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Article

Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro

  • Authors:
    • Zhi-Zhong Zheng
    • Yan-Lin Ming
    • Liang-Hua Chen
    • Guo-Hua Zheng
    • Shao-Song Liu
    • Qing-Xi Chen
  • View Affiliations / Copyright

    Affiliations: The Research and Development Center for Medicine Plant and Plant Drugs, Xiamen Overseas Chinese Subtropical Plant Introduction Garden, Xiamen, Fujian 361002, P.R. China, Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China
  • Pages: 325-331
    |
    Published online on: May 8, 2014
       https://doi.org/10.3892/or.2014.3171
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Abstract

An intestinal bacterial metabolite of ginseng protopanaxadiol saponin, 20-O-(β-D-glucopyranosyl)-20(S)-protopanaxadiol (compound K), has been reported to induce apoptosis in a variety of cancer cells. However, the precise mechanisms induced by compound K in human hepatocellular carcinoma (HCC) cells remain unclear. In order to examine possible apoptotic mechanisms, we investigated the anticancer effect of compound K in MHCC97-H. MTT assay showed that compound K inhibited the proliferation of MHCC97-H cells with a relatively low toxicity in normal hepatoma cells. Cell cycle progression and cell staining showed an increase in apoptotic sub-G1 fraction. Treatment of MHCC97-H with compound K also induced a reduction in mitochondrial membrane potential (Δψm) and DNA damage. Further study showed that compound K upregulated Fas, FasL, Bax/Bcl-2 ratio and downregulated pro-caspase-9, pro-caspase-3 in a dose-dependent manner, and it also inhibited Akt phosphorylation. These results suggest that compound K significantly inhibits cell proliferation and induces apoptosis in MHCC97-H cells through Fas- and mitochondria-mediated caspase-dependent pathways in human HCC cells.
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1 

Parkin DM, Bray F, Ferlay J and Pisani P: Estimating the world cancer burden: Globocan 2000. Int J Cancer. 94:153–156. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Ogunbiyi JO: Hepatocellular carcinoma in the developing world. Semin Oncol. 28:179–187. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Cotter TG: Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer. 9:501–507. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Choi HH, Jong HS, Park JH, et al: A novel ginseng saponin metabolite induces apoptosis and down-regulates fibroblast growth factor receptor 3 in myeloma cells. Int J Oncol. 23:1087–1093. 2003.PubMed/NCBI

5 

Hu C, Song G, Zhang B, Liu Z, Chen R, Zhang H and Hu T: Intestinal metabolite compound K of panaxoside inhibits the growth of gastric carcinoma by augmenting apoptosis via Bid-mediated mitochondrial pathway. J Cell Mol Med. 16:96–106. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Attele AS, Wu JA and Yuan CS: Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 58:1685–1693. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Joh EH, Lee IA, Jung IH and Kim DH: Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation - the key step of inflammation. Biochem Pharmacol. 82:278–286. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Kobashi K and Akao T: Relation of intestinal bacteria to pharmacological effects of glycosides. Bioscience Microflora. 16:1–7. 1997. View Article : Google Scholar

9 

Wakabayashi C, Hasegawa H, Murata J and Saiki I: The expression of in vivo antimetastatic effect of ginseng protopanaxatriol saponins is mediated by their intestinal bacterial metabolites after oral administration. J Traditional Med. 14:180–185. 1997.

10 

Wakabayashi C, Hasegawa H, Murata J and Saiki I: In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration. Oncol Res. 9:411–417. 1997.

11 

Akao T, Kanaoka M and Kobashi K: Appearance of compound K, a major metabolite of ginsenoside Rb1 by intestinal bacteria, in rat plasma after oral administration - measurement of compound K by enzyme immunoassay. Biol Pharm Bull. 21:245–249. 1998. View Article : Google Scholar

12 

Wang CZ, Kim KE, Du GJ, et al: Ultra-performance liquid chromatography and time-of-flight mass spectrometry analysis of ginsenoside metabolites in human plasma. Am J Chin Med. 39:1161–1171. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Tsutsumi YM, Tsutsumi R, Mawatari K, Nakaya Y, Kinoshita M, Tanaka K and Oshita S: Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway. Life Sci. 88:725–729. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Choo MK, Sakurai H, Kim DH and Saiki I: A ginseng saponin metabolite suppresses tumor necrosis factor-α-promoted metastasis by suppressing nuclear factor-κB signaling in murine colon cancer cells. Oncol Rep. 19:595–600. 2008.PubMed/NCBI

15 

Kim DY, Yuan HD, Chung IK and Chung SH: Compound K, intestinal metabolite of ginsenoside, attenuates hepatic lipid accumulation via AMPK activation in human hepatoma cells. J Agric Food Chem. 57:1532–1537. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Lee BH, Lee SJ, Hur JH, Lee S, Sung JH, Huh JD and Moon CK: In vitro antigenotoxic activity of novel ginseng saponin metabolites formed by intestinal bacteria. Planta Med. 64:500–503. 1998. View Article : Google Scholar

17 

Lee SJ, Sung JH, Lee SJ, Moon CK and Lee BH: Antitumor activity of a novel ginseng saponin metabolite in human pulmonary adenocarcinoma cells resistant to cisplatin. Cancer Lett. 144:39–43. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Hasegawa H, Sung JH, Matsumiya S, Uchiyama M, Inouye Y, Kasai R and Yamasaki K: Reversal of daunomycin and vinblastine resistance in multidrug-resistant P388 leukemia in vitro through enhanced cytotoxicity by triterpenoids. Planta Med. 61:409–413. 1995. View Article : Google Scholar : PubMed/NCBI

