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Downregulation of HSP27 by isoindole-derived pyrrolidines suppressing multidrug resistance (MDR) and inducing apoptosis in MCF-7 and DLD-1 cell lines

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Title Downregulation of HSP27 by isoindole-derived pyrrolidines suppressing multidrug resistance (MDR) and inducing apoptosis in MCF-7 and DLD-1 cell lines
 
Creator Mesci, Seda
Yazgan, Burak
Gül, Melek
Yıldırım, Tuba
 
Subject Breast cancer
Colon cancer
Heat shock proteins (HSPs)
Isoindole
 
Description 254-265
In most cancer treatments, major problem arises from the prevention of cell death (apoptosis suppression) with the development
of drug resistance. Anticancer agents that ensure elimination of drug resistance and drug-resistant cells to apoptosis, are among the
main targets. Here, we evaluated a series of synthesized N-phenyl maleimide substituents in tetracyclic compounds as anticancer
drug candidate. We selected compounds may lead to death and eliminate drug resistance in breast and colon cells. In MCF-7 and
DLD-1 cell lines; multidrug resistance genes (ABCB1, ABCC3, ABCC10, ABCC11 and ABCG2), apoptosis mechanism genes
(BAX, BCL-2, p53, PARP and CASP3), heat shock genes (HSP27, HSP40, HSP60, HSP70 and HSP90α) and endoplasmic
reticulum (ER) chaperone genes (GRP78 and GRP94) mRNA levels were determined by qPCR method. Amounts of proteins of
apoptosis and signalling pathways were measured by human apoptosis antibody array. The compounds have been shown to have
downregulation on multidrug resistance genes other than ABCC3. It was found that all compounds in MCF-7 and DLD-1 cells
showed significant increase in p53, BAX and CASP3 gene expressions. Also, the compounds have the potential to reduce gene
expression of heat shock genes (HSPs). While the compounds have been determined to increase protein expression in BAD,
BAX, BID, BIM, Caspase-3, Caspase-7, Caspase-8, Cytochrome-C, Fas, TNF, TRAIL, p27, p38 and p53; decrease protein
expression in AKT, BCL-2, ERK1/2, HSP27, HSP60, IGFs, JNK, NFKB, PARP, TAK1, Survivin in MCF-7 and DLD-1 cells. The
compounds stand out with their inhibition of HSP27 in DLD-1 cells and their inhibition with HSP27 and NFB in MCF-7 cells.
Overall, it has been shown that these compounds increase intrinsic and extrinsic proapoptotic proteins, decrease antiapoptotic
proteins, decrease HSPs and some growth factors, and they may serve as potential anticarcinogenic molecules.
 
Date 2024-03-27T05:52:39Z
2024-03-27T05:52:39Z
2024-04
 
Type Article
 
Identifier 0975-1009 (Online); 0019-5189 (Print)
http://nopr.niscpr.res.in/handle/123456789/63622
https://doi.org/10.56042/ijeb.v62i04.982
 
Language en
 
Publisher NIScPR-CSIR, India
 
Source IJEB Vol.62(04) [April 2024]