Deoxycholic acid-formulated curcumin enhances caspase 3/7-dependent apoptotic induction in cholangiocarcinoma cell lines

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Pattaravadee Srikoon
Putthiporn Khongkaew
Watcharapong Chamsawang
Suchada Phimsen
Kulthida Vaeteewoottacharn

Abstract

Cholangiocarcinoma (CCA), a bile duct cancer, is a significant health problem in Thailand. The major obstacle in CCA treatment is having no effective therapeutic regimen, particularly for late-stage disease. The potent effects of curcumin on CCA have previously been documented, but the application of curcumin has been limited by its solubility and stability. Therefore, this study used liposomes, a well-known drug delivery vehicle, to transport curcumin for enhancing its efficacy. Deoxycholic acid (DCA), a secondary bile acid that has its receptors located on bile duct cells, was selected for the preparation of liposome-mediated curcumin delivery by the thin-film hydration method. The efficacy of DCA-formulated curcumin-containing liposomes (dLip/Cur) on two CCA cells, KKU-213A and KKU-213B, were compared with curcumin-containing liposomes (Lip/Cur) and curcumin alone by determinations of cell proliferation and apoptosis. The results demonstrate that IC50s of dLip/Cur in CCA cell lines were lower than those of other regimens. The growth inhibitory effect of dLip/Cur was partly due to the promotion of caspase-dependent apoptosis. Altogether, the usefulness of DCA-formulated liposomes as an anti-cancer delivery system for CCA treatment is suggested herein. It might be useful as a novel vehicle for CCA treatment in the future.

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