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J Breast Cancer. 2016 Dec;19(4):358-371. doi: 10.4048/jbc.2016.19.4.358. Epub 2016 Dec 23.

Alkyl Cinnamates Induce Protein Kinase C Translocation and Anticancer Activity against Breast Cancer Cells through Induction of the Mitochondrial Pathway of Apoptosis.

Journal of breast cancer

Suman Jyoti Deka, Narsimha Mamdi, Debasis Manna, Vishal Trivedi

Affiliations

  1. Malaria Research Group, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, India.
  2. Laboratory of Biological Chemistry, Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, India.

PMID: 28053624 PMCID: PMC5204042 DOI: 10.4048/jbc.2016.19.4.358

Abstract

PURPOSE: The protein kinase C (PKC) family of serine-threonine kinases plays an important role in cancer cell progression. Thus, molecules that target PKC have potential as anticancer agents. The current study aims to understand the treatment of breast cancer cells with alkyl cinnamates. We have also explored the mechanistic details of their anticancer action and the underlying molecular signaling.

METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to measure the viability of MDAMB-231 breast cancer cells to assess the anticancer activity of these compounds. In addition, flow cytometry was performed to study the effect of alkyl cinnamates on the cell cycle and apoptosis. Immunoblotting and immunofluorescence techniques were performed to study PKC translocation, cytochrome c release, and modulation of the mitochondrial membrane potential in breast cancer cells targeted with alkyl cinnamates.

RESULTS: The PKC agonist DM-2-8 translocated 16.6%±1.7% PKCα from cytosol to the plasma membrane and showed excellent anticancer activity with an half maximal inhibitory concentration (IC

CONCLUSION: Alkyl cinnamates specifically target cancer cells through induction of PKC translocation and the mitochondrial pathway of apoptosis, and could be promising anticancer drugs.

Keywords: Apoptosis; Caspases; Neoplasms; Oxidative stress; Protein kinase C

Conflict of interest statement

The authors declare that they have no competing interests.

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