Abstract
Breast cancer remains one of the primary causes of death among women globally. Doxorubicin (DOX) is a widely used chemotherapeutic drug in breast cancer therapy. However, it is limited by the development of chemoresistance and its cardiotoxic effects. Curcumin (CUR), a natural anticancer agent is promising in promoting apoptosis in cancer cells while sparing the healthy cells. Therefore, this project aims to study the combined anticancer effects of DOX and CUR in the human breast cancer MDA-MB-231 and MCF-7 cells. The half inhibitory concentration (IC50) of the combined DOX and CUR was determined prior to subjecting the cells treated with IC50 of the drugs to cell viability (MTT and trypan blue), wound healing, hematoxylin and eosin (H&E) staining and reverse transcription-polymerase chain reaction (RT-PCR) targeting CDH1 by using β-actin as the housekeeping gene. The IC50 determined was 0.8 µM and 20 µM for DOX and CUR, respectively. The cell viability of MDA-MB-231 and MCF-7 decreased in time-dependent manner; however, MCF-7 exhibited a sudden increase at 48 hours, suggesting potential development of resistance. Trypan blue exclusion test showed that both cells displayed decreased cell viability, with MDA-MB-231 displayed greater decrease in cell viability. The cell migration of MDA-MB-231 was lower than the untreated cells at 72 hours while for MCF-7, the cell migration was reduced at 24 and 48 hours. H&E staining revealed various apoptotic morphological changes in the treated cells. RT-PCR results showed that CDH1 expression was highest for MDA-MB-231 at 24 hours after the combined treatment, indicating reduced epithelial–mesenchymal transition (EMT), thus inhibited metastasis. In conclusion, the combined DOX and CUR treatment shows promising potential in enhancing the anticancer effects by reducing cell viability, inhibiting the cell migration pathway as well as inducing apoptosis execution, overall mitigating the limitations of the existing breast cancer therapies.
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