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

Yahya, Shaymaa M. M.; Abdelhamid, Abdou O.; Abdelhalim, Mervat M.; Elsayed, Ghada H.; Eskander, Emad F.

doi:10.1016/j.steroids.2017.08.002

Cited by 19 publications

(15 citation statements)

References 44 publications

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“…The effect of miR-34a inhibition on progesterone derivatives treated MCF-7 cells is summarized in Figure 3. in a previous work of our research group all tested progesterone derivatives (compounds 2, 3, 4, 6, 7, 8, and 9) revealed noticeable down-regulation of BCL-2 gene expression level as compared to control cells (Yahya et al, 2017). However, MCF-7 cells treated with tamoxifen showed only a non-significant reduction on BCL-2 expression in MCF-7 cells treated with compound 4 individually; however, upon synergistically inhibiting miR-34a, P53 was significantly up regulated in MCF-7 cells treated with tamoxifen, compounds 7, and 8 (Table 4).…”

Section: Resultsmentioning

confidence: 63%

“…Similarily, treating MCF-7 with miR-34a inhibitor synergistically with compounds 7 and tamoxifen resulted in reduction in CCND1 expression level while compounds 2, 4, 6, 7, 9 produced a non significant reduction in this gene expression levels (Table 3). Previously (Yahya et al, 2017), treating MCF-7 cells with compounds 3, 4, 8 individually resulted in significant reduction in CCND1 gene expression levels, meanwhile compounds 6, 7, and 9 resulted in non-significant reductions in the expression levels of CCND1 gene. Interestingly, CDC-2 gene expression was dramatically decreased in miR-34a suppressed MCF-7 cells treated with compounds 3, 7, 8, 9, in addition to a non significant reduction in cells treated with tamoxifen, compounds 2, 4, and 6 (Table 3 individually.…”

Section: Resultsmentioning

confidence: 99%

“…While, the cells in the 2 nd plate were subjected to miRNA extraction to verify successful transfection. These compounds were synthesized and subject to cytotoxicity analysis in a previous work (Yahya et al, 2017). The cells were incubated with various concentrations of the test compounds (6.25, 12.5, 25 and 50 μM) for 48 h at a cell density of 104 cells/well of 96 well plate.…”

Section: Cell Propagation Maintenance and Treatmentmentioning

confidence: 99%

“…Four parameter equation logistic curve was used (log concentration vs. % cell growth as compared to control cells). The structures of these compounds are illustrated in Figure 1 ( Yahya et al, 2017) and their IC 50 values are listed in Table 1.…”

Section: Cell Propagation Maintenance and Treatmentmentioning

confidence: 99%

“…Besides, it is a candidate for diagnostic as well as a prognostic biomarker Raptiet al, 2017;Chen et al, 2017). In a recent work (Yahya et al, 2017), our group introduced newly synthesized pyridine, thiazole, thiazolopyridine, pyrazole, and pyrazolopyridine progesterone derivatives. These compounds were prepared and tested for their anti-proliferative effects where they proved a noticeable anti-proliferative action on breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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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?

Yahya

Abdelhalim

Abdelhamid

et al. 2021

Asian Pac J Cancer Prev

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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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Section: Resultsmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Section: Cell Propagation Maintenance and Treatmentmentioning

confidence: 99%

Section: Cell Propagation Maintenance and Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Yahya

Abdelhalim

Abdelhamid

et al. 2021

Asian Pac J Cancer Prev

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New furochromone derivatives as promising in‐vitro anti‐proliferative agents toward HepG‐2 and MCF‐7 cell lines with molecular docking studies

Fawzy

Ahmed

Abo-Salem

et al. 2020

Journal of Heterocyclic Chem

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Based on the considerable features of the multicomponent reactions (MCRs) in the field of organic and medicinal chemistry, the present work was designed to synthesize a new series of imidazole, pyridine, and pyrimidine derivatives using MCRs to obtain new anti‐proliferative agent beside exploration of their interaction mechanism by molecular docking technique. MCRs of furochromone carbaldehyde 1, benzoin, and ammonium acetate afforded the corresponding 2,4,5‐trisubstituted imidazole 2. However, MCRs of 1 with benzoin, amine derivatives, and ammonium acetate yielded the corresponding 1,2,4,5‐tetrasubstituted imidazole 3a,b. In addition, pyridine 4a,b‐5a,b and pyrimidine derivatives 6a,d were synthesized via condensation of 1 with different carbonyl compounds and ammonium acetate or benzyl urea, respectively. The in‐vitro anti‐Proliferative activities of the new furochromone derivatives were screened toward MCF‐7 and HepG‐2 cancer cell lines as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5‐fluorouracil and doxorubicin using MTT assay. Compounds 5a and 5b revealed effective anti‐proliferative activity against MCF‐7 cell lines with IC 50 18 and 22 μg/mL, respectively, compared to 5‐fluorouracil (IC 50 of 13 μg/mL). However, compounds 6a‐d exhibited potent activity against HepG‐2 cancer cell lines of IC 50 ranging from 18 to 20 μg/mL compared to doxorubicin (IC 50 of 14 μg/mL). Moreover, the binding mode of the most active furochromones 5a,b and 6a‐d inside the active site of the epidermal growth factor receptor (EGFR) kinase enzyme (PDB ID: 5CAV) were studied using molecular docking technique. Compounds 6b,c showed excellent docking results compared to the known EGFR inhibitors (4ZQ).

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Recent approaches to the synthesis of thieno[2,3-b]pyridines (microreview)

Sajadikhah

Marandi

2019

Chem Heterocycl Comp

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

Cited by 19 publications

References 44 publications

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

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

New furochromone derivatives as promising in‐vitro anti‐proliferative agents toward HepG‐2 and MCF‐7 cell lines with molecular docking studies

Recent approaches to the synthesis of thieno[2,3-b]pyridines (microreview)

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