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Year : 2022  |  Volume : 12  |  Issue : 9  |  Page : 400-410

Extract of Codiaeum luzonicum Merr. overcomes multidrug resistance in human colon cancer cells by modulating P-glycoprotein

Institute of Biology, University of the Philippines Diliman, Quezon City, Metro Manila, Philippines

Correspondence Address:
Regina Joyce E. Ferrer
Institute of Biology, University of the Philippines Diliman, Quezon City, Metro Manila
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2221-1691.354431

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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 EC50 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 EC50 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.

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