Inhibitory effects of asiatic acid and CPT-11 on growth of HT-29 cells.
Asiatic acid is a pentacyclic triterpene contained in medicinal plants. The cytotoxic effect of this compound and its augmentative effect on the anticancer drug irinotecan hydrochloride (CPT-11) were investigated in the human colon adenocarcinoma cell line HT-29. Asiatic acid dose-dependently showed cytotoxicity in HT-29 cells. DNA fragmentation, annexin-positive apoptotic cells, and caspase-3 activation were observed in a dose-dependent manner. A caspase-3 inhibitor suppressed the DNA ladder formation in a concentration-dependent manner. Bcl-2 and Bcl-XL proteins were decreased by asiatic acid treatment. These results indicate that asiatic acid induced apoptosis in HT-29 cells via caspase-3 activation. Cytotoxic effects of combined treatment with CPT-11 and asiatic acid on HT-29 cells were further examined. Simultaneous treatment or sequential exposure first to asiatic acid and then to CPT-11 showed an additive effect. Synergism was observed when cells were first exposed to CPT-11 and then to asiatic acid. These results suggest that asiatic acid can be used as an agent for increasing sensitivity of colon cancer cells to treatment with CPT-11 or as an agent for reducing adverse effects of CPT-11.
Bunpo
Piyawan
P
Department of Molecular Bacteriology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Kataoka
Keiko
K
Arimochi
Hideki
H
Nakayama
Haruyuki
H
Kuwahara
Tomomi
T
Vinitketkumnuen
Usanee
U
Ohnishi
Yoshinari
Y
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000077146:Irinotecan; C017032:asiatic acid; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002166:Camptothecin