Overcoming resistance to mitochondrial apoptosis by BZML-induced mitotic catastrophe is enhanced by inhibition of autophagy in A549/Taxol cells

Cell Proliferation
Zhaoshi BaiYingliang Wu

Abstract

Our previous in vitro study showed that 5-(3, 4, 5-trimethoxybenzoyl)-4-methyl-2-(p-tolyl) imidazol (BZML) is a novel colchicine binding site inhibitor with potent anti-cancer activity against apoptosis resistance in A549/Taxol cells through mitotic catastrophe (MC). However, the mechanisms underlying apoptosis resistance in A549/Taxol cells remain unknown. To clarify these mechanisms, in the present study, we investigated the molecular mechanisms of apoptosis and autophagy, which are closely associated with MC in BZML-treated A549 and A549/Taxol cells. Xenograft NSCLC models induced by A549 and A549/Taxol cells were used to evaluate the efficacy of BZML in vivo. The activation of the mitochondrial apoptotic pathway was assessed using JC-1 staining, Annexin V-FITC/PI double-staining, a caspase-9 fluorescence metric assay kit and western blot. The different functional forms of autophagy were distinguished by determining the impact of autophagy inhibition on drug sensitivity. Our data showed that BZML also exhibited desirable anti-cancer activity against drug-resistant NSCLC in vivo. Moreover, BZML caused ROS generation and MMP loss followed by the release of cytochrome c from mitochondria to cytosol in both A549 and A549/Taxol c...Continue Reading

References

Apr 30, 2011·Nature Reviews. Molecular Cell Biology·Ilio VitaleGuido Kroemer
Apr 11, 2012·International Journal of Molecular Sciences·Marijke JozefczakAnn Cuypers
Jun 15, 2013·Oxidative Medicine and Cellular Longevity·Nicola TraversoCinzia Domenicotti
Oct 15, 2013·Autophagy·Amber N HaleEdmund B Rucker
May 31, 2014·Biochemical Pharmacology·Doriane LorendeauHélène Baubichon-Cortay
May 31, 2014·Biochemical Pharmacology·David A Gewirtz
May 6, 2015·Seminars in Cancer Biology·Ramzi M MohammadAsfar S Azmi
Sep 10, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Cheng ZhangChengchao Shou
Sep 27, 2015·Free Radical Biology & Medicine·Subhadip MukhopadhyaySujit Kumar Bhutia
Oct 23, 2015·Mediators of Inflammation·Margaret M Mc Gee
Jan 9, 2016·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Jan 26, 2016·CA: a Cancer Journal for Clinicians·Wanqing ChenJie He
Feb 3, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Tatiana V DenisenkoBoris Zhivotovsky
Jun 3, 2016·CA: a Cancer Journal for Clinicians·Kimberly D MillerAhmedin Jemal
Jun 28, 2016·Oncotarget·Clarissa Ribeiro Reily RochaCarlos Frederico Martins Menck
Oct 25, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ewa DrozdBeata Gruber-Bzura
Oct 21, 2016·Autophagy·Ya-Qin TanGang Zhou
Nov 30, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Wenhua Zhang, Xueqian Shao
Feb 23, 2017·Scientific Reports·Xu-Shun JiangXiao-Gang Du
Apr 12, 2017·Seminars in Cell & Developmental Biology·Richard W Birkinshaw, Peter E Czabotar
Apr 27, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiaoli ShiCong Wang
May 14, 2017·Cancer Chemotherapy and Pharmacology·Yen-Yun WangShyng-Shiou F Yuan
May 23, 2017·Biochemical and Biophysical Research Communications·Minghao WangJun Jiang
May 23, 2017·Translational Lung Cancer Research·Jyoti MalhotraJoseph Aisner
Jul 6, 2017·International Journal of Molecular Sciences·Amelia L ParkerMaria Kavallaris

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms