Patrinia scabiosaefolia induces mitochondrial-dependent apoptosis in a mouse model of colorectal cancer

Liu,Liya; Shen,Aling; Chen,Youqin; Wei,Lihui; Lin,Jiumao; Sferra,Thomas  J.; Hong,Zhenfeng; Peng,Jun

doi:10.3892/or.2013.2528

Patrinia scabiosaefolia induces mitochondrial-dependent apoptosis in a mouse model of colorectal cancer

Authors:
- Liya Liu
- Aling Shen
- Youqin Chen
- Lihui Wei
- Jiumao Lin
- Thomas J. Sferra
- Zhenfeng Hong
- Jun Peng
View Affiliations

Affiliations: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Minhou Shangjie, Fuzhou, Fujian 350122, P.R. China, Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA, Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Minhou Shangjie, Fuzhou, Fujian 350122, P.R. China
Published online on: June 7, 2013 https://doi.org/10.3892/or.2013.2528
Pages: 897-903

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

Disrupted apoptosis not only confers a survival advantage to cancer cells but also causes resistance to chemotherapies. Therefore, inducing cell apoptosis has become a promising strategy for anticancer treatment. Patrinia scabiosaefolia (PS) has long been used to clinically treat various types of malignancies including colorectal cancer (CRC). However, the precise mechanism of its tumoricidal activity remains largely unclear. Using a CRC mouse xenograft model and a human colon carcinoma cell line, HT-29, in the present study, we evaluated the antitumor activities of an ethanol extract of Patrinia scabiosaefolia (EEPS), and investigated the underlying molecular mechanisms. We found that EEPS inhibited CRC growth both in vivo and in vitro, without apparent adverse side-effects. Moreover, EEPS treatment promoted apoptosis in CRC tumor tissues and in HT-29 cells, suggesting that the inhibitory effect of EEPS on tumor growth was due to its pro-apoptotic activity. Furthermore, EEPS treatment inhibited the expression of anti-apoptotic Bcl-2 but enhanced pro-apoptotic Bax expression at both transcriptional and translational levels. Finally, EEPS induced the loss of mitochondrial membrane potential and activation of caspase-9 and -3 in HT-29 cells. Taken together, data in this study suggest that induction of cancer cell apoptosis via the mitochondrial-dependent pathway may be one of the mechanisms whereby PS exerts anticancer activity.

