Evaluation of heterocyclic steroids and curcumin derivatives as anti breast cancer agents: Studying the effect on apoptosis in MCF-7 breast cancer cells

被引：36

作者：

Elmegeed, Gamal A. ^{[1
]}

Yahya, Shaymaa M. M. ^{[1
]}

Abd-Elhalim, Mervat M. ^{[1
]}

Mohamed, Mervat S. ^{[2
,3
]}

Mohareb, Rafat M. ^{[2
]}

Elsayed, Ghada H. ^{[1
]}

机构：

[1] Natl Res Ctr, Hormones Dept, Giza 12622, Egypt

[2] Cairo Univ, Dept Chem, Fac Sci, Cairo, Egypt

[3] Cairo Univ, Biochem Special, Fac Sci, Cairo, Egypt

来源：

STEROIDS | 2016年 / 115卷

关键词：

Apoptotic genes; Breast cancer; Cytotoxicity; Heterocycles; Steroids; GROWTH-INHIBITION; CYCLIN D1; SURVIVIN; DEATH; P53; MEDIATOR;

D O I：

10.1016/j.steroids.2016.08.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Anticancer agents consisting of hybrid molecules are used to improve effectiveness and diminish drug resistance. The current study aimed to introduce newly synthesized hetero-steroids of promising anticancer effects. Besides, the pro-apoptotic effects of new compounds were investigated extensively. Several pyrimidino-, triazolopyrimidino-, pyridazino-, and curcumin-steroid derivatives were synthesized, elucidated and confirmed using the spectral and analytical data. The synthesized hetero-steroids, compounds 9, 10, 11, 12, 13, 14, 15, 18, 20, 21, 22 and 24, were tested for their cytotoxic effects versus human breast cancer cells (MCF-7) using neutral red supravital dye uptake assay. Compound 24 (IC50 = 18 mu M) showed more inhibitory influence on MCF-7 growth. Using QRT-PCR (Quantitative real time-polymerase chain reaction), CCND1, Survivin, BCL-2, CDC2, P21 and P53, genes expression levels were investigated. The study results disclose that compounds 4, 7, 18, 24 knocked down the expression levels of CCND1, Survivin, BCL-2 and CDC2. However, P21 and P53 were up-regulated by compounds 21, 22. This study introduced promising pro-apoptotic anticancer agents acting through the modulation of key regulators of apoptosis and cell cycle genes. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：80 / 89

页数：10

共 46 条

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