الفهرس 
Introduction and aim of the workOnly 14 pages are availabe for public view
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Abstract
Worldwide statistics show that the 3rd most common cancer is CRC after breast and lung cancers and the developed regions contain two-thirds of all CRCs found in the world. Lung cancer is one amongst the foremost common tumours, once a year over a million-individual die from this cancer. Nowadays, the most available treatments of NSCLC are ineffective and meagre, that is why it is necessary to look for new drugs that may replace or assist those presently used.
There were intensive researches and studies done on apoptosis over the last 30 years, which is established as programmed cell death. Apoptosis is a rigorous, definite and solid pathway used to kill and remove cells that are not needed or have DNA injury/damage which could not be repaired. This cellular suicide mechanism is always starting with the induction of caspases then DNases enzymes followed by degradation of proteins and DNA, then alteration of the cell membrane, which is sensed by macrophages. The execution of apoptosis comes with specific hallmark changes of cell morphology comprise of cell shrinkage, induction of distress signals, membrane blebbing, nuclear DNA breaks into fragments and stimulation of proteases which known as the caspases and displacement of phosphatidylserine are all seen and involved in this process.
Ciprofloxacin belongs to the category of 4-fluoroquinolone antibiotics that are remarkably employed in the therapeutic treatment of many bacterial infections. It can inhibit bacterial DNA gyrase enzyme, which shows antimicrobial activity. However, this drug has additionally been shown to have an effect on mammalian topoisomerase II. Shortly once it is introduced into everyday use, Ciprofloxacin showed antitumor characteristics like inducing cell cycle arrest and caspase-mediated cell death and creating double-strand cuts in DNA.
It has been reported that the insertion of a substituent on N-4-piperazinyl moiety of ciprofloxacin has improved the physicochemical properties of the parent quinolone with significant therapeutic differences as a potential antitumor candidate not only antibacterial drug. Our goal in this study is to investigate the effect of a new 7-(4-(N-substituted carbamoyl methyl) piperazin-1 yl) derivative of ciprofloxacin as an anticancer candidate.
Therefore, the aim of this study to investigate the anti-proliferative and apoptotic effects of this ciprofloxacin new derivative on the colorectal cancer cell line (HCT 116) and non-small lung carcinoma cell line (A549), and examine its ability to arrest cell cycle and cause apoptosis via p53/bax/bcl2 dependent pathway and p53 inhibition of p21 dependent pathway as well.
Our results revealed that the new derivative inhibited proliferation of HCT116 and A549 cancer cells in a dose-dependent manner with IC50 of 66.68 & 50.8 µg/ml, respectively. The exposure of HCT116 and A549 cancer cells to our new compound induced apoptosis and produced cell cycle arrest at G2/M phase.
In HCT 116 and A549 cell lines, the expression of pro-apoptotic factors, p53 and bax, showed significant elevation following the treatment with our compound when compared to the control untreated cells, while the expression of anti-apoptotic factors, bcl2 and p21, showed significant declining in the treated cells when compared to the untreated cells.
In conclusion, the present study investigated the antiproliferative, apoptotic and anticancer activity of the 7-(4-(N-substituted carbamoyl methyl) piperazin-1 yl) derivative of ciprofloxacin. It induced a dose-dependent inhibition in the survival of human HCT116 and A549 cancer cells. This new ciprofloxacin derivative initiates cell cycle arrest at G2/M phase and induces apoptosis via P53/Bax/bcl2 pathway and p53 dependent repression of p21 signaling pathway. The outcomes of the present study may contribute toward a promising perspective on the therapeutic characteristics of this new synthesized ciprofloxacin derivative for the treatment of colorectal cancer and non-small lung carcinoma. However, much work is required to obtain adequate knowledge regarding the anticancer activity of this new compound.