Corilagin induces the apoptosis of hepatocellular carcinoma cells through the mitochondrial apoptotic and death receptor pathways

Deng,Yuan; Li,Xudan; Li,Xuan; Zheng,Zhizhong; Huang,Wen; Chen,Lianghua; Tong,Qingxuan; Ming,Yanlin

doi:10.3892/or.2018.6396

Corilagin induces the apoptosis of hepatocellular carcinoma cells through the mitochondrial apoptotic and death receptor pathways

Authors:
- Yuan Deng
- Xudan Li
- Xuan Li
- Zhizhong Zheng
- Wen Huang
- Lianghua Chen
- Qingxuan Tong
- Yanlin Ming
View Affiliations

Affiliations: Key Laboratory of Xiamen City for Plant Introduction and Quarantine and Plant Products, Xiamen Overseas Chinese Subtropical Plant Introduction Garden, Xiamen, Fujian 361002, P.R. China, Key Laboratory of Fujian Province for Physiology and Biochemistry of Subtropical Plant, Fujian Institute of Subtropical Botany, Xiamen, Fujian 361006, P.R. China
Published online on: April 23, 2018 https://doi.org/10.3892/or.2018.6396
Pages: 2545-2552
Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Corilagin, a gallotannin, is one of the major active components of many ethnopharmacological plants and exhibits antitumor, anti-inflammatory and antioxidative properties. In recent years, corilagin has provoked much attention due to its antitumor activity, yet the mechanisms attributed to its anticancer actions are largely unknown. In our previous research, our group reported that corilagin could inhibit the proliferation of hepatocellular carcinoma (HCC) cells by inducing G2/M phase arrest. In the present study, observation of the morphological changes showed that corilagin induced the apoptosis of HCC cells as determined by AO/EB and Hoechst 33258 staining assays. Furthermore, flow cytometric analysis was carried out to calculate the apoptotic rate which was 24.1% following treatment with corilagin (37.5 µM). At the molecular level, mitochondrial membrane potential assay and western blot analysis showed that the mitochondrial transmembrane potential was reduced and the rate of release of cytochrome c was increased, which led to the activation of caspase-9, caspase-3 and cleavage of PARP in the cytoplasm indicating activation of the mitochondrial apoptotic pathway. Moreover, following treatment with corilagin, we noted upregulation of Fas and FasL and activation of caspase-8 which represented activation of the death receptor pathway, and we also observed downregulation of Bcl-2 and survivin which was also attributed to the antitumor effect of corilagin. These results suggest that corilagin significantly induced the apoptosis of HCC cells through both the mitochondrial apoptotic pathway and the death receptor pathway, and corilagin is a potential complementary anticancer herbal drug for HCC therapy.

