Copper complex derived from <Emphasis Type="Italic">S</Emphasis>-benzyldithiocarbazate and 3-acetylcoumarin induced apoptosis in breast cancer cell |
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| Authors: | Jhi Biau Foo May Lee Low Ji Hui Lim Yan Zhi Lor Rusyidah Zainol Abidin Vilasini Eh Dam Napsiah Abdul Rahman Chaw Yee Beh Lee Chin Chan Chee Wun How Yin Sim Tor Latifah Saiful Yazan |
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| Institution: | 1.Faculty of Pharmacy,MAHSA University,Jenjarom,Malaysia;2.School of Pharmacy, Faculty of Health & Medical Sciences,Taylor’s University,Subang Jaya,Malaysia;3.Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University,Bukit Jalil,Malaysia;4.Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience,Universiti Putra Malaysia (UPM),Serdang,Malaysia;5.Virology Lab 1, Faculty of Biotechnology and Biomolecular Sciences,Universiti Putra Malaysia (UPM),Serdang,Malaysia;6.School of Biosciences, Faculty of Health & Medical Sciences,Taylor’s University,Subang Jaya,Malaysia;7.Department of Biomedical Sciences, Faculty of Medicine and Health Sciences,Universiti Putra Malaysia (UPM),Serdang,Malaysia |
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| Abstract: | Copper complexes have been widely studied for the anti-tumour application as cancer cells are reported to take up greater amounts of copper than normal cells. Preliminary study revealed that the newly synthesised copper complex Cu(SBCM)2] displayed marked anti-proliferative towards triple-negative MDA-MB-231 breast cancer cells. Therefore, Cu(SBCM)2 has great potential to be developed as an agent for the management of breast cancer. The present study was carried out to investigate the mode of cell death induced by Cu(SBCM)2 towards MDA-MB-231 breast cancer cells. The inhibitory and morphological changes of MDA-MB-231 cells treated with Cu(SBCM)2 was determined by using MTT assay and inverted light microscope, respectively. The safety profile of Cu(SBCM)2 was also evaluated towards human dermal fibroblast (HDF) normal cells. Confirmation of apoptosis and cell cycle arrest were determined by flow cytometry analysis. The expression of p53, Bax, Bcl-2 and MMP2 protein were detected with western blot analysis. Cu(SBCM)2 significantly inhibited the growth of MDA-MB-231 cells in a dose-dependent manner with GI50 18.7?±?3.06 µM. Indeed, Cu(SBCM)2 was less toxic towards HDF normal cells with GI50 31.8?±?4.0 µM. Morphological study revealed that Cu(SBCM)2-treated MDA-MB-231 cells experienced cellular shrinkage, membrane blebbing, chromatin condensation and formation of apoptotic bodies, suggesting that Cu(SBCM)2 induced apoptosis in the cells, which was confirmed by Annexin-V/PI flow cytometry analysis. It was also found that Cu(SBCM)2 induced G2/M phase cell cycle arrest towards MDA-MB-231 cells. The induction of apoptosis and cell cycle arrest in the present study is possibly due to the down-regulation of the mutant p53 and MMP2 protein. In conclusion, Cu(SBCM)2 can be developed as a targeted therapy for the treatment of triple-negative breast cancer. |
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