MAY, a novel tubulin inhibitor, induces cell apoptosis in A549 and A549/Taxol cells and inhibits epithelial-mesenchymal transition in A549/Taxol cells.

Abstract

Non-small-cell lung cancer (NSCLC) is one of the common malignant tumors, and multidrug resistance (MDR) and tumor metastasis limit the anticancer effect of NSCLC. Therefore, it is necessary to develop new anticancer drug that can inhibit MDR and metastasis of NSCLC. In the present study, we found that 5-(2-chlorophenyl)-4-(4-(3,5-dimethoxyphenyl)piperazine-1-carbonyl)-2H-1,2,3- triazole (MAY) displayed strong cytotoxic effect on A549 and taxol-resistant A549 cells (A549/Taxol cells). We further discovered that MAY led to G2/M phase arrest by inhibiting microtubule polymerization in both cells. Then MAY caused apoptosis by the mitochondrial pathway in A549 cells and through the extrinsic pathway in A549/Taxol cells. Interestingly, MAY was not a substrate for P-glycoprotein (P-gp), which was highly expressed in A549/Taxol cells, and MAY inhibited the expression and efflux function of P-gp. Furthermore, MAY inhibited epithelial-mesenchymal transition (EMT) by targeting Twist1 in A549/Taxol cells. In summary, our results suggest that MAY induces apoptosis in A549 and A549/Taxol cells and inhibits EMT in A549/Taxol cells. These findings suggest that MAY could provide a promising method for the treatment of NSCLC, especially for the treatment of resistant NSCLC.

• Authors: Jianan Du, Jingnan Li, Minghuan Gao, Qi Guan, Tong Liu, Yue Wu, Zengqiang Li, Daiying Zuo, Weige Zhang, Yingliang Wu
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 323 Pg. 109074 (May 25 2020) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 32217108 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Nuclear Proteins
• TWIST1 protein, human
• Triazoles
• Tubulin Modulators
• Twist-Related Protein 1
• Paclitaxel

Topics

• A549 Cells
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Survival (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Humans
• Inhibitory Concentration 50
• Microtubules (drug effects, metabolism)
• Mitochondria (drug effects, metabolism)
• Nuclear Proteins (metabolism)
• Paclitaxel (chemistry, pharmacology)
• Polymerization
• Signal Transduction (drug effects)
• Triazoles (chemistry, pharmacology)
• Tubulin Modulators (chemistry, pharmacology)
• Twist-Related Protein 1 (metabolism)