(-)-Anonaine induces apoptosis through Bax- and caspase-dependent pathways in human cervical cancer (HeLa) cells.
(-)-Anonaine has been shown to have some anticancer activities, but the mechanisms of (-)-anonaine inducing cell death of human cancer cells is not fully understood. We investigated the mechanisms of apoptosis induced by (-)-anonaine in human HeLa cancer cells. Treatment with (-)-anonaine induces dose-dependent DNA damage that is correlated with increased intracellular nitric oxide, reactive oxygen species, glutathione depletion, disruptive mitochondrial transmembrane potential, activation of caspase 3, 7, 8, and 9, and poly ADP ribose polymerase cleavage. Our data indicate that (-)-anonaine up-regulated the expression of Bax and p53 proteins in HeLa cancer cells. The apoptosis and expression of Bax induced by (-)-anonaine could be inhibited when the HeLa cells were pretreated with Boc-Asp(OMe)-fmk, which is a broad caspases inhibitor. There was no obvious DNA damage in the (-)-anonaine-treated Madin-Darby canine kidney and Vero cell lines. Both Madin-Darby canine kidney and Vero cell lines are kidney epithelial cellular morphology. These results suggest that (-)-anonaine might be considered a potent compound for chemotherapy against cervical cancer or a health food supplement for cancer chemoprevention.
School of Medicine and Health Sciences, Fooyin University, Kaohsiung Hsien 831, Taiwan.
Chung-Yi
CY
Chen
Tsan-Zon
TZ
Liu
Wei-Chang
WC
Tseng
Fung-Jou
FJ
Lu
Ray-Ping
RP
Hung
Chi-Hung
CH
Chen
Ching-Hsein
CH
Chen
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001060:Aporphines / Q000494:pharmacology*; D020169:Caspases / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004149:Dioxoles / Q000494:pharmacology*; D005434:Flow Cytometry; D005978:Glutathione / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D001060:Aporphines; D004149:Dioxoles; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; C098138:anonaine; D009569:Nitric Oxide; D020169:Caspases; C022616:thiazolyl blue; D005978:Glutathione