Genotoxicity and apoptotic effect of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine on malignant melanoma cells, SK-MEL-28

Ooi, Theng Choon and Nordin, Fariza Juliana and Rahmat, Nur Sakina and Halim, Syahrina Nur `Ain Abdul and Sarip, Rozie and Chan, Kok Meng and Rajab, Nor Fadilah (2023) Genotoxicity and apoptotic effect of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine on malignant melanoma cells, SK-MEL-28. Mutation Research-Genetic Toxicology and Environmental Mutagenesis, 886. ISSN 1383-5718, DOI https://doi.org/10.1016/j.mrgentox.2022.503581.

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Abstract

Complexes of coinage metals can potentially be used as alternatives to platinum-based chemotherapeutic drugs. Silver is a coinage metal that can potentially improve the spectrum of efficacy in various cancers treatment, such as malignant melanoma. Melanoma is the most aggressive form of skin cancer that is often diagnosed in young and middle-aged adults. Silver has high reactivity with skin proteins and can be developed as a malignant melanoma treatment modality. Therefore, this study aims to identify the anti-proliferative and genotoxic effects of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine ligands in the human melanoma SK-MEL-28 cell line. The anti-proliferative effects of a series of silver(I) complex compounds labelled as OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were evaluated on SK-MEL-28 cells by using the Sulforhodamine B assay. Then, DNA damage analysis was performed in a time-dependent manner (30 min, 1 h and 4 h) by using alkaline comet assay to investigate the genotoxicity of OHBT and BrOHMBT at their respective IC50 values. The mode of cell death was studied using Annexin V-FITC/PI flow cytometry assay. Our current findings demonstrated that all silver(I) complex compounds showed good anti-proliferative activity. The IC50 values of OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were 2.38 +/- 0.3 mu M, 2.70 +/- 0.17 mu M, 1.34 +/- 0.22 mu M, 2.82 +/- 0.45 mu M, and 0.64 +/- 0.04 mu M respectively. Then, DNA damage analysis showed that OHBT and BrOHMBT could induce DNA strand breaks in a time-dependent manner, with OHBT being more prominent than BrOHMBT. This effect was accompanied by apoptosis induction in SK-MEL-28, as evaluated using Annexin VFITC/PI assay. In conclusion, silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(ptolyl)phosphine exerted anti-proliferative activities by inhibiting cancer cell growth, inducing significant DNA damage and ultimately resulting in apoptosis.

Item Type: Article
Funders: Ministry of Education, Malaysia (Grant No: FRGS/1/2019/STG04/UKM/01/1), Univesiti Kebangsaan Malaysia (Grant No: DIP -2021-023)
Uncontrolled Keywords: Anti-proliferative; Apoptosis; Genotoxic; Silver(I) complexes; SK-MEL-28 melanoma cells
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Ms Zaharah Ramly
Date Deposited: 30 Nov 2023 07:44
Last Modified: 30 Nov 2023 07:44
URI: http://eprints.um.edu.my/id/eprint/38882

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