Comparative assessment of anticancer effects of natural bioactive compounds in breast cancer

Breast cancer is the most frequently observed cancer in women with a high mortality rate, and is the cause of 25.4% of newly diagnosed cancers in the world. Breast cancer has a heterogenous and complex character in cellular compositions and clinical results, and is classified into estrogen receptor positive (ER+/PR+/HER2-) and the more aggressive triple-negative (ER-/PR-/HER2-) molecular subgroups. Its highly aggressive nature necessitates the use of multiple, combined synthetic chemotherapeutic and radiotherapeutic regimens. Since these treatments are complicated by serious side effects, new targets/agents or supportive treatment options are needed. Scientists, therefore, investigate natural bioactive compounds without important side effects, but with antioxidant, anti-inflammatory and anticancer characteristics. Among these, thymoquinone (TQ) isolated from black cumin/seeds, caffeic acid phenethyl ester (CAPE) from honeybee propolis and fucoidan (FC) from the brown seaweed Fucus vesiculosus have become the center of scientific attention. However, a comparative assessment of the anticancer properties of these molecules has, thus far, not been made in a single study. Here, dose and time-dependent cytotoxic activities of TQ, CAPE and FC on MCF-7 (ER+/PR+/HER2-) and triple negative MDA-MB-231 (ER-/PR-/HER2-) breast cancer cell lines were compared. Cytotoxic activities were determined using both XTT cell viability assay and xCELLigence real time cell monitoring system. TQ showed a stronger cytotoxicity than CAPE and FC in both MCF-7 and MDA-MB-231 cell lines. Although CAPE displayed noticeable cytotoxicity on ER+ MCF-7 cells, it was ineffective or even proliferative in ER- MDA-MB-231 cells. FC displayed no negative effects on viability of either cell line. Combination of TQ and CAPE may have potential synergistic anti-proliferative effect on ER+ MCF-7 cells. In conclusion, TQ is the most promising phytotherapeutic agent and a candidate drug in the battle against breast cancer in comparison to CAPE, whereas FC may not be a promising candidate from a cytotoxic point of view. Keywords: Anticancer effects, breast cancer, caffeic acid phenethyl ester, fucoidan, thymoqinone