View Figures

View References

1	Adams JM and Cory S: The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 26:1324–1337. 2007. View Article : Google Scholar : PubMed/NCBI
2	Cory S and Adams JM: The Bcl-2 family: regulators of the cellular life-of-death switch. Nat Rev Cancer. 2:647–656. 2002. View Article : Google Scholar : PubMed/NCBI
3	Reed JC: Mechanisms of apoptosis. Am J Pathol. 157:1415–1430. 2000. View Article : Google Scholar
4	Gross A, McDonnell JM and Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911. 1999. View Article : Google Scholar : PubMed/NCBI
5	Vaux DL and Korsmeyer SJ: Cell death in development. Cell. 96:245–254. 1999. View Article : Google Scholar
6	Hsu YT, Wolter KG and Youle RJ: Cytosol-to-membrane redistribution of Bax and Bcl-X_L during apoptosis. Proc Natl Acad Sci USA. 94:3668–3672. 1997. View Article : Google Scholar : PubMed/NCBI
7	Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG and Youle RJ: Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol. 139:1281–1292. 1997. View Article : Google Scholar : PubMed/NCBI
8	Antonsson B, Montessuit S, Lauper S, Eskes R and Martinou JC: Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem J. 345:271–278. 2000. View Article : Google Scholar : PubMed/NCBI
9	Jürgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D and Reed JC: Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci USA. 95:4997–5002. 1998.PubMed/NCBI
10	Kluck RM, Bossy-Wetzel E, Green DR and Newmeyer DD: The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 275:1132–1136. 1997.PubMed/NCBI
11	Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP and Wang X: Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 275:1129–1132. 1997. View Article : Google Scholar : PubMed/NCBI
12	Thomenius MJ, Wang NS, Reineks EZ, Wang Z and Distelhorst CW: Bcl-2 on the endoplasmic reticulum regulates Bax activity by binding to BH3-only proteins. J Biol Chem. 278:6243–6250. 2003. View Article : Google Scholar : PubMed/NCBI
13	Antonsson B, Conti F, Ciavatta A, Montessuit S, Lewis S, Martinou I, Bernasconi L, Bernard A, Mermod JJ, Mazzei G, Maundrell K, Gambale F, Sadoul R and Martinou JC: Inhibition of Bax channel-forming activity by Bcl-2. Science. 277:370–372. 1997. View Article : Google Scholar : PubMed/NCBI
14	Youle RJ and Strasser A: The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 9:47–59. 2008. View Article : Google Scholar : PubMed/NCBI
15	Yip KW and Reed JC: Bcl-2 family proteins and cancer. Oncogene. 27:6398–6406. 2008. View Article : Google Scholar : PubMed/NCBI
16	Kitada S, Pedersen IM, Schimmer AD and Reed JC: Dysregulation of apoptosis genes in hematopoietic malignancies. Oncogene. 21:3459–3474. 2002. View Article : Google Scholar : PubMed/NCBI
17	Newman DJ, Cragg GM and Snader KM: The influence of natural products upon drug discovery. Nat Prod Rep. 17:215–234. 2000. View Article : Google Scholar : PubMed/NCBI
18	Gordaliza M: Natural products as leads to anticancer drugs. Clin Transl Oncol. 9:767–776. 2007. View Article : Google Scholar : PubMed/NCBI
19	Ju HK, Baek SH, An RB, Bae K, Son KH, Kim HP, Kang SS, Lee SH, Son JK and Chang HW: Inhibitory effects of nardostachin on nitric oxide, prostaglandin E₂, and tumor necrosis factor-α production in lipopolysaccharide activated macrophages. Biol Pharm Bull. 26:1375–1378. 2003. View Article : Google Scholar : PubMed/NCBI
20	Chiu LC, Ho TS, Wong EY and Ooi VE: Ethyl acetate extract of Patrinia scabiosaefolia downregulates anti-apoptotic Bcl-2/Bcl-X_L expression, and induces apoptosis in human breast carcinoma MCF-7 cells independent of caspase-9 activation. J Ethnopharmacol. 105:263–268. 2006.PubMed/NCBI
21	Peng J, Chen YQ, Lin JM, Zhuang ZQ, Xu W, Hong ZF and Sferra TJ: Patrinia scabiosaefolia extract suppresses proliferation and promotes apoptosis by inhibiting STAT3 pathway in human multiple myeloma cells. Mol Med Rep. 4:313–318. 2011.
22	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
23	Gustin DM and Brenner DE: Chemoprevention of colon cancer: current status and future prospects. Cancer Metastasis Rev. 21:323–348. 2002. View Article : Google Scholar : PubMed/NCBI
24	Gorlick R and Bertino JR: Drug resistance in colon cancer. Semin Oncol. 26:606–611. 1999.
25	Longley DB, Allen WL and Johnston PG: Drug resistance, predictive markers and pharmacogenomics in colorectal cancer. Biochim Biophys Acta. 1766:184–196. 2006.PubMed/NCBI
26	Boose G and Stopper H: Genotoxicity of several clinically used topoisomerase II inhibitors. Toxicol Lett. 116:7–16. 2000. View Article : Google Scholar : PubMed/NCBI
27	Mäntymaa P, Siitonen T, Guttorm T, Säily M, Kinnula V, Savolainen ER and Koistinen P: Induction of mitochondrial manganese superoxide dismutase confers resistance to apoptosis in acute myeloblastic leukaemia cells exposed to etoposide. Br J Haematol. 108:574–581. 2000.PubMed/NCBI
28	Körper S, Nolte F, Rojewski MT, Thiel E and Schrezenmeier H: The K⁺ channel openers diazoxide and NS1619 induce depolarization of mitochondria and have differential effects on cell Ca²⁺ in CD34⁺ cell line KG-1a. Exp Hematol. 31:815–823. 2003.