Résumé
Objective: To investigate anti-multidrug resistance (MDR) activity and safety of the bioactive fraction (CL11) from Codiaeum luzonicum crude leaf extract. Methods: Cytotoxic activity of CL11 against MDR and non- resistant colon cancer cells was assessed using MTT assay. Mode of cell death was investigated by annexin V-propidium iodide staining, TUNEL, and JC-1 assays. To examine mechanism of action, the effect on the expression and function of the MDR-implicated protein P-glycoprotein was tested using Western blotting and calcein assay, respectively. Results: CL11 had an EC 50 of 0.18, 1.03 and 38.52 μg/mL against HCT-15, HCT-15/Dox and HCT116, respectively. Cytotoxicity was mediated by inhibition of P-glycoprotein function and expression. The mode of cell death involved mitochondrial membrane depolarization and was mostly non-apoptotic at EC 50 concentrations against HCT-15 and HCT-15/Dox. Conclusions: Fraction CL11 of Codiaeum luzonicum induces non- apoptotic cell death in MDR cancer cells by overcoming MDR through inhibition of P-glycoprotein expression and function.
Résumé
Objective: To evaluate the cytotoxic activities of Premna odorata (P. odorata) leaves and bark, Artocarpus camansi (A. camansi) and Gliricidia sepium against selected human cancer cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Methods: The crude extracts of P. odorata, A. camansi and Gliricidia sepium were subjected to liquid-liquid partitioning by using hexane and ethyl acetate to separate compounds based on their polarity. The fractions were tested for their cytotoxic activity against human colon cancer cell line (HCT116), breast cancer cell line (MCF-7), lung adenocarcinoma cell line (A549) and Chinese hamster ovary cell line (AA8) by using MTT assay. Results: Based on the standard values of toxicity set by the study of Suffness and Pezzuto, P. odorata leaves and P. odorata bark hexane fractions and A. camansi leaves were all considered highly cytotoxic against the selected human cancer cell lines. P. odorata bark hexane extract exhibited the highest selectivity index for HCT116, MCF-7 and A549 cancer cell lines. Conclusions: The results obtained indicated that P. odorata leaves and bark and A. camansi leaves have excellent cytotoxic activity and warrant further studies to isolate novel compounds for chemotherapeutic use.