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2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ0814061), a novel microtubule inhibitor, evokes G2/M cell cycle arrest and apoptosis in human breast cancer cells.
Biomed Pharmacother. 2016 Mar; 78:308-321.BP

Abstract

Breast cancer is the leading cause of cancer death in women worldwide, and novel chemotherapeutic drugs with high activity and no drug resistance for treating breast cancer are needed urgently. In this study, we investigated the antitumor effect of 2-methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ0814061), which has a strong inhibition of cell growth in MCF-7 and MDA-MB-231 cells. We demonstrated that SQ0814061 (SQ) time-dependently induced cell cycle arrest at G2/M phase and subsequently progressed into apoptosis, which is associated with microtubule depolymerization. Western blot analysis revealed that up-regulation of cyclin B1 and Aurora A was related with G2/M phase arrest in MCF-7 and MDA-MB-231 cells treatment with SQ. However, the formation of multinucleated cells after a long time exposed to SQ of MCF-7 cells delayed the cell death. In addition, apoptosis induced by SQ is correlated with the down-regulation of the PI3K-Akt-MDM2 pathway in MCF-7 and MDA-MB-231 cells. Treatment with the PI3K specific inhibitor, LY294002, increased SQ-induced cell growth inhibitory rate and apoptosis rate of MCF-7 and MDA-MB-231 cells. Moreover, SQ induced MCF-7 and MDA-MB-231 cells to generate reactive oxygen species (ROS), and the SQ-induced cell death was ROS dependent. In conclusion, all the data demonstrated that SQ exhibited its antitumor activity through disrupting the microtubule assembly, inducing cell cycle arrest and eventually apoptosis which is associated with PI3K-Akt-MDM2 pathway in MCF-7 and MDA-MB-231 cells. Therefore, the novel compound SQ is a promising microtubule inhibitor that has tremendous potentials for therapeutic treatment of human mastocarcinoma.

Authors+Show Affiliations

Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: zhangweige2000@sina.com.Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: yingliang_1016@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26898456

Citation

Xu, Jingwen, et al. "2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) Phenol (SQ0814061), a Novel Microtubule Inhibitor, Evokes G2/M Cell Cycle Arrest and Apoptosis in Human Breast Cancer Cells." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 78, 2016, pp. 308-321.
Xu J, Zuo D, Qi H, et al. 2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ0814061), a novel microtubule inhibitor, evokes G2/M cell cycle arrest and apoptosis in human breast cancer cells. Biomed Pharmacother. 2016;78:308-321.
Xu, J., Zuo, D., Qi, H., Shen, Q., Bai, Z., Han, M., Li, Z., Zhang, W., & Wu, Y. (2016). 2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ0814061), a novel microtubule inhibitor, evokes G2/M cell cycle arrest and apoptosis in human breast cancer cells. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 78, 308-321. https://doi.org/10.1016/j.biopha.2016.01.040
Xu J, et al. 2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) Phenol (SQ0814061), a Novel Microtubule Inhibitor, Evokes G2/M Cell Cycle Arrest and Apoptosis in Human Breast Cancer Cells. Biomed Pharmacother. 2016;78:308-321. PubMed PMID: 26898456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ0814061), a novel microtubule inhibitor, evokes G2/M cell cycle arrest and apoptosis in human breast cancer cells. AU - Xu,Jingwen, AU - Zuo,Daiying, AU - Qi,Huan, AU - Shen,Qirong, AU - Bai,Zhaoshi, AU - Han,Mengting, AU - Li,Zengqiang, AU - Zhang,Weige, AU - Wu,Yingliang, Y1 - 2016/02/06/ PY - 2015/09/13/received PY - 2016/01/26/accepted PY - 2016/2/23/entrez PY - 2016/2/24/pubmed PY - 2016/12/15/medline KW - Apoptosis KW - Breast cancer KW - Combretastatin A-4 KW - G2/M arrest KW - MDM2 SP - 308 EP - 321 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 78 N2 - Breast cancer is the leading cause of cancer death in women worldwide, and novel chemotherapeutic drugs with high activity and no drug resistance for treating breast cancer are needed urgently. In this study, we investigated the antitumor effect of 2-methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ0814061), which has a strong inhibition of cell growth in MCF-7 and MDA-MB-231 cells. We demonstrated that SQ0814061 (SQ) time-dependently induced cell cycle arrest at G2/M phase and subsequently progressed into apoptosis, which is associated with microtubule depolymerization. Western blot analysis revealed that up-regulation of cyclin B1 and Aurora A was related with G2/M phase arrest in MCF-7 and MDA-MB-231 cells treatment with SQ. However, the formation of multinucleated cells after a long time exposed to SQ of MCF-7 cells delayed the cell death. In addition, apoptosis induced by SQ is correlated with the down-regulation of the PI3K-Akt-MDM2 pathway in MCF-7 and MDA-MB-231 cells. Treatment with the PI3K specific inhibitor, LY294002, increased SQ-induced cell growth inhibitory rate and apoptosis rate of MCF-7 and MDA-MB-231 cells. Moreover, SQ induced MCF-7 and MDA-MB-231 cells to generate reactive oxygen species (ROS), and the SQ-induced cell death was ROS dependent. In conclusion, all the data demonstrated that SQ exhibited its antitumor activity through disrupting the microtubule assembly, inducing cell cycle arrest and eventually apoptosis which is associated with PI3K-Akt-MDM2 pathway in MCF-7 and MDA-MB-231 cells. Therefore, the novel compound SQ is a promising microtubule inhibitor that has tremendous potentials for therapeutic treatment of human mastocarcinoma. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/26898456/2_Methoxy_5__345_trimethosyphenyl_seleninyl__phenol__SQ0814061__a_novel_microtubule_inhibitor_evokes_G2/M_cell_cycle_arrest_and_apoptosis_in_human_breast_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(15)30155-4 DB - PRIME DP - Unbound Medicine ER -