[Rhein induces apoptosis in cancer cells and shows synergy with mitomycin].
OBJECTIVE
To study the apoptosis-inducing and growth-inhibitory effect of rhein, an herb-derived compound, and its combination with mitomycin C (MMC) on cultured tumor cells.


METHODS
MTT assays were used to determine the inhibition of proliferation by drugs in several tumor cell lines. Nucleoside transport and DNA synthesis inhibition were determined by [3H] thymidine transport and incorporation assays. Flow cytometry, electrophoresis on agarose gels and morphological assessment were applied to analyze the apoptotic changes.


RESULTS
The IC50 values of nucleoside transport was 19.1 micrograms.mL-1 and that of the DNA synthesis inhibited by rhein was 27.4 micrograms.mL-1. In MTT assay the IC50 values of rhein for KB, hepatoma BEL-7402 and mammary carcinoma MCF-7 cells were 11.5 micrograms.mL-1, 14.0 micrograms.mL-1 and 18.4 micrograms.mL-1 respectively. Synergistic effect of rhein and MMC was found in all the three cell lines. As found, rhein induced apoptosis in KB cells, and the increase of apoptotic cells reached 71.0% at 96 h. The combination of rhein and MMC enhanced the induction of apoptosis significantly.


CONCLUSIONS
These results suggest that rhein, as a biochemical modulator, might be potentially useful in cancer chemotherapy.
Huang
Y H
YH
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Pekin Union Medical College, Beijing 100050, China.
Zhen
Y S
YS
D000880:Anthraquinones / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004357:Drug Synergism; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D016685:Mitomycin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000880:Anthraquinones; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D016685:Mitomycin; C020491:rhein