Anisi stellati fructus extract attenuates the in vitro and in vivo metastatic and angiogenic potential of malignant cancer cells by downregulating proteolytic activity and pro-angiogenic factors

Kim,Aeyung; Im,Minju; Ma,Jin  Yeul

doi:10.3892/ijo.2014.2606

Anisi stellati fructus extract attenuates the in vitro and in vivo metastatic and angiogenic potential of malignant cancer cells by downregulating proteolytic activity and pro-angiogenic factors

Authors:
- Aeyung Kim
- Minju Im
- Jin Yeul Ma
View Affiliations

Affiliations: Korean Medicine (KM)-Based Herbal Drug Development Center, Korea Institute of Oriental Medicine (KIOM), Daejeon 305-811, Republic of Korea
Published online on: August 18, 2014 https://doi.org/10.3892/ijo.2014.2606
Pages: 1937-1948

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Anisi stellati fructus (ASF), commonly known as star anise, has long been used as a traditional Chinese medicine to treat inflammation, nervousness, insomnia and pain. In recent studies, it has been demonstrated that ASF possesses anti-bacterial, anti-fungal and anti-oxidant activities, as well as exhibits inhibitory effects on capillary‑like tube formation in human umbilical vein endothelial cells (HUVECs). However, the effects of ASF extract on the metastatic potential of malignant tumor cells have not been examined. In this study, we found that daily oral administration of ASF (50 mg/kg) remarkably reduced the number of pulmonary metastatic colonies of B16F10 cells in C57BL/6J mice with no observed systemic toxicity. In an in vitro system, ASF inhibited metastatic properties, including anchorage‑independent colony formation, migration and invasion. Upon phorbol 12-myristate 13-acetate (PMA) stimulation, the mRNA levels of matrix metalloproteinases (MMPs) -9, -13, -14 and urokinase plasminogen activator (uPA) decreased in a dose-dependent manner with ASF treatment. Gelatinase, type I collagenase, and uPA activities were also suppressed efficiently by ASF treatment. In response to PMA, NF-κB and AP-1 activation as well as p38 phosphorylation, which are crucial for MMP activation, were significantly decreased by ASF. In particular, ASF considerably inhibited tumor-induced HUVEC migration and tube formation and suppressed in vivo tumor-induced angiogenesis via a reduction of pro-angiogenic factors in tumors. These results collectively indicate that ASF might be useful in the management of metastatic malignant tumors.

