Green Tea Leaves and Rosemary Extracts Selectively Induce Cell Death in Triple-Negative Breast Cancer Cells and Cancer Stem Cells and Enhance the Efficacy of Common Chemotherapeutics

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Abstract
While incredible medical advancements in chemotherapeutics development for cancer treatment have been made, the majority of these are not selective in their mechanism of action, leading to adverse effects. Given the systemic toxicity associated with these therapies, they are not well suited for long-term use. Natural health products, or NHPs, may provide a way to selectively target the oxidative and metabolic vulnerabilities in cancer cells. White tea (Camelia sinensis) and rosemary (Salvia rosmarinus) are two natural extracts that have been studied extensively for their medicinal properties. However, their anticancer activity and mechanism of action are yet to be fully elucidated. We have examined the extracts cancer cell-killing ability as well as their interactions with common chemotherapeutics in MDA-MB-231cells, a triple-negative breast cancer cell line, in vitro. Cell death measurement, morphological and biochemical characterization of apoptotic cell death, mechanisms of action (mitochondrial depolarization and oxidative stress), and immunofluorescence assays to estimate the percentage of cancer stem cells (CSCs) were performed following treatment with Synthite tea extract (STE) and rosemary extract (RE), provided by Synthite Industries Limited alone and in combination with cisplatin and paclitaxel. The key findings in this study are that STE and RE alone demonstrated very efficient anticancer activity against TNBC, and more importantly, the administration of the extracts in conjunction with cisplatin and paclitaxel sensitizes cancer cells to achieve enhanced cell death. In addition, CSCs were found to be sensitive to treatment with STE alone and in combination with RE and exhibited greater sensitivity to combination therapies compared to chemotherapeutic alone. The significance of these observations is that STE and RE, well-tolerated NHPs, have the potential to enhance the efficacy of current chemotherapeutics when combined, as well as prevent relapse for TNBC.
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