DOI QR코드

DOI QR Code

In-Jin-Ho-Tang as a potential anti-cancer drug by induction of apoptosis in HepG2 cells

  • Yun, Hyun-Jeong (Cardiovascular Medical Research Center and Department of Prescriptionology, College of Oriental Medicine, Dongguk University) ;
  • Heo, Sook-Kyoung (Cardiovascular Medical Research Center and Department of Prescriptionology, College of Oriental Medicine, Dongguk University) ;
  • Park, Won-Hwan (Cardiovascular Medical Research Center and Department of Prescriptionology, College of Oriental Medicine, Dongguk University) ;
  • Park, Sun-Dong (Cardiovascular Medical Research Center and Department of Prescriptionology, College of Oriental Medicine, Dongguk University)
  • 발행 : 2009.06.30

초록

Hepatocellular carcinoma is the world's most common primary malignant tumor of the liver. In-Jin-ho-Tang (IJHT) has been used as a traditional Chinese herbal medicine since ancient times, and today it is widely used as a medication for jaundice associated with inflammation of the liver. In-Jin-Ho-Tang is a drug preparation consisting of three herbs: Artemisiae Capillaris Herba (Artemisia capillaries $T_{HUNS}$, Injinho in Korean), Gardeniae Fructus (Gardenia jasminodes $E_{LLIS}$, Chija in Korean) and Rhei radix et rhizoma (Rheum palmatum L., Daehwang in Korean). This study investigated whether or not methanol extract of IJHT could induce HepG2 cancer cell death. Cytotoxic activity of IJHT on HepG2 cells was measured using an XTT assay, with an $IC_{50}$ value of $700{\mu}g/ml$ at 24 h Apoptosis induction by IJHT in HepG2 cells was verified by the cleavage of poly ADP-ribose polymerase, and a decrease in procaspase-3, -8, -9. Treatment of IJHT resulted in the release of cytochrome c into cytosol, loss of mitochondrial membrane potential (${\Delta}{\Psi}_m$), decrease in anti-apoptotic Bcl-2, and an increase in pro-apoptotic Bax expression. Thus, IJHT induced apoptosis in HepG2 cells via activation of caspase and mitochondria pathway. These results indicate that IJHT has potential as an anti-cancer agent.

