الرئيسية / علماء مصر (الطيور المهاجرة) / Hamada H. H. Mohammed , Amer Ali Abd El-Hafeez , Samar H. Abbas , El-Shaimaa M. N. Abdelhafez, Gamal El-Din A. Abuo-Rahma (AEA-Scholars)

Hamada H. H. Mohammed , Amer Ali Abd El-Hafeez , Samar H. Abbas , El-Shaimaa M. N. Abdelhafez, Gamal El-Din A. Abuo-Rahma (AEA-Scholars)

Hamada H. H. Mohammed , Amer Ali Abd El-Hafeez , Samar H. Abbas , El-Shaimaa M. N. Abdelhafez, Gamal El-Din A. Abuo-Rahma 

Association of Egyptian-American Scholars

Background:

Cancer is considered one of the most important causes of death globally. The clinical use of chemotherapeutic agents in treatment of cancer is commonly associated with severe side effects and lack of selectivity. On the other hand, considerable attention has been paid to fluoroquinolones as antiproliferative agents via inhibition of DNA Topoisomerase II. Moreover; ciprofloxacin is a fluoroquinolone that inhibits topoisomerase II. Moreover ciprofloxacin is a fluoroquinolone that inhibits topoisomerase II. In eukaryotic, including mammalian cells. It is worth to mention that a concentration exceeding 80µg/mL ciprofloxacin was found to induce apoptosis, while at concentration of 25µg/mL it inhibits the proliferation of Jukat cells without cell death. Ciprofloxacin is also known for its anticancer properties by inducing G2 cell cycle arrest and apoptosis of different cancer cells. Therefore, ciprofloxacin can be used as adjuvant therapy for certain cancers.

Purpose: To provide new more selective anticancer agents with fewer side effects.

Results:

New N-4-piperazinyl derivatives of ciprofloxacin 2a—g were prepared and tested for their cytotoxic activity. The primary in vitro one dose anticancer assay experienced promising cytotoxic activity against different cancer cell lines especially non-small cell lung cancer. Independently compounds 2b, 2d, 2f and 2g showed anticancer activity against human non-

small cell lung cancer A549 cells (IC50 = 14.8, 24.8, 23.6 and 20.7 µM, respectively) compared to the parent ciprofloxacin (IC50 >100 µM) and doxorubicin as a positive control (IC50 = 1 µM). The flow cytometric analysis for 2b showed dose dependent G2/M arrest in A549 cells. Also, 2b increased the expression of p53 and p21 and decreased the expression of cyclin B1 and Cdc2 proteins in A549 cells without any effect on the same proteins expression in WI-38 cells. Specific inhibition of p53 by pifithrin-a reversed the G2/M phase arrest induced by the 2b compound, suggesting contribution of p53 to increase. Taken together, 2b induced G2/M phase arrest via p53/p21 dependent pathway. The results indicate that 2b can be used as a lead compound for further development of new derivatives against non-small cell lung cancer.

Conclusion:

Studying the mechanism of action of compound 2b was accomplished using flow cytometric analysis. Compound 2b showed dose dependent G2/M cell cycle arrest in A549 cell line. Also, 2b increased the expression of p53 and p21 and decreased the expression of cyclin B1 and Cdc2 proteins in A549 cells without any effect on WI-38 cells. Specific inhibition of p53 by pifithrin-a reduced the percentage of cells accumulated in G2/M phase, suggesting contribution of p53 to G2/M phase arrest in A549 cells. Therefore, compound 2b is considered a promising candidate that requires further investigation and optimization for treatment of non-small cell lung cancer.

This article was published in 3alamaltanmya

sponsored by Future Builders International Academy

Led by Dr.Maha Fouad

e5f2ef68-75e1-4678-9ffc-3479da505483

شاهد أيضاً

(Elsayed Elzayat (AEA-Scholars

Elsayed Elzayat Association of Egyptian-American Scholars Abstract: We assume that the way we “see” things …

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