Chrysophanol-induced necrotic-like cell death through an impaired mitochondrial ATP synthesis in Hep3B human liver cancer cells.
Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanol-induced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca(2+) production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanol-induced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.
Department of Chinese Medicine, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan.
Chien-Hang
CH
Ni
Po-Yuan
PY
Chen
Hsu-Feng
HF
Lu
Jai-Sing
JS
Yang
Hui-Ying
HY
Huang
Shin-Hwar
SH
Wu
Siu-Wan
SW
Ip
Chin-Tung
CT
Wu
Su-Yin
SY
Chiang
Jaung-Geng
JG
Lin
W Gibson
WG
Wood
Jing-Gung
JG
Chung
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000880:Anthraquinones / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis
D000880:Anthraquinones; D000255:Adenosine Triphosphate; C027113:chrysophanic acid