19 

Ming YL, Song G, Chen LH, et al: Anti-proliferation and apoptosis induced by a novel intestinal metabolite of ginseng saponin in human hepatocellular carcinoma cells. Cell Biol Int. 31:1265–1273. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Cossarizza A, Baccarani-Contri M, Kalashnikova G and Franceschi C: A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun. 197:40–45. 1993.PubMed/NCBI

21 

Collins AR, Dobson VL, Dusinska M, Kennedy G and Stetina R: The comet assay: what can it really tell us? Mutat Res. 375:183–193. 1997. View Article : Google Scholar : PubMed/NCBI

22 

Panayiotidis M, Tsolas O and Galaris D: Glucose oxidase-produced H2O2 induces Ca2+-dependent DNA damage in human peripheral blood lymphocytes. Free Radic Biol Med. 26:548–556. 1999.

23 

Hasegawa H: Proof of the mysterious efficacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid. J Pharmacol Sci. 95:153–157. 2004. View Article : Google Scholar

24 

Lee JY, Shin JW, Chun KS, et al: Antitumor promotional effects of a novel intestinal bacterial metabolite (IH-901) derived from the protopanaxadiol-type ginsenosides in mouse skin. Carcinogenesis. 26:359–367. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Ming YL, Zheng ZZ, Chen LH and Tong QX: Apoptosis induced by a novel intestinal metabolite of ginseng saponin in human hepatocellular carcinoma BEL-7402 cells. Chin Trad Herbal Drugs. 38:1511–1514. 2007.

26 

Qi F, Li A, Inagaki Y, et al: Induction of apoptosis by cinobufacini preparation through mitochondria- and Fas-mediated caspase-dependent pathways in human hepatocellular carcinoma cells. Food Chem Toxicol. 50:295–302. 2012. View Article : Google Scholar

27 

Vaithinathan S, Saradha B and Mathur PP: Methoxychlor induces apoptosis via mitochondria- and FasL-mediated pathways in adult rat testis. Chem Biol Interact. 185:110–118. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Nagata S: Fas ligand-induced apoptosis. Annu Rev Genet. 33:29–55. 1999. View Article : Google Scholar

29 

Schug ZT, Gonzalvez F, Houtkooper RH, Vaz FM and Gottlieb E: BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death Differ. 18:538–548. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Medema JP, Scaffidi C, Kischkel FC, Shevchenko A, Mann M, Krammer PH and Peter ME: FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J. 16:2794–2804. 1997. View Article : Google Scholar : PubMed/NCBI

31 

Herr I and Debatin KM: Cellular stress response and apoptosis in cancer therapy. Blood. 98:2603–2614. 2001. View Article : Google Scholar : PubMed/NCBI

32 

Liu X, Kim CN, Yang J, Jemmerson R and Wang X: Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 86:147–157. 1996. View Article : Google Scholar : PubMed/NCBI

33 

Srinivasula SM, Ahmad M, Fernandes-Alnemri T and Alnemri ES: Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. Mol Cell. 1:949–957. 1998. View Article : Google Scholar : PubMed/NCBI

34 

Slee EA, Harte MT, Kluck RM, et al: Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol. 144:281–292. 1999. View Article : Google Scholar : PubMed/NCBI

35 

Jeong SJ, Dasgupta A, Jung KJ, Um JH, Burke A, Park HU and Brady JN: PI3K/AKT inhibition induces caspase-dependent apoptosis in HTLV-1-transformed cells. Virology. 370:264–272. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Moon DO, Park SY, Choi YH, Kim ND, Lee C and Kim GY: Melittin induces Bcl-2 and caspase-3-dependent apoptosis through downregulation of Akt phosphorylation in human leukemic U937 cells. Toxicon. 51:112–120. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Oh SH, Yin HQ and Lee BH: Role of the Fas/Fas ligand death receptor pathway in ginseng saponin metabolite-induced apoptosis in HepG2 cells. Arch Pharm Res. 27:402–406. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zheng Z, Ming Y, Chen L, Zheng G, Liu S and Chen Q: Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro. Oncol Rep 32: 325-331, 2014.
APA
Zheng, Z., Ming, Y., Chen, L., Zheng, G., Liu, S., & Chen, Q. (2014). Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro. Oncology Reports, 32, 325-331. https://doi.org/10.3892/or.2014.3171
MLA
Zheng, Z., Ming, Y., Chen, L., Zheng, G., Liu, S., Chen, Q."Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro". Oncology Reports 32.1 (2014): 325-331.
Chicago
Zheng, Z., Ming, Y., Chen, L., Zheng, G., Liu, S., Chen, Q."Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro". Oncology Reports 32, no. 1 (2014): 325-331. https://doi.org/10.3892/or.2014.3171
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng Z, Ming Y, Chen L, Zheng G, Liu S and Chen Q: Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro. Oncol Rep 32: 325-331, 2014.
APA
Zheng, Z., Ming, Y., Chen, L., Zheng, G., Liu, S., & Chen, Q. (2014). Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro. Oncology Reports, 32, 325-331. https://doi.org/10.3892/or.2014.3171
MLA
Zheng, Z., Ming, Y., Chen, L., Zheng, G., Liu, S., Chen, Q."Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro". Oncology Reports 32.1 (2014): 325-331.
Chicago
Zheng, Z., Ming, Y., Chen, L., Zheng, G., Liu, S., Chen, Q."Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro". Oncology Reports 32, no. 1 (2014): 325-331. https://doi.org/10.3892/or.2014.3171
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