Induction of Apoptosis and Autophagy by Ternary Copper Complex Towards Breast Cancer Cells.

Autor:	Lee ZY; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Leong CH; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Lim KUL; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Wong CCS; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Pongtheerawan P; School of Pharmacy, Walailak University, 222, Thai Buri, Tha Sala District, Nakhon Si Thammarat, 80160, Thailand., Arikrishnan SA; School of Biosciences, Faculty of Health and Medical Sciences, Taylor\'s University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Tan KL; School of Biosciences, Faculty of Health and Medical Sciences, Taylor\'s University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Loh JS; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Low ML; International Medical University, Department of Pharmaceutical Chemistry, School of Pharmacy, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia., How CW; School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia., Ong YS; School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia., Tor YS; School of Biosciences, Faculty of Health and Medical Sciences, Taylor\'s University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.; Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health & Medical Sciences, Taylor's University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Foo JB; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.; Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health & Medical Sciences, Taylor's University, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
Jazyk:	angličtina
Zdroj:	Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2022; Vol. 22 (6), pp. 1159-1170.
DOI:	10.2174/1871520621666210726132543
Abstrakt:	Background: Copper complex has been gaining much attention in anticancer research as a targeted agent since cancer cells uptake more copper than non-cancerous cells. Our group synthesised a ternary copper complex, which is composed of 1,10-phenanthroline and tyrosine [Cu(phen)(L-tyr)Cl].3H 2 0. These two payloads have been designed to cleave DNA and inhibit protein degradation system (proteasome) concurrently in cancer cells, making this copper complex a dual-target compound. Objective: The current study was carried out to investigate the mode of cell death and the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H 2 0 in MCF-7 and MDA-MB-231 breast cancer cells. Methods: Growth inhibition of [Cu(phen)(L-tyr)Cl].3H 2 0 towards MDA-MB-231 and human non-cancerous MCF10A breast cells was determined by MTT assay. Annexin-V-FITC/PI and cell cycle analysis were evaluated by flow cytometry. The expression of p53, Bax, caspase-9, caspase-7, caspase-3 and LC3 was determined using western blot analysis. The cells were then co-treated with hydroxychloroquine to ascertain the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H 2 0. Results: [Cu(phen)(L-tyr)Cl].3H 2 0 inhibited the growth of cancer cells dose-dependently with less toxicity towards MCF10A cells. Additionally, [Cu(phen)(L-tyr)Cl].3H 2 0 induced apoptosis and cell cycle arrest towards MCF-7 and MDA-MB-231 breast cancer cells possibly via regulation of p53, Bax, caspase-9, caspase-3 and capase-7. The expression of LC3II was upregulated in both cancer cell lines upon treatment with [Cu(phen)(L-tyr) Cl].3H 2 0, indicating the induction of autophagy. Co-treatment with autophagy inhibitor hydroxychloroquine significantly enhanced growth inhibition of both cell lines, suggesting that autophagy induced by [Cu(phen)(L-tyr) Cl].3H 2 0 in both breast cancer cells promoted cell survival. Conclusion: [Cu(phen)(L-tyr)Cl].3H 2 0 holds great potential to be developed for breast cancer treatment. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu