<i>In Vitro</i> Anticancer Properties of Novel Bis-Triazoles

<i>In Vitro</i> Anticancer Properties of Novel Bis-Triazoles

Here, we describe the anticancer activity of our novel bis-triazoles <b>MS47</b> and <b>MS49</b>, 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 &l...

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Bibliographic Details
Main Authors: Maysaa M. Saleh, Duaa A. Abuarqoub, Alaa M. Hammad, Md Shahadat Hossan, Najneen Ahmed, Nazneen Aslam, Abdallah Y. Naser, Christopher J. Moody, Charles A. Laughton, Tracey D. Bradshaw
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Current Issues in Molecular Biology
Subjects:
apoptosis assay
bis-triazoles
cell cycle analysis
G4-DNA
Hsp90
melanoma
Online Access:https://www.mdpi.com/1467-3045/45/1/14
Description
Summary:Here, we describe the anticancer activity of our novel bis-triazoles <b>MS47</b> and <b>MS49</b>, 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 <b>MS47</b> (NCS 778438) was evaluated against a panel of sixty human cancer cell lines, and showed selective, distinct multi-log differential patterns of activity, with GI<sub>50</sub> and LC<sub>50</sub> values in the sub-micromolar range against human cancer cells. <b>MS47</b> showed highly selective cytotoxicity towards human melanoma, ovarian, CNS and colon cancer cell lines; in contrast, the leukemia cell lines interestingly showed resistance to <b>MS47</b> cytotoxic activity. Further studies revealed the potent cell growth inhibiting properties of <b>MS47</b> and <b>MS49</b> 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 <b>MS47</b> and <b>MS49</b>, and time- and dose-dependent apoptosis induction was also observed. Furthermore, <b>MS47</b> 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 <b>MS49</b>, 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.
ISSN:1467-3037
1467-3045

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