Imaobong Etti

By Imaobong Etti, Rasedee Abdullah and Arifah Kadir

Breast cancer is among the principal cause of cancer fatalities in women. Notwithstanding the use of chemotherapy and advances in drug delivery techniques, cancer-related morbidity and mortality are still increasing with the increase in resistance to known therapeutics. This dilemma has drastically reduced the rate of survival from this deadly disease, creating a dire need for new drugs, especially from natural sources that would exhibit similar or better anticancer properties while imparting minimal adverse side effects. Among the bewildering hallmark capabilities of cancer is the evasion of apoptosis while in its course to immortality. Thus, induction of apoptosis in cancerous cells is an important breakthrough that cannot be ignored. There are, however, two major pathways of apoptosis in mammals, viz., the death receptor–mediated pathway (extrinsic pathway) and the mitochondrial-mediated pathway (intrinsic pathway). Artonin E, a prenylated flavonoid isolated from the stem bark of Artocarpus elasticus, was seen to induce apoptosis in MCF-7 breast cancer cells, hence halting the breast cancer cells in their journey to immortality.

Part of the book: Current Understanding of Apoptosis

By Imaobong Etti, Chukwuemeka Nwafor and Grace Essien

The sex hormone estrogen plays critical roles in reproductive and sexual development. It regulates the expression and activity of key signaling molecules critical in various cellular signaling pathways. These signals are mediated by its binding to estrogen receptors alpha (ERα) and beta (ERβ). ERα has been shown to greatly participate in extranuclear signaling, inducing tumorogenesis and breast cancer metastasis. Small molecules from plants are reported with better selectivity toward tumorigenic cells with negligible toxicity when compared to their synthetic counterpart. The molecules used in this study were first probed for their drug-likeness and their pharmacokinetic profile was elucidated before docking them to the ligand binding domain of the human ERα followed by a post docking prime analysis. All tested molecules had good drug-like and pharmacokinetic properties when compared to about 95% of orally available drugs as predicted by qikprop. The docking results revealed a strong binding interaction with ERα, influenced mostly by the vicinal diol groups of the studied molecules. These resulted in a conformational change, inducing receptor dimerization and altering the interactions of the sex hormone with other proteins. The studied ligands are promising in strongly inhibiting the binding of estrogen to ERα, thus limiting its extranuclear signaling.

Part of the book: Reproductive Hormones