Publications by authors named "Ghada H Elsayed"

7 Publications

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Could miR-34a Inhibition be Used as a Tool to Overcome Drug Resistance in MCF-7 Cells Treated with Synthesized Steroidal Heterocycles?

Asian Pac J Cancer Prev 2021 Mar 1;22(3):819-826. Epub 2021 Mar 1.

Department of Hormones, Medical Research Division, National Research Centre, Dokki, Cairo, Egypt.

Background: Progesterone derivatives have explored an improved effect on human cancer cells through combination of the explored heterocycles with progesterone moiety.miRNAs have an important role in moderating cancer cell survival, proliferation and drug resistance. The current study tested the hypothesis "whether miR-34a inhibitor has a negative impact on apoptosis and angiogenesis in MCF-7 cells treated with newly synthesized progesterone derivatives".

Methods: MCF-7 cells were treated with progesterone derivatives individually and in combination with miR-34a inhibitor. miR-34a expression levels were measured in MCF-7 cells treated with progesterone derivatives using QRT-PCR. MCF-7 cells treated with progesterone derivatives individually showed increased miR-34a expression levels. miR-34a deficient cells were treated with the newly synthesized progesterone derivatives, after that, apoptotic and angiogenic gene expression levels were determined using QRT-PCR. The studied genes were as follows: apoptotic (Bcl-2, survivin, CCND1, CDC2, P53 and P21) and angiogenic (VEGF, Hif-1α, MMP-2, Ang-1, Ang-2, and FGF-1).

Results: The results showed that miR-34a deficient MCF-7 cells treated with the newly progesterone derivatives still have promising effects on apoptotic and angiogenic genes. Besides, results revealed that miRNA-34a deficient MCF-7 cells exhibited improved effect of tested compounds in some apoptotic and angiogenic genes such as CDC-2, MMP-2.

Conclusion: These results revealed that miR-34a inhibitor did not have remarkable negative effect on apoptosis and angiogenesis. On contrary, it showed an improved effect on some genes. And consequently, miR-34a inhibitor could be used safely as a tool to tackle drug resistance in breast cancer cells.
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http://dx.doi.org/10.31557/APJCP.2021.22.3.819DOI Listing
March 2021

Synthesis and cytotoxic evaluation of novel hybrid estrane heterocycles as chemotherapeutic anti-cancer agents.

Steroids 2021 Feb 27;169:108813. Epub 2021 Feb 27.

Hormones Department, National Research Centre, 12622 Dokki, Giza, Egypt.

New synthesized hybrid steroidal heterocyclic compounds have received a lot of attention in view of their biological activities as anticancer agents. In this study, a novel class of hybrid estrane heterocyclic compounds were synthesized and evaluated by analytical and spectral data which proved the validity of these derivatives. The cytotoxicity of synthesized compounds 2a, 2b, 2c, 3b, 8, 10a, 10b, 13, 14, 16a and 19 against three human cell lines: breast cancer cells (MCF-7), prostate cancer cells (PC3), and liver cancer cells (HepG2) has been tested using MTT assay. Compounds 10a, 10b, 2c, and 14 revealed more inhibitory influence on MCF7, PC3 and HepG2 growth than the reference drug doxorubicin (Dox) after 24 h incubation. Noteworthy, the tested compounds 10a, 10b, 2c, and 14 exhibited the most pronounced effect in this respect. The results were confirmed by morphology study.
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http://dx.doi.org/10.1016/j.steroids.2021.108813DOI Listing
February 2021

The Effect of Newly Synthesized Heterosteroids on miRNA34a, 98, and 214 Expression Levels in MCF-7 Breast Cancer Cells.

Indian J Clin Biochem 2018 Jul 26;33(3):328-333. Epub 2017 Jul 26.

1Hormones Department, National Research Centre, Dokki, Giza, 12622 Egypt.

Hybrid anticancer drugs have emerged as great therapeutic options that can effectively overcome most obstacles facing conventional anticancer drugs. miRNAs are considered as class of non-coding RNAs that can negatively regulate protein coding gene expression. miRNA expression is commonly altered in cancer cells. The current work aimed to test the effect of new pro-apoptotic heterosteroids on some drug resistance related miRNAs expression levels (miRNA34a, 98, and 214) in MCF-7 breast cancer cells. After cell treatment with these compounds , , , , , , and , miRNAs were extracted and subjected to reverse transcription and subsequent PCR amplification using Real Time-PCR technique. The expression levels of miR-34a, miR-98 and miR-214 were quantitatively determined. The study revealed that the expression levels of miR-34a, miR-98 and miR-214 were up-regulated upon treatment with tamoxifen, which was used as a positive control drug, as compared to control cells,. Strikingly, the levels of miR-34a, miR-98 and miR-214 expression were significantly down-regulated when treated with most of the new heterosteroids as compared to control cells. These results could indicate the promising effects of these new heterosteroids on reducing drug resistance as compared to tamoxifen drug. As well established, cells develop drug resistance to tamoxifen.
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http://dx.doi.org/10.1007/s12291-017-0681-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052734PMC
July 2018

The effect of newly synthesized progesterone derivatives on apoptotic and angiogenic pathway in MCF-7 breast cancer cells.

