Cargando…

SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against br...

Descripción completa

Detalles Bibliográficos
Autores principales: Zheng, Xiaowei, Wang, Changwei, Xing, Yuanming, Chen, Siying, Meng, Ti, You, Haisheng, Ojima, Iwao, Dong, Yalin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358697/
https://www.ncbi.nlm.nih.gov/pubmed/28197640
http://dx.doi.org/10.3892/ijo.2017.3871
_version_ 1782516259394420736
author Zheng, Xiaowei
Wang, Changwei
Xing, Yuanming
Chen, Siying
Meng, Ti
You, Haisheng
Ojima, Iwao
Dong, Yalin
author_facet Zheng, Xiaowei
Wang, Changwei
Xing, Yuanming
Chen, Siying
Meng, Ti
You, Haisheng
Ojima, Iwao
Dong, Yalin
author_sort Zheng, Xiaowei
collection PubMed
description Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. The aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms. The results of MTT assay showed that SB-T-121205 has much higher potency to human breast cancer cells (MCF-7/S, MCF-7/PTX and MDA-MB-453 cells) than paclitaxel, while that the non-tumorigenic human bronchial epithelial cells (BEAS-2B) were slightly less sensitive to SB-T-121205 than paclitaxel. Flow cytometry and western blot methods revealed that SB-T-121205 induced cell cycle arrest at the G2/M phase and apoptosis in MCF-7/PTX cells through accelerating mitochondrial apoptotic pathway, resulting in reduction of Bcl-2/Bax ratio, as well as elevation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) levels. Moreover, SB-T-121205 changed epithelial-mesenchymal transition (EMT) property, and suppressed migration and invasion abilities of MCF-7/PTX cells. Additionally, SB-T-121205 exerted antitumor activity by inhibiting the transgelin 2 and PI3K/Akt pathway. These findings indicate that SB-T-121205 is a potent antitumor agent that promotes apoptosis and also recedes migration/invasion abilities of MCF-7/PTX cells by restraining the activity of transgelin 2 and PI3K/Akt, as well as mitochondrial apoptotic pathway. Such results suggest a potential clinical value of SB-T-121205 in breast cancer treatment.
format Online
Article
Text
id pubmed-5358697
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-53586972017-04-06 SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells Zheng, Xiaowei Wang, Changwei Xing, Yuanming Chen, Siying Meng, Ti You, Haisheng Ojima, Iwao Dong, Yalin Int J Oncol Articles Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. The aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms. The results of MTT assay showed that SB-T-121205 has much higher potency to human breast cancer cells (MCF-7/S, MCF-7/PTX and MDA-MB-453 cells) than paclitaxel, while that the non-tumorigenic human bronchial epithelial cells (BEAS-2B) were slightly less sensitive to SB-T-121205 than paclitaxel. Flow cytometry and western blot methods revealed that SB-T-121205 induced cell cycle arrest at the G2/M phase and apoptosis in MCF-7/PTX cells through accelerating mitochondrial apoptotic pathway, resulting in reduction of Bcl-2/Bax ratio, as well as elevation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) levels. Moreover, SB-T-121205 changed epithelial-mesenchymal transition (EMT) property, and suppressed migration and invasion abilities of MCF-7/PTX cells. Additionally, SB-T-121205 exerted antitumor activity by inhibiting the transgelin 2 and PI3K/Akt pathway. These findings indicate that SB-T-121205 is a potent antitumor agent that promotes apoptosis and also recedes migration/invasion abilities of MCF-7/PTX cells by restraining the activity of transgelin 2 and PI3K/Akt, as well as mitochondrial apoptotic pathway. Such results suggest a potential clinical value of SB-T-121205 in breast cancer treatment. D.A. Spandidos 2017-02-10 /pmc/articles/PMC5358697/ /pubmed/28197640 http://dx.doi.org/10.3892/ijo.2017.3871 Text en Copyright © 2017, Spandidos Publications
spellingShingle Articles
Zheng, Xiaowei
Wang, Changwei
Xing, Yuanming
Chen, Siying
Meng, Ti
You, Haisheng
Ojima, Iwao
Dong, Yalin
SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells
title SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells
title_full SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells
title_fullStr SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells
title_full_unstemmed SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells
title_short SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells
title_sort sb-t-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in mcf-7/ptx cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358697/
https://www.ncbi.nlm.nih.gov/pubmed/28197640
http://dx.doi.org/10.3892/ijo.2017.3871
work_keys_str_mv AT zhengxiaowei sbt121205anextgenerationtaxaneenhancesapoptosisandinhibitsmigrationinvasioninmcf7ptxcells
AT wangchangwei sbt121205anextgenerationtaxaneenhancesapoptosisandinhibitsmigrationinvasioninmcf7ptxcells
AT xingyuanming sbt121205anextgenerationtaxaneenhancesapoptosisandinhibitsmigrationinvasioninmcf7ptxcells
AT chensiying sbt121205anextgenerationtaxaneenhancesapoptosisandinhibitsmigrationinvasioninmcf7ptxcells
AT mengti sbt121205anextgenerationtaxaneenhancesapoptosisandinhibitsmigrationinvasioninmcf7ptxcells
AT youhaisheng sbt121205anextgenerationtaxaneenhancesapoptosisandinhibitsmigrationinvasioninmcf7ptxcells
AT ojimaiwao sbt121205anextgenerationtaxaneenhancesapoptosisandinhibitsmigrationinvasioninmcf7ptxcells
AT dongyalin sbt121205anextgenerationtaxaneenhancesapoptosisandinhibitsmigrationinvasioninmcf7ptxcells