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Effects of Momordica charantia Extract on the Expression of MDR 1 Gene in Human Lung Cancer Cells

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Objectives: Multi-drug resistance (MDR) is a major hurdle in treatment of cancer, contributing to the failure of chemotherapy. Drug resistance is found to be linked to the overexpression of ATP-binding cassette (ABC) drug transporter proteins that include P-glycoprotein (P-gp), causing a reduction in drug accretion inside the cancer cells. In the present study, the effect of the extracts from the fruit peel and pulp of Momordica charantia (MCFPE) fruit in modulating the function of P-gp in human small-cell lung cancer (SCLC) cell lines was assessed.

Methods: The effects of MCFPE were tested on drug-sensitive (H69) and multi-drug resistant (H69/LX4) human SCLC cells. The cell survival percentage was assessed by MTT cytotoxicity assay. The percentage of drug accumulation and drug efflux were assessed by using [3H]-paclitaxel. The expression of MDR1 gene was analysed by reverse transcription polymerase chain reaction (RT-PCR), and P-gp by western blot analysis.

Results: The extract was able to induce death of cancer cells as measured by cell survival percentage as well as improve drug accumulation, as evidenced by intracellular paclitaxel retention. Prior exposure of cells to MCFPE reversed resistance to paclitaxel. Treatment with MCFPE was found to have a significant impact on MDR 1 gene expression in H69/LX4 cell line by decreasing its expression. The extract had no influence on expression of MDR 1 gene in the drug-sensitive SCLC cell lines. Western blot analysis of P-gp protein in H69 and H69/LX4 cells revealed that the treatment with the extract modulates the expression of MDR 1 in H69/LX4 and had negligible effect on H69 cells. 

Conclusion: The results indicate that MCFPE was able to effectively reverse multi-drug resistance and improve cancer chemotherapy. 

June 30, 2014
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