Abstract
Plants are an invaluable source of potential new anti-cancer drugs. Here, we investigated the cytotoxic activity of the acetonic extract of Buxus sempervirens on five breast cancer cell lines, MCF7, MCF10CA1a and T47D, three aggressive triple positive breast cancer cell lines, and BT-20 and MDA-MB-435, which are triple negative breast cancer cell lines. As a control, MCF10A, a spontaneously immortalized but non-tumoral cell line has been used. The acetonic extract of Buxus sempervirens showed cytotoxic activity towards all the five studied breast cancer cell lines with an IC50 ranging from 7.74 µg/ml to 12.5 µg/ml. Most importantly, the plant extract was less toxic towards MCF10A with an IC50 of 19.24 µg/ml. Fluorescence-activated cell sorting (FACS) analysis showed that the plant extract induced cell death and cell cycle arrest in G0/G1 phase in MCF7, T47D, MCF10CA1a and BT-20 cell lines, concomitant to cyclin D1 downregulation. Application of MCF7 and MCF10CA1a respective IC50 did not show such effects on the control cell line MCF10A. Propidium iodide/Annexin V double staining revealed a pre-apoptotic cell population with extract-treated MCF10CA1a, T47D and BT-20 cells. Transmission electron microscopy analyses indicated the occurrence of autophagy in MCF7 and MCF10CA1a cell lines. Immunofluorescence and Western blot assays confirmed the processing of microtubule-associated protein LC3 in the treated cancer cells. Moreover, we have demonstrated the upregulation of Beclin-1 in these cell lines and downregulation of Survivin and p21. Also, Caspase-3 detection in treated BT-20 and T47D confirmed the occurrence of apoptosis in these cells. Our findings indicate that Buxus sempervirens extract exhibit promising anti-cancer activity by triggering both autophagic cell death and apoptosis, suggesting that this plant may contain potential anti-cancer agents for single or combinatory cancer therapy against breast cancer.
Highlights
Breast cancer, a major worldwide health issue, is considered as the most common malignancy and the most common cause of cancer-related death in Western countries [1]
In order to evaluate the cytotoxicity of the acetonic extract of Buxus, an MTT assay was monitored on five breast cancer cell lines
In order to give a better understanding of the mechanisms of cytotoxicity in cancer cells, we decided to carry on experiments on aggressive triple positive cancer cells: MCF7, MCF10CA1a, T47D and the triple negative breast cancer cell line BT-20
Summary
A major worldwide health issue, is considered as the most common malignancy and the most common cause of cancer-related death in Western countries [1]. Standard cancer therapy generally combines surgery, multi-therapeutic agents and ionizing radiation [2]. These anticancer agents induce cell cycle arrest and/or cell death by apoptotic or non-apoptotic mechanisms including necrosis, senescence, autophagy and mitotic catastrophe [3,4]. Major issues concerning conventional anticancer chemotherapy are the occurrence of side effects induced by the non-specific targeting of both normal and cancer cells [5,6], and the emergence of drug-resistant cancer cells [7]. Natural products will continue to play major role as active substances, model molecules for the discovery and validation of drug targets [13,14]. Camptothecin from Camptotheca acuminata, Decne and podophyllotoxin from Podophyllum peltuturn L. [18,19]
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