Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by a new series of substituted-1,3,4-oxadiazole derivatives

Akhilesh Kumar, Saritha S D'Souza, S L Gaonkar, K M L Rai, Bharathi P Salimath

Research output: Contribution to journalArticlepeer-review

Abstract

The multiple pharmacological actions of unique synthetic compounds are a prerequisite for classifying a drug as highly efficacious, because the multiple pharmacological actions offer the possibility of treating various diseases like cancer. 1,3,4-Oxadiazoles are an important class of heterocyclic compounds with broad spectrum of biological activities. In this study we focused on the ability of these derivatives to induce apoptosis in cultured MCF-7 breast cancer cells. Treatment of MCF-7 cells with varying concentrations of the different derivatives resulted in dose and time dependent sequence of events marked by apoptosis, as shown by loss of cell viability, chromatin condensation, internucleosomal DNA fragmentation and sub G(0) phase accumulation. Furthermore, apoptosis in MCF-7 cell was induced by upregulation of proto-oncoprotein Bax and activation of Caspase-3 activated DNase. Although the derivatives induced apoptosis was associated with Bax protein levels, negligible Bcl-2 reduction was observed. Analysis of the data suggests that the substituted oxadiazole derivatives exert antiproliferative action and growth inhibition on MCF-7 cells through apoptosis induction and that it may have anticancer properties valuable for application in drug products.

Original languageEnglish (US)
Pages (from-to)425-35
Number of pages11
JournalInvestigational New Drugs
Volume26
Issue number5
DOIs
StatePublished - Oct 2008

Keywords

  • Antineoplastic Agents/therapeutic use
  • Apoptosis/drug effects
  • Breast Neoplasms/drug therapy
  • Caspase 3/pharmacology
  • Cell Cycle/drug effects
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • DNA Fragmentation
  • Deoxyribonucleases/metabolism
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Oxadiazoles/therapeutic use
  • Proto-Oncogene Proteins c-bcl-2/metabolism
  • bcl-2-Associated X Protein/metabolism

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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