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

被引:43
作者
Kumar, Akhilesh [2 ]
D'Souza, Saritha S. [2 ]
Gaonkar, S. L. [3 ]
Rai, K. M. L. [3 ]
Salimath, Bharathi P. [1 ,2 ]
机构
[1] Univ Mysore, DOS Appl Bot & Biotechnol, Mysore 570006, Karnataka, India
[2] Univ Mysore, Dept Studies Biotechnol, Mysore 570006, Karnataka, India
[3] Univ Mysore, Dept Studies Chem, Mysore 570006, Karnataka, India
关键词
apoptosis; oxadiazole derivatives; MCF-7; cells; Bax; Bcl-2;
D O I
10.1007/s10637-008-9116-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:425 / 435
页数:11
相关论文
共 43 条
[1]
The Bcl-2 protein family: Arbiters of cell survival [J].
Adams, JM ;
Cory, S .
SCIENCE, 1998, 281 (5381) :1322-1326
[2]
Synthesis and anticonvulsant activity of new 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles [J].
Almasirad, A ;
Tabatabai, SA ;
Faizi, M ;
Kebriaeezadeh, A ;
Mehrabi, N ;
Dalvandi, A ;
Shafiee, A .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (24) :6057-6059
[3]
Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of some new 2-[(2,6-dichloroanilino) phenyl]acetic acid derivatives [J].
Amir, M ;
Shikha, K .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2004, 39 (06) :535-545
[4]
Apoptosis, cancer and cancer therapy [J].
Bold, RJ ;
Termuhlen, PM ;
McConkey, DJ .
SURGICAL ONCOLOGY-OXFORD, 1997, 6 (03) :133-142
[5]
THE ROLE OF DNA FRAGMENTATION IN APOPTOSIS [J].
BORTNER, CD ;
OLDENBURG, NBE ;
CIDLOWSKI, JA .
TRENDS IN CELL BIOLOGY, 1995, 5 (01) :21-26
[6]
BURBULIENE MM, 2004, 2 FARMACO, V59, P747
[7]
Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor α -: A new model for anti-estrogen resistance [J].
Campbell, RA ;
Bhat-Nakshatri, P ;
Patel, NM ;
Constantinidou, D ;
Ali, S ;
Nakshatri, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (13) :9817-9824
[8]
Prevention of breast cancer [J].
Carolin, KA ;
Pass, HA .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2000, 33 (03) :221-238
[9]
A review of breast cancer chemoprevention [J].
Chang, JCN .
BIOMEDICINE & PHARMACOTHERAPY, 1998, 52 (03) :133-136
[10]
EAMSHAW WC, 1999, ANNU REV BIOCHEM, V68, P383, DOI DOI 10.1146/ANNUREV.BI0CHEM.68.1383