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Fulltext Growth inhibition and G2M cell cycle arrest induction by copper (II) complex on HT-29 human colon cancer cells

Sathiavani A., Vaisnevee S., Wong, Y. T., Foo, J. B., Low, M. L., Tor, Yin Sim

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):18-18.
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Introduction: Colon cancer is one of the leading cause of cancer death and current treatments often bring about undesired toxicities and resistance. Hence targeted therapeutic regimens for cancer are developed. Anticancer agent incorporated with copper has been synthesized to selectively target cancer cells that are reported to take up more copper compared to normal cells. Cu(SBCM)2 synthesized from the condensation of s-benzyldithiocarbazate and 3-aetylcoumarin was demonstrated to exhibit anti-proliferative effect towards MCF-7 cells and MDA-MB-231 breast cancer cells via cell cycle arrest and apoptosis. However, the mode of cell death of Cu(SBCM)2 on colon cancer cells has not been explored. This study investigated the anti-cancer properties of Cu(SBCM)2 on HT-29, colorectal cancer cell line. Methods: The growth inhibition of the copper complex was determined using MTT assay and xCELLigence real time cell monitoring analysis. Results: Cu(SBCM)2 was shown to inhibit the growth of HT-29 cells significantly in time- and dose- dependent manner with IC50 of 25.23 ± 8.22 uM at 48 hours. Morphological studies using inverted light microscope indicating Cu(SBCM)2-treated HT-29 cells displayed characteristics of apoptosis such as cellular shrinkage and membrane blebbing. Cell cycle analysis was carried out using flowcytometer and Cu(SBCM)2 was found to induce G2M cell cycle arrest at 24 and 48 hours. ROS assay was carried out to determine the involvement of oxidative stress on Cu(SBCM)2 treated HT-29 cells. Nevertheless, results indicated Cu(SBCM)2 significantly suppressed the formation of ROS compared to control. Conclusion: In summary, Cu(SBCM)2 shows promising potential in cancer therapy against colon cancer cells.
Induction of Apoptosis and Autophagy by Ternary Copper Complex Towards Breast Cancer Cells

Lee ZY, Leong CH, Lim KUL, Wong CCS, Pongtheerawan P, Arikrishnan SA, et al.

Anticancer Agents Med Chem, 2021 Jul 26.
PMID: 34315396 DOI: 10.2174/1871520621666210726132543

BACKGROUND: Copper complex has been gaining much attention in anticancer research as targeted agent since cancer cells uptake more copper than non-cancerous cells. Our group has synthesised a ternary copper complex which is composed of 1,10-phenanthroline and tyrosine [Cu(phen)(L-tyr)Cl].3H20. These two payloads are designed to cleave DNA and inhibit protein degradation system (proteasome) concurrently in cancer cells, making this copper complex a dual-target compound.
OBJECTIVE: Current study was carried out to investigate the mode of cell death and role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20 in MCF-7 and MDA-MB-231 breast cancer cells.
METHODS: Growth inhibition of [Cu(phen)(L-tyr)Cl].3H20 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 were 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].3H20.
RESULTS: [Cu(phen)(L-tyr)Cl].3H20 inhibited the growth of cancer cells dose-dependently with less toxicity towards MCF10A cells. Additionally, [Cu(phen)(L-tyr)Cl].3H20 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].3H20, indicating the induction of autophagy. Co-treatment with autophagy inhibitor hydroxychloroquine significantly enhanced growth inhibition of both cell lines, suggesting that the autophagy induced by [Cu(phen)(L-tyr) Cl].3H20 in both breast cancer cells was promoting cell survival.
CONCLUSION: [Cu(phen)(L-tyr)Cl].3H20 holds great potential to be developed for breast cancer treatment.

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