title: Enhanced stability of microtubules contributes in the development of colchicine resistance in MCF-7 cells.
abstract: Understanding the mechanism of resistance to tubulin-targeted anticancer drugs is important for improved chemotherapy. In this work, a colchicine-resistant MCF-7 cell line (MCF-7Col30) was generated by the gradual increment of colchicine treatment and the MCF-7Col30showed ∼8-fold resistance towards colchicine. MCF-7Col30cells showed ∼2.5-fold resistance against microtubule depolymerizing agents, vinblastine, and nocodazole. In contrast, it displayed more sensitivity towards paclitaxel, a microtubule-polymerizing agent. MCF-7 and MCF-7Col30cells showed similar sensitivity towards cisplatin. Further, the level of P-glycoprotein did not increase in MCF-7Col30cells. MCF-7Col30cells resisted the microtubule depolymerizing effects of colchicine. The time-lapse imaging of individual microtubules in live cells showed that the dynamics of microtubules in MCF-7Col30cells was suppressed as compared to the parent MCF-7 cells. The levels of tubulin acetylation and glutamylation increased in MCF-7Col30cells than the parent MCF-7 cells suggesting that microtubules are stabilized in MCF-7Col30cells. Interestingly, the level of βIII tubulin was increased by 2.3 folds whereas that of βII and βIV tubulin was decreased by 55 and 150%, respectively in MCF-7Col30cells. The results suggested that the changes in the level of β-tubulin isoforms and the post-translational modifications of microtubules altered the stability and dynamics of microtubules and contributed to the development of colchicine-resistance in MCF-7 cells.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Rai
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India.
authors.forename: Sonia
authors.initials: S
authors.lastname: Kapoor
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India.
authors.forename: Afsana
authors.initials: A
authors.lastname: Naaz
authors.affiliation: National Centre for Cell Science, University of Pune Campus, Ganeshkhind, Pune, Maharashtra 411007, India.
authors.forename: Manas
authors.initials: M
authors.lastname: Kumar Santra
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India. Electronic address: panda@iitb.ac.in.
authors.forename: Dulal
authors.initials: D
authors.lastname: Panda
mesh_terms: D000107:Acetylation; D001943:Breast Neoplasms / Q000473:pathology; D003078:Colchicine / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008870:Microtubules / Q000378:metabolism*; D009154:Mutation; D017239:Paclitaxel / Q000494:pharmacology; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D014404:Tubulin; D018698:Glutamic Acid; D017239:Paclitaxel; D003078:Colchicine
keywords: Colchicine; Drug resistance; Microtubule dynamics; Microtubule stability; Tubulin isotypes