Impact of The Hybrid-Polar Histone Deacetylase Inhibitor M-Carboxycinnamic Acid Bis-Hydroxamide on Human Pancreatic Adenocarcinoma Cells.

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Impact of The Hybrid-Polar Histone Deacetylase Inhibitor M-Carboxycinnamic Acid Bis-Hydroxamide on Human Pancreatic Adenocarcinoma Cells.

Anticancer Agents Med Chem. 2018 Dec 31;:

Authors: Kumar D, Sarma P, Bhadra MP, Tangutur AD

Abstract
BACKGROUND: Histone deacetylase inhibitors (HDACIs) have got immense importance as promising drugs for cancer treatment as these inhibitors regulate cellular differentiation, gene expression, cell cycle arrest and apoptosis. The current study investigates the effect of the hybrid-polar HDACI m-carboxycinnamic acid bis-hydroxamide (CBHA) on the growth of human pancreatic adenocarcinoma, using the cell line MIA PaCa-2 as an in vitro model.
METHODS: Following CBHA treatment of the MIA PaCa-2 cells, we characterized the affect of CBHA by in vitro cytotoxicity evaluation, clonogenic assay, cell cycle analysis, immunoblotting for soluble and insoluble fractions of tubulin, immunofluorescence and caspase-3 assay.
RESULTS: We observed that the histone deacetylase inhibitor CBHA markedly impaired growth of the pancreatic cancer cells by resulting in dose dependent G2/M arrest, disruption of microtubule organization, induction of caspase mediated apoptosis and in vitro suppression of HDAC6. Our study also shows that inhibition of HDAC6 by CBHA as well induced acetylation of α-tubulin.
CONCLUSION: Together, our findings show that CBHA can be a potential plausible therapeutic that could be exploited for pancreatic cancer therapy.

PMID: 30621566 [PubMed - as supplied by publisher]

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