Synergistic Cytotoxic and Cell Cycle-Regulating Effects of Garcinia cowa Leaf Extract and Trastuzumab in HER2-Positive Breast Cancer Cells
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Abstract
HER2-positive breast cancer is highly aggressive, with poor prognosis and resistance to standard therapies. Although trastuzumab is the standard therapy, its effectiveness is often limited by resistance and cardiotoxic side effects. Therefore, adjuvant therapy strategies are needed to improve the response to trastuzumab. This study evaluated the synergistic effect of Garcinia cowa leaf extract and trastuzumab on MCF-7/HER2 breast cancer cells. Cells were treated with various concentrations of G. cowa leaf extract and trastuzumab, either singly or in combination. Cytotoxicity was assessed using a tetrazolium reduction assay, while synergism was evaluated with the Combination Index (CI). Flow cytometry was employed for cell cycle analysis, apoptosis detection, and the assessment of protein expression (p53, Cyclin D1, and Cyclin E). The results indicated that G. cowa extract had an IC50 of 119.21 µg/mL, whereas trastuzumab had an IC50 of 954.52 µg/mL. The combination of 25 µg/mL extract and 125 µg/mL trastuzumab produced an optimal synergistic effect (Fa = 0.897, CI = 0.266), inducing G2/M arrest with the cell population increasing to 54.6%, reducing cell viability to 73.4%, and elevating the apoptotic fraction by 17.2%. Protein expression analysis revealed an increase in p53 and decreases in Cyclin D1 and Cyclin E, contributing to the inhibition of cell proliferation. Overall, G. cowa leaf extract enhances the effectiveness of trastuzumab through cell cycle modulation and apoptosis induction, suggesting its potential as an adjuvant therapy for HER2-positive breast cancer. Further studies using in vivo models and clinical validation are needed to confirm these findings.
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