Browsing by Author "Ekpo, E. O."
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Item Aqueous leaf extract of Sutherlandia frutescens attenuates ROS-induced apoptosis and loss of mitochondrial membrane potential in MPP+-treated SH-SY5Y cells(University of Benin, 2020) Ekpo, E. O.; Enogieru, Adaze Bijou; Omoruyi, Sylvester IfeanyiTo investigate the neuroprotective activity of the aqueous extract of Sutherlandia frutescens (SF) against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in SH-SY5Y neuroblastoma cells. Methods: SH-SY5Y neuroblastoma cells were divided into different treatment groups: untreated cells, cells treated with MPP+ alone (2 mM), cells pretreated with SF (20 μg) prior to MPP+ (2 mM) treatment and cells treated with SF (20 μg) alone. Twenty-four hours after treatment with MPP+, cell viability was assessed by MTT assay, and changes in cell morphology, intracellular reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) as well as caspases 3/7 and 9 activities were determined. Results: Treatment of SH-SY5Y cells with MPP+ alone significantly altered cellular morphology, increased ROS production (p = 0.005), induced a significant loss of MMP (p = 0.0011) and caused significant apoptotic cell death, via the activation of caspases 3/7 and 9 (p ≤ 0.0359). These effects were however significantly (p ≤ 0.0359) attenuated in cells pre-treated with the aqueous leaf extract of SF, indicating the possible neuroprotective activity of the SF extract.Item An insight into the mechanism of holamine- and funtumine-induced cell death in cancer cells(MDPI, 2020) Badmus, Jelili A.; Ekpo, E. O.; Sharma, Jyoti R.Holamine and funtumine, steroidal alkaloids with strong and diverse pharmacological activities are commonly found in the Apocynaceae family of Holarrhena. The selective anti-proliferative and cell cycle arrest effects of holamine and funtumine on cancer cells have been previously reported. The present study evaluated the anti-proliferative mechanism of action of these two steroidal alkaloids on cancer cell lines (HT-29, MCF-7 and HeLa) by exploring the mitochondrial depolarization effects, reactive oxygen species (ROS) induction, apoptosis, F-actin perturbation, and inhibition of topoisomerase-I. The apoptosis-inducing effects of the compounds were studied by flow cytometry using the APOPercentageTM dye and Caspase-3/7 Glo assay kit. The two compounds showed a significantly greater cytotoxicity in cancer cells compared to non-cancer (normal) fibroblasts. The observed antiproliferative effects of the two alkaloids presumably are facilitated through the stimulation of apoptosis. The apoptotic effect was elicited through the modulation of mitochondrial function, elevated ROS production, and caspase-3/7 activation. Both compounds also induced F-actin disorganization and inhibited topoisomerase-I activity. Although holamine and funtumine appear to have translational potential for the development of novel anticancer agents, further mechanistic and molecular studies are recommended to fully understand their anticancer effects.