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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Explorations of ATP-Binding Cassette Transporters and Apoptosis Signal Pathways of 2-Hydroxyanthraquinone Substituted Cyclotriphosphazenes in MCF-7 and DLD-1 Cell Lines

Author(s): Burak Yazgan, Seda Mesci, Nagihan Bayık, Maşuk Akşahin, Gönül Yenilmez Çiftçi* and Tuba Yıldırım*

Volume 22, Issue 6, 2022

Published on: 05 August, 2021

Page: [1124 - 1138] Pages: 15

DOI: 10.2174/1871520621666210805144252

Price: $65

Abstract

Background: As a class with biological properties, such as anti-cancer, anti-bacterial, anti-HIV, and various physical effects, phosphazene derivatives constitute the most striking part of inorganic compounds. Anthraquinones, on the other hand, are a broad family of compounds with a wide variety of biological properties; the biologically active anthraquinones have been used as valuable compounds for biochemical and pharmacological research.

Objective: In this study, we aimed to investigate the effect of the anthraquinone substituted cyclotriphosphazene compounds on apoptosis and drug resistance in MCF-7 and DLD-1 cells.

Methods: In breast and colon cells, mRNA levels of multi-drug resistance genes (ABCB1, ABCC3, ABCC10, ABCC11, and ABCG2), apoptotic genes (BAX, BCL-2, p53, and PARP), heat shock (HSP27, HSP40, HSP60, HSP90α) and endoplasmic reticulum chaperone genes (GRP78, and GRP94) were determined by the qPCR method. The amount of proteins of the cell cycle, HSPs, apoptosis, and related signaling pathways were measured by the membrane array kits.

Results: Compounds 2, 3, 4, and 7 showed the most potent results on the ATP-binding cassette genes in both breast and colon cancer cells. These compounds have a remarkable effect on apoptotic, heat shock, and ER chaperone genes in cancer cells. Besides, these compounds induced protein levels of pro-apoptotic pathways, leading to apoptosis by inhibiting anti-apoptotic pathways. Also, these compounds decreased HSPs.

Conclusion: These compounds have potential properties that eliminate drug resistance, suppress heat shock and ER chaperone genes, and drag cells to apoptotic cell death and are notable for drug studies.

Keywords: ATP-binding cassette transporters, apoptosis, heat shock proteins, hydroxyanthraquinone, cyclotriphosphazenes, cancer cells

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