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 journalArticle

35 Citations (Scopus)

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 G0 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
Pages (from-to)425-435
Number of pages11
JournalInvestigational New Drugs
Volume26
Issue number5
DOIs
Publication statusPublished - 10-2008

Fingerprint

Apoptosis
Breast Neoplasms
MCF-7 Cells
Growth
Pharmacology
Oxadiazoles
Heterocyclic Compounds
bcl-2-Associated X Protein
Cell Cycle Resting Phase
Oncogene Proteins
DNA Fragmentation
Caspase 3
Pharmaceutical Preparations
Chromatin
Cell Survival
Up-Regulation
1,3,4-oxadiazole
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Kumar, Akhilesh ; D'Souza, Saritha S. ; Gaonkar, S. L. ; Rai, K. M L ; Salimath, Bharathi P. / Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by a new series of substituted-1,3,4-oxadiazole derivatives. In: Investigational New Drugs. 2008 ; Vol. 26, No. 5. pp. 425-435.
@article{367d99477e034b949dd54f5a1123ef57,
title = "Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by a new series of substituted-1,3,4-oxadiazole derivatives",
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 G0 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.",
author = "Akhilesh Kumar and D'Souza, {Saritha S.} and Gaonkar, {S. L.} and Rai, {K. M L} and Salimath, {Bharathi P.}",
year = "2008",
month = "10",
doi = "10.1007/s10637-008-9116-5",
language = "English",
volume = "26",
pages = "425--435",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "5",

}

Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by a new series of substituted-1,3,4-oxadiazole derivatives. / Kumar, Akhilesh; D'Souza, Saritha S.; Gaonkar, S. L.; Rai, K. M L; Salimath, Bharathi P.

In: Investigational New Drugs, Vol. 26, No. 5, 10.2008, p. 425-435.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by a new series of substituted-1,3,4-oxadiazole derivatives

AU - Kumar, Akhilesh

AU - D'Souza, Saritha S.

AU - Gaonkar, S. L.

AU - Rai, K. M L

AU - Salimath, Bharathi P.

PY - 2008/10

Y1 - 2008/10

N2 - 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 G0 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.

AB - 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 G0 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.

UR - http://www.scopus.com/inward/record.url?scp=50249175985&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50249175985&partnerID=8YFLogxK

U2 - 10.1007/s10637-008-9116-5

DO - 10.1007/s10637-008-9116-5

M3 - Article

VL - 26

SP - 425

EP - 435

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 5

ER -