View Figures

View References

1	Singh S, Singh PP, Roberts LR and Sanchez W: Chemopreventive strategies in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 11:45–54. 2014. View Article : Google Scholar : PubMed/NCBI
2	Ming Y, Zheng Z, Chen L, Zheng G, Liu S, Yu Y and Tong Q: Corilagin inhibits hepatocellular carcinoma cell proliferation by inducing G2/M phase arrest. Cell Biol Int. 37:1046–1054. 2013. View Article : Google Scholar : PubMed/NCBI
3	Jia L, Jin H, Zhou J, Chen L, Lu Y, Ming Y and Yu Y: A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways. BMC Complement Altern Med. 13:332013. View Article : Google Scholar : PubMed/NCBI
4	Schmidt OT and Lademann R: Corilagin, ein weiterer kristallisierter Gerbstoff aus Dividivi. X. Mitteilung über natürliche Gerbstoffe. Justus Liebigs Ann Chem. 571:232–237. 1951.(In German). View Article : Google Scholar
5	Pham AT, Malterud KE, Paulsen BS, Diallo D and Wangensteen H: DPPH radical scavenging and xanthine oxidase inhibitory activity of Terminalia macroptera leaves. Nat Prod Commun. 6:1125–1128. 2011.PubMed/NCBI
6	Yang F, Wang Y, Xue J, Ma Q, Zhang J, Chen YF, Shang ZZ, Li QQ, Zhang SL and Zhao L: Effect of Corilagin on the miR-21/smad7/ERK signaling pathway in a schistosomiasis-induced hepatic fibrosis mouse model. Parasitol Int. 65:308–315. 2016. View Article : Google Scholar : PubMed/NCBI
7	Dong XR, Luo M, Fan L, Zhang T, Liu L, Dong JH and Wu G: Corilagin inhibits the double strand break-triggered NF-kappaB pathway in irradiated microglial cells. Int J Mol Med. 25:531–536. 2010.PubMed/NCBI
8	Park JH, Joo HS, Yoo KY, Shin BN, Kim IH, Lee CH, Choi JH, Byun K, Lee B, Lim SS, et al: Extract from Terminalia chebula seeds protect against experimental ischemic neuronal damage via maintaining SODs and BDNF levels. Neurochem Res. 36:2043–2050. 2011. View Article : Google Scholar : PubMed/NCBI
9	Duan W, Yu Y and Zhang L: Antiatherogenic effects of phyllanthus emblica associated with corilagin and its analogue. Yakugaku Zasshi. 125:587–591. 2005. View Article : Google Scholar : PubMed/NCBI
10	Yang MH, Vasquez Y, Ali Z, Khan IA and Khan SI: Constituents from Terminalia species increase PPARα and PPARγ levels and stimulate glucose uptake without enhancing adipocyte differentiation. J Ethnopharmacol. 149:490–498. 2013. View Article : Google Scholar : PubMed/NCBI
11	Gambari R, Hau DK, Wong WY and Chui CH: Sensitization of Hep3B hepatoma cells to cisplatin and doxorubicin by corilagin. Phytother Res. 28:781–783. 2014. View Article : Google Scholar : PubMed/NCBI
12	Wang BQ: Corilagin nanoparticle-induced apoptosis in human gastric cancer SGC-7901 cells via the mitochondrial pathway. Acta Pharmacol Sin. 34:14. 2013.
13	Kakiuchi N, Hattori M, Namba T, Nishizawa M, Yamagishi T and Okuda T: Inhibitory effect of tannins on reverse transcriptase from RNA tumor virus. J Nat Prod. 48:614–621. 1985. View Article : Google Scholar : PubMed/NCBI
14	Berry DE, MacKenzie L, Shultis EA, Chan JA and Hecht SM: Naturally occurring inhibitors of topoisomerase I mediated DNA relaxation. J Org Chem. 57:420–422. 1992. View Article : Google Scholar
15	Hecht SM, Berry DE, MacKenzie LJ, Busby RW and Nasuti CA: A strategy for identifying novel, mechanistically unique inhibitors of topoisomerase I. J Nat Prod. 55:401–413. 1992. View Article : Google Scholar : PubMed/NCBI
16	Komori A, Yatsunami J, Suganuma M, Okabe S, Abe S, Sakai A, Sasaki K and Fujiki H: Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation. Cancer Res. 53:1982–1985. 1993.PubMed/NCBI
17	Okabe S, Suganuma M, Imayoshi Y, Taniguchi S, Yoshida T and Fujiki H: New TNF-alpha releasing inhibitors, geraniin and corilagin, in leaves of Acer nikoense, Megusurino-ki. Biol Pharm Bull. 24:1145–1148. 2001. View Article : Google Scholar : PubMed/NCBI
18	Zhang YJ, Nagao T, Tanaka T, Yang CR, Okabe H and Kouno I: Antiproliferative activity of the main constituents from Phyllanthus emblica. Biol Pharm Bull. 27:251–255. 2004. View Article : Google Scholar : PubMed/NCBI
19	Liu Z, Wang D, Chen Y, Ren L, Li K and Zhang W: Experiment studies on the pharmacodynamics experiment by corilagin. Zhongliu Fangzhi Yanjiu. 29:356–358. 2002.
20	Chen Y and Ren L: Studies on the anti-cancer active constituents of matsumura leafflower (Phyllanthus matsumarae) II. Isolation and identification of polyphenolic compounds. Chin Tradit Herbal Drugs. 28:198–202. 1997.
21	Zheng ZZ, Chen LH, Liu SS, Deng Y, Zheng GH, Gu Y and Ming YL: Bioguided fraction and isolation of the antitumor components from Phyllanthus niruri L. Biomed Res Int. 2016:97292752016. View Article : Google Scholar : PubMed/NCBI
22	Jia L, Zhou J, Zhao H, Jin H, Lv M, Zhao N, Zheng Z, Lu Y, Ming Y and Yu Y: Corilagin sensitizes epithelial ovarian cancer to chemotherapy by inhibiting Snail glycolysis pathways. Oncol Rep. 38:2464–2470. 2017. View Article : Google Scholar : PubMed/NCBI
23	Chazotte B: Labeling mitochondria with JC-1. Cold Spring Harb Protoc. Sep 1–2011.(Epub ahead of print). doi: 10.1101/pdb.prot065490. View Article : Google Scholar
24	Lampson BL and Davids MS: The development and current use of BCL-2 inhibitors for the treatment of chronic lymphocytic leukemia. Curr Hematol Malig Rep. 12:11–19. 2017. View Article : Google Scholar : PubMed/NCBI
25	Shamsabadi FT, Eidgahi MR, Mehrbod P, Daneshvar N, Allaudin ZN, Yamchi A and Shahbazi M: Survivin, a promising gene for targeted cancer treatment. Asian Pac J Cancer Prev. 17:3711–3719. 2016.PubMed/NCBI
26	Coutts AS, Adams CJ and La Thangue NB: p53 ubiquitination by Mdm2: A never ending tail? DNA Repair (Amst). 8:483–490. 2009. View Article : Google Scholar : PubMed/NCBI