title: Evaluation of heterocyclic steroids and curcumin derivatives as anti-breast cancer agents: Studying the effect on apoptosis in MCF-7 breast cancer cells.
abstract: 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=18μM) 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.
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt (ID:60014618). Electronic address: gamalae@hotmail.com.
authors.forename: Gamal A
authors.initials: GA
authors.lastname: Elmegeed
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt (ID:60014618).
authors.forename: Shaymaa M M
authors.initials: SM
authors.lastname: Yahya
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt (ID:60014618).
authors.forename: Mervat M
authors.initials: MM
authors.lastname: Abd-Elhalim
authors.affiliation: Chemistry Department, Faculty of Science, Cairo University, Cairo, Egypt; Biochemistry Speciality, Faculty of Science, Cairo University, Cairo, Egypt.
authors.forename: Mervat S
authors.initials: MS
authors.lastname: Mohamed
authors.affiliation: Chemistry Department, Faculty of Science, Cairo University, Cairo, Egypt.
authors.forename: Rafat M
authors.initials: RM
authors.lastname: Mohareb
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt (ID:60014618).
authors.forename: Ghada H
authors.initials: GH
authors.lastname: Elsayed
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism*; D016203:CDC2 Protein Kinase; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D019938:Cyclin D1 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013260:Steroids, Heterocyclic / Q000737:chemistry / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D013260:Steroids, Heterocyclic; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D003474:Curcumin
keywords: Apoptotic genes; Breast cancer; Cytotoxicity; Heterocycles; Steroids