Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells

Fani, S. and Kamalidehghan, B. and Lo, Kong Mun and Nigjeh, S.E. and Keong, Y.S. and Dehghan, F. and Soori, R. and Abdulla, Mahmood Ameen and Chow, K.M. and Ali, Hapipah Mohd and Hajiaghaalipour, F. and Rouhollahi, E. and Hashim, N.M. (2016) Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells. Scientific Reports, 6. p. 38992. ISSN 2045-2322, DOI https://doi.org/10.1038/srep38992.

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Abstract

In the present study, we examined the cytotoxic effects of Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, and C1 on MDA-MB-231 cells and derived breast cancer stem cells from MDA-MB-231 cells. The acute toxicity experiment with compound C1 revealed no cytotoxic effects on rats. Fluorescent microscopic studies using Acridine Orange/Propidium Iodide (AO/PI) staining and flow cytometric analysis using an Annexin V probe confirmed the occurrence of apoptosis in C1-treated MDA-MB-231 cells. Compound C1 triggered intracellular reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) releases in treated MDA-MB-231 cells. The Cellomics High Content Screening (HCS) analysis showed the induction of intrinsic pathways in treated MDA-MB-231 cells, and a luminescence assay revealed significant increases in caspase 9 and 3/7 activity. Furthermore, flow cytometric analysis showed that compound C1 induced G0/G1 arrest in treated MDA-MB-231 cells. Real time PCR and western blot analysis revealed the upregulation of the Bax protein and the downregulation of the Bcl-2 and HSP70 proteins. Additionally, this study revealed the suppressive effect of compound C1 against breast CSCs and its ability to inhibit the Wnt/β-catenin signaling pathways. Our results demonstrate the chemotherapeutic properties of compound C1 against breast cancer cells and derived breast cancer stem cells, suggesting that the anticancer capabilities of this compound should be clinically assessed.

Item Type:	Article
Funders:	UNSPECIFIED
Uncontrolled Keywords:	Anticancer; Monobenzyltin complex C1; MDA-MB-231 cells; Induction; Apoptosis; Inhibition; Breast cancer stem cells
Subjects:	Q Science > Q Science (General) R Medicine
Divisions:	Faculty of Medicine Faculty of Science
Depositing User:	Ms. Juhaida Abd Rahim
Date Deposited:	14 Aug 2017 07:40
Last Modified:	30 Jan 2019 01:46
URI:	http://eprints.um.edu.my/id/eprint/17694

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