키워드

참고문헌

  1. Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. (1999) Biochemical pathways of caspase activation during apoptosis. Annu. Rev. Cell Dev. Biol. 15, 269-290 https://doi.org/10.1146/annurev.cellbio.15.1.269
  2. Cheung CS, Chung KK, Lui JC, Lau CP, Hon PM, Chan JY, Fung KP, Au SW. (2007) Leachianone A as a potential anti-cancer drug by induction of apoptosis in human hepatoma HepG2 cells. Cancer Lett. 253, 224-235 https://doi.org/10.1016/j.canlet.2007.01.025
  3. Garland JM, Rudin C. (1998) Cytochrome c induces caspase-dependent apoptosis in intact hematopoietic cells and overrides apoptosis suppression mediated by bcl-2, growth factor signaling, MAP-kinasekinase, and malignant change. Blood 92, 1235-1246
  4. Ha KT, Kim JK, Lee YC, Kim CH. (2004a) Inhibitory effect of Daesungki-Tang on the invasiveness potential of hepatocellular carcinoma through inhibition of matrix metalloproteinase-2 and -9 activities. Toxicol. Appl. Pharmacol. 200, 1-6 https://doi.org/10.1016/j.taap.2004.03.012
  5. Ha KT, Lee TK, Kwak KH, Kim JK, Kim DI, Choi DY, Kim CH. (2004b) Inhibitory effect of Cho-Deung- San on human aortic smooth muscle cell migration induced by TNF-alpha through inhibition of matrix metalloproteinase-2 and -9 activity. Vascul. Pharmacol. 41, 83-90 https://doi.org/10.1016/j.vph.2004.05.003
  6. Huang Q, Lu G, Shen HM, Chung MC, Ong CN. (2006) Anti-cancer properties of anthraquinones from Rhubarb. Med. Res. Rev. 27, 609-630 https://doi.org/10.1002/med.20094
  7. Hur YG, Yun Y, Won J. (2004) Rosmarinic acid induces p56 lck-dependent apoptosis in Jurkat and peripheral T cells via mitochondrial pathway independent from Fas/Fas ligand interaction. J. Immunol. 172, 79-87 https://doi.org/10.4049/jimmunol.172.1.79
  8. Iinuma Y, Kubota M, Yagi M, Kanada S, Yamazaki S, Kinoshita Y. (2003) Effects of the herbal medicine Inchinko-to on liver function in postoperative patients with biliary atresia-a pilot study. J. Pediatr. Surg. 38, 1607-1611 https://doi.org/10.1016/S0022-3468(03)00570-0
  9. Inao M, Mochida S, Matsui A, Eguchi Y, Yulutuz Y, Wang Y, Naiki K, Kakinuma T, Fujimori K, Nagoshi S, Fujiwara K. (2004) Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis. J. Hepatol. 41, 584-591 https://doi.org/10.1016/j.jhep.2004.06.033
  10. Itoh T, Shibahara N, Mantani N, Tahara E, Shimada Y, Terasawa K. (1997) Effect of Kampo treatment on chronic viral hepatitis on the basis of traditional diagnosis. J. Trad. Med. 14, 204-210
  11. Lee TY, Chang HH, Chen JH, Hsueh ML, Kuo JJ. (2007) Herb medicine Yin-Chen-Hao-Tang ameliorates hepatic fibrosis in bile duct ligation rats. J. Ethnopharmacol. 109, 318-324 https://doi.org/10.1016/j.jep.2006.07.042
  12. Lee TY, Wang GJ, Chiu JH, Lin HC. (2003) Long-term administration of Salvia miltiorrhiza ameliorates the carbon tetrachloride-induced chronic hepatic fibrosis in rats. J. Pharm. Pharmacol. 55, 1561-1568 https://doi.org/10.1211/0022357022098
  13. Lin S, Fujii M, Hou DX. (2003) Rhein induces apoptosis in HL-60 cells via reactive oxygen species-independent mitochondrial death pathway. Arch. Biochem. Biophys. 418, 99-107 https://doi.org/10.1016/j.abb.2003.08.004
  14. Nowak AK, Chow PK, Findlay M. (2004) Systemic therapy for advanced hepatocellular carcinoma: a review. Eur. J .Cancer. 40, 1474-1484 https://doi.org/10.1016/j.ejca.2004.02.027
  15. Onji M, Kikuchi T, Michitaka K, Yamashita K, Ohta Y. (1990) Combined use of ursodeoxycholic acid and Inchinko-to in jaundice patients with primary biliary cirrhosis. J. Med. Pharm. Soc. Wakan-Yaku 7, 161-167
  16. Petit PX, Zamzami N, Vayssiere JL, Mignotte B, Kroemer G, Castedo M. (1997) Implication of mitochondria in apoptosis. Mol. Cell. Biochem. 174, 185-188 https://doi.org/10.1023/A:1006848205880
  17. Sakagami Y, Mizoguchi Y, Miyajima K, Yamamoto S, Takeda S, Aburada M, Morisawa S. (1985) Effects of the Chinese prescription 'inchinko-to' on intrahepatic cholestasis induced by the cholestatic factor. Nippon hokakibyo Gakkai Zasshi. 82, 2608-2612
  18. Shao F, Wang G, Xie H, Zhu X, Sun J, A Jiye. (2007) Pharmacokinetic study of triptolide, a constituent of immunosuppressive chinese herb medicine, in rats. Biol. Pharm. Bull. 30, 702-707 https://doi.org/10.1248/bpb.30.702
  19. Shoda J, Miura T, Utsunomiya H, Oda K, Yamamoto M, Kano M, Ikegami T, Tanaka N, Akita H, Ito K, Suzuki H, Sugiyama Y. (2004) Genipin enhances Mrp2 (Abcc2)-mediated bile formation and organic anion transport in rat liver. Hepatology 39, 167-178 https://doi.org/10.1002/hep.20003
  20. Singh SV, Zeng Y, Xiao D, Vogel VG, Nelson JB, Dhir R, Tripathi YB. (2005) Caspase-dependent apoptosis induction by guggulsterone, a constituent of ayurvedic medicinal plant commiphora mukul, in PC-3 human prostate cancer cells is mediated by Bax and Bak. Mol. Cancer Ther. 4, 1747-1754 https://doi.org/10.1158/1535-7163.MCT-05-0223
  21. Thornberry NA. (1998a) Caspases: key mediators of apoptosis. Chem. Biol. 5, 97-103 https://doi.org/10.1016/S1074-5521(98)90615-9
  22. Thornberry NA, Lazebnik Y. (1998b) Caspases: enemies within. Science. 281, 1312-1316 https://doi.org/10.1126/science.281.5381.1312
  23. Wasser S, Ho JM, Ang HK, Tan CE. (1998) Salvia miltiorrhiza reduces experimentally-induced hepatic fibrosis in rats. J. Hepatol. 29, 760-771 https://doi.org/10.1016/S0168-8278(98)80257-2
  24. Wyllie AH. (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284, 555-556 https://doi.org/10.1038/284555a0
  25. Yamamoto M, Ogawa K, Morita M, Fukuda K, Komatsu Y. (1996) The herbal medicine Inchin-ko-to inhibits liver cell apoptosis induced by ransforming growth factor beta 1. Hepatology. 23, 552-559 https://doi.org/10.1002/hep.510230322
  26. Yamashiki M, Mase A, Arai I, Huang XX, Nobori T, Nishimura A, Sakaguchi S, Inoue K. (2000) Effects of the Japanese herbal medicine 'Inchinko-to' (TJ-135) on concanavalin A-induced hepatitis in mice. Clin. Sci (Lond). 99, 421-431 https://doi.org/10.1042/CS20000031
  27. Zhu AX. (2006) Systemic therapy of advanced hepatocellular carcinoma: how hopeful should we be Oncologist. 11, 790-800

피인용 문헌

  1. Prescription frequency and patterns of Chinese herbal medicine for liver cancer patients in Taiwan: a cross-sectional analysis of the National Health Insurance Research Database vol.17, pp.1, 2017, https://doi.org/10.1186/s12906-017-1628-0