Author(s): Kuo, HM (Kuo, Hsiu-Maan); Tsai, HC (Tsai, Hung-Chieh); Lin, YL (Lin, Ya-Ling);
Yang, JS (Yang, Jai-Sing); Huang, AC (Huang, An-Cheng); Yang, MD (Yang, Mei-Due); Hsu, SC (Hsu, Shu-Chun); Chung, MC (Chung, Meng-Chin); Wood, WG (Wood, W. Gibson);
Chung, JG (Chung, Jing-Gung)
Title: Mitochondrial-dependent caspase activation pathway is involved in baicalein-induced apoptosis in human hepatoma J5 cells
Source: INTERNATIONAL JOURNAL OF ONCOLOGY, 35 (4): 717-724 OCT 2009 Language: English
Document Type: Article
Author Keywords: baicalein; apoptosis; mitochondrial; caspase activation; human hepatoma J5 cells
KeyWords Plus: ENDOPLASMIC-RETICULUM STRESS; PROSTATE-CANCER CELLS; CA SKI CELLS; SCUTELLARIA-BAICALENSIS; CYCLE ARREST; OXIDATIVE STRESS; CDC2 KINASE; FLAVONOIDS; INDUCTION; DEATH
Abstract: Baicalein has been reported to induce growth-inhibitory activity in vitro in human cancer cells; however, the molecular mechanism of action is not completely understood. A pharmacological dose (10-100 mu M) of baicalein exerted a cytotoxic effect on human hepatoma J5 cells resulting in G2/M arrest and apoptosis. In addition to cytotoxicity in J5 cells, several apoptotic events including mitochondrial cytochrome c release, activation of caspase-9 and -3 occurred. Baicalein induced AIF and Endo G release from mitochondria indicating that baicalein stimulates apoptosis through the caspase-independent pathway, while undergoing apoptosis, there was a remarkable accumulation of G2/M cells. Also, the ratio of Bax/Bcl-2 was increased leading to changes in mitochondria membrane potential (Delta Psi(m)) and release of cytochrome c, whereas the baicalein-induced apoptosis was partially abrogated by pretreatment with the pan-caspase inhibitor z-VAD-fmk, the accumulation of G2/M cells remained. These results demonstrate that the cytotoxicity of baicalein in J5 cells is attributable to apoptosis mainly involving G2/M-arrest in an ER-dependent manner, via a mitochondria- dependent caspase pathway and as well as contributions of AIF and Endo G pathways.
Addresses: [Kuo, Hsiu-Maan; Tsai, Hung-Chieh; Lin, Ya-Ling] China Med Univ, Dept
Parasitol, Taichung 404, Taiwan; [Yang, Jai-Sing] China Med Univ, Dept Pharmacol, Taichung 404, Taiwan; [Huang, An-Cheng] St Marys Med Nursing & Management Coll, Dept Nursing, Yilan Cty 216, Taiwan; [Yang, Mei-Due] China Med Univ Hosp, Dept Surg, Taichung 404, Taiwan; [Hsu, Shu-Chun] China Med Univ, Sch Nutr, Taichung 404, Taiwan; [Chung, Meng- Chin] Natl Tsing Hua Univ, Dept Life Sci, Hsinchu 300, Taiwan; [Chung, Meng-Chin] Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol, Coll Life Sci, Hsinchu 300, Taiwan; [Wood, W.
Gibson] Univ Minnesota, Dept Pharmacol, Sch Med & Geriatr Res, Educ & Clin Ctr,VA Med Ctr, Minneapolis, MN 55455 USA; [Chung, Jing-Gung] China Med Univ, Dept Biol Sci &
Biotechnol, Taichung 404, Taiwan; [Chung, Jing-Gung] Asia Univ, Dept Biotechnol, Taichung 413, Taiwan
Reprint Address: Chung, JG, China Med Univ, Dept Biol Sci & Technol, 91 Hsueh Shih Rd, Taichung 404, Taiwan.
E-mail Address: [email protected] Funding Acknowledgement:
Funding Agency Grant Number
China Medical University CMU95-110
NIH AG23524
AG18357
This work was supported by grants CMU95-110 from the China Medical University and NIH grants AG23524 and AG18357.
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Publisher: SPANDIDOS PUBL LTD
Publisher Address: POB 18179, ATHENS, 116 10, GREECE ISSN: 1019-6439
DOI: 10.3892/ijo_00000384
29-char Source Abbrev.: INT J ONCOL ISO Source Abbrev.: Int. J. Oncol.
Source Item Page Count: 8 Subject Category: Oncology ISI Document Delivery No.: 494AD
