Cytotoxicity and Antioxidant Potential of Vanillin from Coffee Peel Extract and Sorafenib in human MDAMB-231 Breast Cancer cells: A Potential Therapeutic strategy

Abstract

Breast cancer (BC) is the most prevalent malignancy among women in Egypt, accounting for 34.9% of all female cancer cases. Given the frequent limitations of conventional treatments, the need for alternative therapeutic strategies remains critical. Vanillin, naturally occurring phenolic compound, has demonstrated multiple bioactive properties, including anti-inflammatory, anticancer, and antioxidant effects. Objective:This study aimed to assess the cytotoxic effects of vanillin derived from Coffee Peel Extract and sorafenib (SOR), an anti-hepatocellular carcinoma drug, using the triple-negative breast cancer(TNBC) MDA-MB-321 cell line. Additionally, we investigated their individual and combined impact on lipid peroxidation and antioxidant enzyme activity.Methods:MDA-MB-321 cells were treated with varying concentrations of vanillin (50–200 µM) and SOR(6.25–100 µM)for 48 hours, after which cell viability was assessed using the MTT assay.The activity of superoxide dismutase (SOD) and catalase(CAT)—key antioxidant enzymes—was quantified using colorimetric assays, while malondialdehyde (MDA) levels, a biomarker of lipid peroxidation, were also measured. Results:Both SOR and vanillin significantly (P < 0.001) reduced MDA-MB-321 cell viability.However, SOR exhibited greater cytotoxicity (IC90 = 144.8 ± 5.1µg/ml) compared to vanillin(IC90 = 255.4 ± 6.5 µg/ml).In comparison to untreated and DMSO-treated control cells, SOR treatment alone resulted in the highest SOD and CAT activity,whereas the combination of SOR and vanillin led to the lowest MDA levels, indicating reduced oxidative stress. Conclusion:These findings suggest that SOR and vanillin exert anticancer effects inTNBC cells by modulating lipid peroxidation and antioxidant defense mechanisms. This study provides insight into their potential mechanism of action, supporting further exploration of vanillin-based combination therapies for breast cancer treatment.