Abstract
Triple negative breast cancer is one of the most aggressive breast cancer type with abilities of early metastasis and chemoresistance. The tropical plant Citrus hystrix DC. has been reported to promote many biological activities including anticancer. However, the effect of C. hystrix against triple negative breast cancer has not yet been identified. This study aimed to evaluate the anticancer properties of C. hystrix leaf extract and its bioactive constituents citronellol and citronellal against the triple negative breast cancer MDA-MB-231 cell line. C. hystrix leaves were powdered and sequentially macerated. The in vitro anticancer effects of C. hystrix leaf extracts, and its bioactive constituents (citronellol and citronellal) were evaluated against MDA-MB-231 cell line using cytotoxic MTT assay, cell proliferation, wound scratch migration, colony formation, cell cycle, apoptosis assay, Hoechst staining, RT-qPCR, and Western blot analysis. Results showed that crude hexane extract, citronellol, and citronellal significantly reduced cell proliferation, colony formation, and cell migration by inducing cell cycle arrest, while also inducing apoptosis in MDA-MB-231 cells through inhibition of anti-apoptotic Bcl-2 expression, leading to activation of the caspase-3-dependent pathway. This study is the first report to demonstrate the effect of C. hystrix, citronellol, and citronellal against triple negative breast cancer MDA-MB-231 cells.
Highlights
Triple negative breast cancer (TNBC) is a sub-type of breast cancer
Several new anticancer plant-derived molecules have been put through clinical trials [6] and some such as cabazitaxel and homoharringtonine have been approved by the FDA for use in treatment resistance [7,8]
Maceration C. hystrix leaf powder with hexane solvent resulted in a sticky dark green extract with yield of 1.1% (w/w dried powder)
Summary
Triple negative breast cancer (TNBC) is a sub-type of breast cancer. TNBC accounts for 15–20% of invasive breast cancers in women [3] and presents a higher frequency of recurrence and lower overall survival rate compared to non-TNBC patients [4]. It is one of the most aggressive types of breast cancer due to its early metastasis and resistance to chemotherapies such as anthracyclines, taxanes, and many others [5]. Several new anticancer plant-derived molecules have been put through clinical trials [6] and some such as cabazitaxel and homoharringtonine have been approved by the FDA for use in treatment resistance [7,8]. Plant materials are becoming increasingly recognized as a substantial source of anticancer agents and urgently require assessment for future development
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