Steroids 2017 10 8;126:15-23. Epub 2017 Aug 8.

Hormones Department, National Research Centre, Dokki, Giza, Egypt.

Due to its high potency and selectivity, anticancer agents consisting of combined molecules have gained great interests. The current study introduces newly synthesized progesterone derivatives of promising anticancer effect. Moreover, the pro-apoptotic and anti-angiogenic effects of these compounds were studied extensively. Several thiazole, pyridine, pyrazole, thiazolopyridine and pyrazolopyridine progesterone derivatives were synthesized. The structure of the novel progesterone derivatives was elucidated and confirmed using the analytical and spectral data. This novel derivatives were tested for their cytotoxic effect against human breast cancer cells (MCF-7) using neutral red uptake assay. Tested compounds showed anticancer activity against MCF-7 cancer cell line in the descending order of 7>2>3>8>6>9>4. The expression levels of Bcl-2, survivin, CCND1, CDC2, P53 and P21, VEGF, Hif-1α, MMP-2, MMP-9, Ang-1, Ang-2, and FGF-1 genes were investigated using QRT-PCR (Quantitative real time-polymerase chain reaction). The study clarified that compounds 2, 3, 4, 6, 7, 8 and 9 showed significant pro-apoptotic effect through the down regulation of Bcl-2., besides, survivin and CCND1 expression levels were down regulated by compounds 3, 4, 6, 7, 8, 9. However, Compound 4 may exert this pro-apoptotic effect through the up-regulation of P53 gene expression. On the other hand, the anti-angiogenic effect of these newly synthesized derivatives was due to their down regulation of VEGF, Ang-2, MMP-9 and FGF-1; and the up-regulation of HIF-1α and ang-1. This study recommended promising pro-apoptotic and anti-angiogenic anticancer agents acting through the regulation of key regulators of apoptosis, cell cycle genes, and pro-angiogenic genes.
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http://dx.doi.org/10.1016/j.steroids.2017.08.002DOI Listing
October 2017

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

Steroids 2016 11 21;115:80-89. Epub 2016 Aug 21.

Hormones Department, National Research Centre, Dokki, Giza, Egypt (ID:60014618).

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.
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http://dx.doi.org/10.1016/j.steroids.2016.08.014DOI Listing
November 2016

A summary for molecular regulations of miRNAs in breast cancer.

Clin Biochem 2015 Apr 23;48(6):388-96. Epub 2014 Dec 23.

Hormones Department, Medical Division, National Research Centre, Dokki, Cairo, Egypt. Electronic address:

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. MicroRNAs (miRNAs) are naturally-occurring, non-coding small RNA molecules that can modulate protein coding-genes, which makes it contributing to nearly all the physiological and pathological processes. Progression of breast cancer and resistance to endocrine therapies have been attributed to the possibility of hormone-responsive miRNAs involved in the regulation of certain signaling pathways.

Methodology: This review introduces better understanding of miRNAs to provide promising advances for treatment. miRNAs have multiple targets, and they were found to regulate different signaling pathways; consequently it is important to characterize their mechanisms of action and their cellular targets in order to introduce miRNAs as novel and promising therapies.

Results: This review summarizes the molecular mechanisms of miRNAs in TGF-beta signaling, apoptosis, metastasis, cell cycle, ER-signaling, and drug resistance.

Conclusion: Finally, miRNAs will be introduced as promising molecules to be used in the fight against breast cancer and its developed drug resistance.
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http://dx.doi.org/10.1016/j.clinbiochem.2014.12.013DOI Listing
April 2015

Cytotoxicity and gene expression profiles of novel synthesized steroid derivatives as chemotherapeutic anti-breast cancer agents.

Bioorg Med Chem 2011 Nov 22;19(22):6860-72. Epub 2011 Sep 22.

Hormones Department, National Research Centre, Dokki, Giza, Egypt.

Anti-cancer agents which combine two biologically active compounds in one such as steroidal heterocyclic derivatives attain both hormone and cytotoxic effects on cancer cells. The aim of the present study is to synthesize and evaluate new potential chemotherapeutic anti-breast cancer agents. Several pyridazino-, pyrimido-, quinazolo-, oxirano- and thiazolo-steroid derivatives were synthesized. The structure of the novel steroid derivatives was confirmed using the analytical and spectral data. The most structurally promising of the novel synthesized steroid derivatives, compounds 8, 12, 17, 20, 22c, 24c, 30a and 30b, were investigated individually as anti-breast cancer agents against human breast cancer cells (MCF-7) using sulforhodamine B (SRB) assay. The tested compounds 17, 20, 22c and 8 showed potent broad spectrum cytotoxic activity in vitro after 48 h incubation. Compound 17 (IC(50)=2.5 μM) exhibited more inhibitory influence on MCF-7 growth than the reference drug doxorubicin (Dox) (IC(50)=4.5 μM) after 48 h incubation. Also, the present study showed that all the tested steroid derivatives exhibited significant depletion with various intensities in gene expression of breast cancer related genes (VEGF, CYP19 and hAP-2γ). Noteworthy, compounds 17, 20 and 22c showed the most pronounced effect in this respect.
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http://dx.doi.org/10.1016/j.bmc.2011.09.033DOI Listing
November 2011