In Vitro Anticancer Properties of Novel Bis-Triazoles

Saleh, Maysaa M.; Abuarqoub, Duaa A.; Hammad, Alaa M.; Hossan, Md Shahadat; Ahmed, Najneen; Aslam, Nazneen; Naser, Abdallah Y.; Moody, Christopher J.; Laughton, Charles A.; Bradshaw, Tracey D.

Abstract

Here, we describe the anticancer activity of our novel bis-triazoles MS47 and MS49, developed previously as G-quadruplex stabilizers, focusing specifically upon the human melanoma MDA-MB-435 cell line. At the National Cancer Institute (NCI), USA, bis-triazole MS47 (NCS 778438) was evaluated against a panel of sixty human cancer cell lines, and showed selective, distinct multi-log differential patterns of activity, with GI50 and LC50 values in the sub-micromolar range against human cancer cells. MS47 showed highly selective cytotoxicity towards human melanoma, ovarian, CNS and colon cancer cell lines; in contrast, the leukemia cell lines interestingly showed resistance to MS47 cytotoxic activity. Further studies revealed the potent cell growth inhibiting properties of MS47 and MS49 against the human melanoma MDA-MB-435 cell line, as verified by MTT assays; both ligands were more potent against cancer cells than MRC-5 fetal lung fibroblasts (SI > 9). Melanoma colony formation was significantly suppressed by MS47 and MS49, and time- and dose-dependent apoptosis induction was also observed. Furthermore, MS47 significantly arrested melanoma cells at the G0/G1 cell cycle phase. While the expression levels of Hsp90 protein in melanoma cells were significantly decreased by MS49, corroborating its binding to the G4-DNA promoter of the Hsp90 gene. Both ligands failed to induce senescence in the human melanoma cells after 72 h of treatment, corroborating their weak stabilization of the telomeric G4-DNA.

Citation

Saleh, M. M., Abuarqoub, D. A., Hammad, A. M., Hossan, M. S., Ahmed, N., Aslam, N., Naser, A. Y., Moody, C. J., Laughton, C. A., & Bradshaw, T. D. (2023). In Vitro Anticancer Properties of Novel Bis-Triazoles. Current Issues in Molecular Biology, 45(1), 175-196. https://doi.org/10.3390/cimb45010014

• Journal Article Type: Article
• Acceptance Date: Dec 8, 2022
• Online Publication Date: Dec 29, 2022
• Publication Date: 2023-01
• Deposit Date: Jan 3, 2023
• Publicly Available Date: Jan 9, 2023
• Journal: Current Issues in Molecular Biology
• Print ISSN: 1467-3037
• Electronic ISSN: 1467-3045
• Publisher: Horizon Scientific Press
• Peer Reviewed: Peer Reviewed
• Volume: 45
• Issue: 1
• Pages: 175-196
• DOI: https://doi.org/10.3390/cimb45010014
• Keywords: Article, apoptosis assay, bis-triazoles, cell cycle analysis, G4-DNA, Hsp90, melanoma, NCI 60 cell line panel, senescence
• Public URL: https://nottingham-repository.worktribe.com/output/15436709