Abstract
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.
Highlights
Breast cancer was found to account for 22% of newly discovered cancer cases each year in women
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 revealed noticeable down-regulation of BCL-2 gene expression level as compared to control cells (Yahya et al, 2017)
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)
Summary
Breast cancer was found to account for 22% of newly discovered cancer cases each year in women. 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. 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”. 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. 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. 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. MiR-34a inhibitor could be used safely as a tool to tackle drug resistance in breast cancer cells
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