Hwang M, Moretti L, Jaboin JJ, Cha YI and Lu B: Autophagy upregulation by inhibitors of caspase-3 and mTOR enhances radiotherapy in a mouse model of lung cancer. Autophagy. 4:659–668. 2008. View Article : Google Scholar : PubMed/NCBI
88	Kim KW, Moretti L, Mitchell LR, Jung DK and Lu B: Combined Bcl-2/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model. Clin Cancer Res. 15:6096–6105. 2009. View Article : Google Scholar : PubMed/NCBI