title: A Schiff base-derived copper (II) complex is a potent inducer of apoptosis in colon cancer cells by activating the intrinsic pathway.
abstract: Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87  μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25  μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia ; Faculty of Science, Institute of Biological Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hajrezaie
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Mohammadjavad
authors.initials: M
authors.lastname: Paydar
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Soheil Zorofchian
authors.initials: SZ
authors.lastname: Moghadamtousi
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Pouya
authors.initials: P
authors.lastname: Hassandarvish
authors.affiliation: Department of Chemistry, University of Malaya, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Nura Suleiman
authors.initials: NS
authors.lastname: Gwaram
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia ; Faculty of Science, Institute of Biological Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zahedifard
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 Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Hamed
authors.initials: H
authors.lastname: Karimian
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Chung Yeng
authors.initials: CY
authors.lastname: Looi
authors.affiliation: Department of Chemistry, University of Malaya, University of Malaya, 50603 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: Nazia
authors.initials: N
authors.lastname: Abdul Majid
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
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D003300:Copper / Q000737:chemistry*; D045304:Cytochromes c / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D003300:Copper; D045304:Cytochromes c; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9
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