The role of Ca+2 on rhein-induced apoptosis in human cervical cancer Ca Ski cells.

Abstract

Apoptosis induced by rhein, an active component of senna, has been reported in various human cancer cells, however, its molecular mechanisms are not precisely known. In this study, the mechanisms of apoptosis by which rhein acts on human cervical cancer Ca Ski cells were examined. Flow cytometric analysis demonstrated that rhein induced the abrogation of mitochondrial membrane potential (MMP) and cleavage of Bid protein. Rhein also induced an increase in the levels of Fas, p53, p21 and Bar, but a decrease in the level of Bcl-2. The activities of both caspase-8 and -9 were enhanced by rhein, promoting caspase-3 activation, leading to DNA fragmentation, thus, indicating that rhein-induced apoptosis is caspase-dependent. In addition, rhein induced an increase in the level of cytoplasmic Ca2+, which was inhibited by BAPTA (a calcium chelator). BAPTA attenuated the MMP abrogation and significantly dinimished the occurrence of rhein-induced apoptosis in Ca Ski cells. In conclusion, our data demonstrate that rhein-induced apoptosis occurs via a caspase-dependent and mitochondria-dependent pathway which is closely related to the level of cytoplasmic Ca2+ in Ca Ski cells.

• Authors: Siu-Wan Ip, Yueh-Shan Weng, Shuw-Yuan Lin, Mei-Dueyang, Nou-Ying Tang, Chin-Cheng Su, Jing-Gung Chung
• Journal: Anticancer research (Anticancer Res) 2007 Jan-Feb Vol. 27 Issue 1A Pg. 379-89 ISSN: 0250-7005 [Print] Greece
• PMID: 17352257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthraquinones
• BAX protein, human
• BH3 Interacting Domain Death Agonist Protein
• BID protein, human
• Fluorescent Dyes
• Indoles
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• TP53 protein, human
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• fas Receptor
• DAPI
• Egtazic Acid
• Cytochromes c
• Caspases
• 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
• Calcium
• rhein

Topics

• Anthraquinones (pharmacology)
• Apoptosis (drug effects, physiology)
• BH3 Interacting Domain Death Agonist Protein (metabolism)
• Blotting, Western
• Calcium (metabolism)
• Caspases (metabolism)
• Cell Line, Tumor
• Cytochromes c (metabolism)
• Cytoplasm (drug effects, metabolism)
• DNA Fragmentation (drug effects)
• Egtazic Acid (analogs & derivatives, pharmacology)
• Female
• Fluorescent Dyes
• Humans
• Indoles
• Membrane Potential, Mitochondrial (drug effects, physiology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Tumor Suppressor Protein p53 (metabolism)
• Uterine Cervical Neoplasms (drug therapy, metabolism, pathology)
• bcl-2-Associated X Protein (metabolism)
• fas Receptor (metabolism)