Ching Hui Chen1, Linda A deGraffenried. 1. Department of Nutritional Sciences, School of Human Ecology, the University of Texas at Austin, TX 78712, USA.
Abstract
BACKGROUND: Many traditional Chinese medicines target the treatment of inflammation which is emerging to be a critical component to cancer development and progression. The key aromatic compound in star anise anethole has demonstrated both anti and pro-cancerous effects depending on the estrogen receptor statuses in individual cell lines. In this study, we investigated the effect of anethole on the physiological responses and specific apoptotic pathways in human breast cancer MCF-7 and MDA-MB-231 cells that are well-characterized to represent estrogen receptor (ER) positivity and its counterpart in breast cancer respectively. How anethole affects the activity and expression of apoptotic caspases, the function of transcriptional factor NF-kB and the relative influence ER exerts on these events are areas of significant research relevance and results may impact the pharmaceutical development of anethole and its use as dietary supplementation. METHODOLOGY/PRINCIPAL FINDINGS: Initial analyses of physiological responses using MTT and colony formation assays had demonstrated a preferentially suppression of cell survival to cell proliferation in both ER+ and ER- cells when cells were exposed to anethole. Western blot analysis has demonstrated induction of caspase 9 and PARP1/2 cleavage in parallel with elevated expression of c-FLIP (s) and p53. The transcriptional activity of NF-kB, an upstream activator of p53 is suppressed in both cell lines when treated with anethole. CONCLUSIONS: In conclusion, anethole in an ER independent manner suppresses cell survival and induces apoptotic events in MCF-7 and MDA-MB-231 at an optimal concentration of 1 × 10(-3)M. In search of alternative compounds for therapeutic development, this study has demonstrated that anethole may be viable as an anti-cancer agent through the modulation of apoptosis, cell survival and proliferation in breast cancer cells.
BACKGROUND: Many traditional Chinese medicines target the treatment of inflammation which is emerging to be a critical component to cancer development and progression. The key aromatic compound in star aniseanethole has demonstrated both anti and pro-cancerous effects depending on the estrogen receptor statuses in individual cell lines. In this study, we investigated the effect of anethole on the physiological responses and specific apoptotic pathways in humanbreast cancer MCF-7 and MDA-MB-231 cells that are well-characterized to represent estrogen receptor (ER) positivity and its counterpart in breast cancer respectively. How anethole affects the activity and expression of apoptotic caspases, the function of transcriptional factor NF-kB and the relative influence ER exerts on these events are areas of significant research relevance and results may impact the pharmaceutical development of anethole and its use as dietary supplementation. METHODOLOGY/PRINCIPAL FINDINGS: Initial analyses of physiological responses using MTT and colony formation assays had demonstrated a preferentially suppression of cell survival to cell proliferation in both ER+ and ER- cells when cells were exposed to anethole. Western blot analysis has demonstrated induction of caspase 9 and PARP1/2 cleavage in parallel with elevated expression of c-FLIP (s) and p53. The transcriptional activity of NF-kB, an upstream activator of p53 is suppressed in both cell lines when treated with anethole. CONCLUSIONS: In conclusion, anethole in an ER independent manner suppresses cell survival and induces apoptotic events in MCF-7 and MDA-MB-231 at an optimal concentration of 1 × 10(-3)M. In search of alternative compounds for therapeutic development, this study has demonstrated that anethole may be viable as an anti-cancer agent through the modulation of apoptosis, cell survival and proliferation in breast cancer cells.
Authors: Dina M El-Kersh; Nada M Mostafa; Shaimaa Fayez; Tarfah Al-Warhi; Mohammed A S Abourehab; Wagdy M Eldehna; Mohamed A Salem Journal: J Enzyme Inhib Med Chem Date: 2022-12 Impact factor: 5.756