title: Apoptotic effect of novel Schiff based CdCl₂(C₁₄H₂₁N₃O₂) complex is mediated via activation of the mitochondrial pathway in colon cancer cells.
abstract: The development of metal-based agents has had a tremendous role in the present progress in cancer chemotherapy. One well-known example of metal-based agents is Schiff based metal complexes, which hold great promise for cancer therapy. Based on the potential of Schiff based complexes for the induction of apoptosis, this study aimed to examine the cytotoxic and apoptotic activity of a CdCl2(C14H21N3O2) complex on HT-29 cells. The complex exerted a potent suppressive effect on HT-29 cells with an IC50 value of 2.57 ± 0.39 after 72 h of treatment. The collapse of the mitochondrial membrane potential and the elevated release of cytochrome c from the mitochondria to the cytosol indicate the involvement of the intrinsic pathway in the induction of apoptosis. The role of the mitochondria-dependent apoptotic pathway was further proved by the significant activation of the initiator caspase-9 and the executioner caspases-3 and -7. In addition, the activation of caspase-8, which is associated with the suppression of NF-κB translocation to the nucleus, also revealed the involvement of the extrinsic pathway in the induced apoptosis. The results suggest that the CdCl2(C14H21N3O2) complex is able to induce the apoptosis of colon cancer cells and is a potential candidate for future cancer studies.
authors.affiliation: 1] Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia [2] Institute of Biological Science, Faculty of 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 Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Chung Yeng
authors.initials: CY
authors.lastname: Looi
authors.affiliation: Institute of Biological Science, Faculty of Science, 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, 50603 Kuala Lumpur, Malaysia.
authors.forename: Muhammad Saleh
authors.initials: MS
authors.lastname: Salga
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Hamed
authors.initials: H
authors.lastname: Karimian
authors.affiliation: Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Keivan
authors.initials: K
authors.lastname: Shams
authors.affiliation: 1] Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia [2] Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zahedifard
authors.affiliation: Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Nazia Abdul
authors.initials: NA
authors.lastname: Majid
authors.affiliation: Department of Chemistry, 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: Mahmood Ameen
authors.initials: MA
authors.lastname: Abdulla
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019256:Cadmium Chloride / Q000737:chemistry* / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D012545:Schiff Bases; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012545:Schiff Bases; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D020169:Caspases; D020782:Matrix Metalloproteinases; D019256:Cadmium Chloride