View Figures

View References

1	Liotta LA, Steeg PS and Stetler-Stevenson WG: Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 64:327–336. 1991. View Article : Google Scholar : PubMed/NCBI
2	Patel LR, Camacho DF, Shiozawa Y, Pienta KJ and Taichman RS: Mechanisms of cancer cell metastasis to the bone: a multistep process. Future Oncol. 7:1285–1297. 2011. View Article : Google Scholar : PubMed/NCBI
3	Deryugina EI and Quigley JP: Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 25:9–34. 2006. View Article : Google Scholar
4	Westermarck J and Kahari VM: Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 13:781–792. 1999.PubMed/NCBI
5	Gondi CS, Lakka SS, Dinh DH, Olivero WC, Gujrati M and Rao JS: Downregulation of uPA, uPAR and MMP-9 using small, interfering, hairpin RNA (siRNA) inhibits glioma cell invasion, angiogenesis and tumor growth. Neuron Glia Biol. 1:165–176. 2004. View Article : Google Scholar : PubMed/NCBI
6	Lockhart AC, Braun RD, Yu D, et al: Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor. Clin Cancer Res. 9:586–593. 2003.
7	Zheng H, Takahashi H, Murai Y, et al: Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res. 26:3579–3583. 2006.PubMed/NCBI
8	Folkman J: Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 29:15–18. 2002. View Article : Google Scholar : PubMed/NCBI
9	Bicknell R: Vascular targeting and the inhibition of angiogenesis. Ann Oncol Suppl. 4:45–50. 1994. View Article : Google Scholar : PubMed/NCBI
10	Appelmann I, Liersch R, Kessler T, Mesters RM and Berdel WE: Angiogenesis inhibition in cancer therapy: platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) and their receptors: biological functions and role in malignancy. Recent Results Cancer Res. 180:51–81. 2010. View Article : Google Scholar
11	Poveshchenko AF and Konenkov VI: Mechanisms and factors of angiogenesis. Usp Fiziol Nauk. 41:68–89. 2010.(In Russian).
12	Wang GW, Hu WT, Huang BK and Qin LP: Illicium verum: a review on its botany, traditional use, chemistry and pharmacology. J Ethnopharmacol. 136:10–20. 2011. View Article : Google Scholar
13	Ghosh S, Chisti Y and Banerjee UC: Production of shikimic acid. Biotechnol Adv. 30:1425–1431. 2012. View Article : Google Scholar
14	Huang Y, Zhao J, Zhou L, et al: Antifungal activity of the essential oil of Illicium verum fruit and its main component trans-anethole. Molecules. 15:7558–7569. 2010.PubMed/NCBI
15	Bhadra S, Mukherjee PK, Kumar NS and Bandyopadhyay A: Anticholinesterase activity of standardized extract of Illicium verum Hook. f. fruits. Fitoterapia. 82:342–346. 2011. View Article : Google Scholar : PubMed/NCBI
16	Nam NH, Kim HM, Bae KH and Ahn BZ: Inhibitory effects of Vietnamese medicinal plants on tube-like formation of human umbilical venous cells. Phytother Res. 17:107–111. 2003. View Article : Google Scholar : PubMed/NCBI
17	Kim A, Im M, Yim NH, Jung YP and Ma JY: Aqueous extract of Bambusae Caulis in Taeniam inhibits PMA-induced tumor cell invasion and pulmonary metastasis: suppression of NF-kappaB activation through ROS signaling. PLoS One. 8:e780612013.
18	Kim A, Kim MJ, Yang Y, Kim JW, Yeom YI and Lim JS: Suppression of NF-kappaB activity by NDRG2 expression attenuates the invasive potential of highly malignant tumor cells. Carcinogenesis. 30:927–936. 2009. View Article : Google Scholar : PubMed/NCBI
19	Cho HJ, Kang JH, Kwak JY, et al: Ascofuranone suppresses PMA-mediated matrix metalloproteinase-9 gene activation through the Ras/Raf/MEK/ERK- and Ap1-dependent mechanisms. Carcinogenesis. 28:1104–1110. 2007. View Article : Google Scholar : PubMed/NCBI
20	Sato T, Koike L, Miyata Y, et al: Inhibition of activator protein-1 binding activity and phosphatidylinositol 3-kinase pathway by nobiletin, a polymethoxy flavonoid, results in augmentation of tissue inhibitor of metalloproteinases-1 production and suppression of production of matrix metalloproteinases-1 and -9 in human fibrosarcoma HT-1080 cells. Cancer Res. 62:1025–1029. 2002.
21	Choi JH, Han EH, Hwang YP, et al: Suppression of PMA-induced tumor cell invasion and metastasis by aqueous extract isolated from Prunella vulgaris via the inhibition of NF-kappaB-dependent MMP-9 expression. Food Chem Toxicol. 48:564–571. 2010. View Article : Google Scholar : PubMed/NCBI
22	Hwang YP, Yun HJ, Kim HG, Han EH, Lee GW and Jeong HG: Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms. Biochem Pharmacol. 79:1714–1726. 2010. View Article : Google Scholar : PubMed/NCBI
23	Fang J, Zhou Q, Liu LZ, et al: Apigenin inhibits tumor angiogenesis through decreasing HIF-1alpha and VEGF expression. Carcinogenesis. 28:858–864. 2007. View Article : Google Scholar : PubMed/NCBI
24	Wang Z, Wang L, Li T, et al: Rapid analysis of the essential oils from dried Illicium verum Hook. f and Zingiber officinale Rosc by improved solvent-free microwave extraction with three types of microwave-absorption medium. Anal Bioanal Chem. 386:1863–1868. 2006.PubMed/NCBI
25	Yang JF, Yang CH, Chang HW, et al: Chemical composition and antibacterial activities of Illicium verum against antibiotic-resistant pathogens. J Med Food. 13:1254–1262. 2010. View Article : Google Scholar : PubMed/NCBI
26	Iauk L, Lo Bue AM, Milazzo I, Rapisarda A and Blandino G: Antibacterial activity of medicinal plant extracts against periodontopathic bacteria. Phytother Res. 17:599–604. 2003. View Article : Google Scholar : PubMed/NCBI
27	Guo DJ, Cheng HL, Chan SW and Yu PH: Antioxidative activities and the total phenolic contents of tonic Chinese medicinal herbs. Inflammopharmacology. 16:201–207. 2008. View Article : Google Scholar : PubMed/NCBI
28	Nakamura T, Okuyama E and Yamazaki M: Neurotropic components from star anise (Illicium verum Hook. fil.). Chem Pharm Bull. 44:1908–1914. 1996. View Article : Google Scholar
29	Okuyama E, Nakamura T and Yamazaki M: Convulsants from star anise (Illicium verum Hook. F.). Chem Pharm Bull. 41:1670–1671. 1993. View Article : Google Scholar : PubMed/NCBI
30	Mira E, Lacalle RA, Buesa JM, et al: Secreted MMP9 promotes angiogenesis more efficiently than constitutive active MMP9 bound to the tumor cell surface. J Cell Sci. 117:1847–1857. 2004. View Article : Google Scholar : PubMed/NCBI
31	Lee SO, Jeong YJ, Yu MH, et al: Wogonin suppresses TNF-alpha-induced MMP-9 expression by blocking the NF-kappaB activation via MAPK signaling pathways in human aortic smooth muscle cells. Biochem Biophys Res Commun. 351:118–125. 2006. View Article : Google Scholar : PubMed/NCBI
32	Lubet RA, Steele VE, Eto I, Juliana MM, Kelloff GJ and Grubbs CJ: Chemopreventive efficacy of anethole trithione, N-acetyl-L-cysteine, miconazole and phenethylisothiocyanate in the DMBA-induced rat mammary cancer model. I J Cancer. 72:95–101. 1997.PubMed/NCBI
33	Choo EJ, Rhee YH, Jeong SJ, et al: Anethole exerts antimetatstaic activity via inhibition of matrix metalloproteinase 2/9 and AKT/mitogen-activated kinase/nuclear factor kappa B signaling pathways. Biol Pharm Bull. 34:41–46. 2011. View Article : Google Scholar