Anticancer activity of sodium caffeate and its mechanism.
OBJECTIVE
To study the anticancer activity of sodium caffeate (SC).


METHODS
A nucleoside transport assay was used to analyze the inhibitory effects of SC on nucleoside rescue. The MTT assay was used to measure cell proliferation. Flow cytometry was used to measure the apoptosis of BEC-7402 induced by SC and the cell cycle distribution change. Western blotting analysis was employed to investigate Bcl-2, caspase and Bax expression. Intracellular Ca2+ and mitochondrial membrane potential were determined by flow cytometry. In vivo anti-tumor activity was measured using a tumor transplantation model in mice.


RESULTS
SC inhibited the nucleoside transport of BEL-7402 cells with an IC(50) of 1.02 microg/mL. SC inhibited tumor cell proliferation with an IC50 between 100 microg/mL and 200 microg/mL. SC induced BEL-7402 cell apoptosis in a time- and dose-dependent manner, which was induced by arresting cells in S phase. The in vivo study showed that tumor growth was inhibited in a dose-dependent manner. Activated caspase-3 and Bax expression were up-regulated after treatment with SC, while Bcl-2 expression was down-regulated. Intracellular Ca2+ was increased while mitochondrial membrane potential was decreased by SC.


CONCLUSIONS
SC is a new anticancer agent with promising potential.
Xu
Feng
F
Department of Pharmacology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Zhang
Shen-hua
SH
Shao
Rong-guang
RG
Zhen
Yong-su
YS
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D002109:Caffeic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D002118:Calcium; C040048:caffeic acid