In Vitro Anticancer Properties of Novel Bis-Triazoles

• Published in: Current issues in molecular biology Vol. 45; no. 1; pp. 175 - 196
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 29.12.2022; MDPI AG
• Subjects: apoptosis assay; bis-triazoles; cell cycle analysis; G4-DNA; Hsp90; melanoma; Hsp90; senescence; apoptosis assay; NCI 60 cell line panel; melanoma; bis-triazoles; G4-DNA; cell cycle analysis
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb45010014

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.