title: Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells.
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.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Fani
authors.affiliation: Medical Genetics Department, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran-Karaj Highway, Tehran, Iran.
authors.forename: Behnam
authors.initials: B
authors.lastname: Kamalidehghan
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kong Mun
authors.initials: KM
authors.lastname: Lo
authors.affiliation: Institute of Bioscience, University Putra Malaysia, 43400 Serdang, Malaysia.
authors.forename: Siamak Ebrahimi
authors.initials: SE
authors.lastname: Nigjeh
authors.affiliation: Institute of Bioscience, University Putra Malaysia, 43400 Serdang, Malaysia.
authors.forename: Yeap Swee
authors.initials: YS
authors.lastname: Keong
authors.affiliation: Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, 14174 Tehran, Iran.|Department of exercise science, Sports Center, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Dehghan
authors.affiliation: Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, 14174 Tehran, Iran.
authors.forename: Rahman
authors.initials: R
authors.lastname: Soori
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Mahmood Ameen
authors.initials: MA
authors.lastname: Abdulla
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kit May
authors.initials: KM
authors.lastname: Chow
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.|Center for Natural Products and Drug Discovery (CENAR), Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hapipah Mohd
authors.initials: HM
authors.lastname: Ali
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Hajiaghaalipour
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Elham
authors.initials: E
authors.lastname: Rouhollahi
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.|Center for Natural Products and Drug Discovery (CENAR), Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Najihah Mohd
authors.initials: NM
authors.lastname: Hashim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins