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Abstract
In our era there has been several anti-cancer drugs which have undergone both experimental and clinical trials; however, due to their poor solubilities, numerous side effects, insufficient bioavailability and poor compliance, many have resulted into poor outcomes. Therefore, our aim was to investigate the effects of novel hydrophilic taxanes analogues CQMU-0517 and CQMU-0519 on growth of A549 lung, SKVO3 ovary and MCF7 breast carcinoma cell lines. Different concentrations of original paclitaxel, CQMU-0517, original docetaxel and CQMU-0519 were utilized on three cell lines, where cell growth was assessed using cell culture kit-8 and flow cytometry analysis. The results unveiled that CQMU-0517 and CQMU-0519 suppressed cell growth in the three particular cell lines, cell cycle arrest being evident in the G2/M phase. Hence, the results showed that these new taxane analogues have potential and warrant future clinical trials.
Highlights
During the past decades, innumerable experimental studies on taxol, taxotere and their homologs have been carried out all over the world so as to try to carve a pathway for clinical oncological trials
10, 100 and 1000nM of original Paclitaxel and CQMU0517were used, at 1000 nM after 24 hours, CQMU-0517 displayed more cell growth inhibitory effects in A549 lung, SKVO3 ovarian and MCF7 breast cell lines with IC50 values of 7.36 μg/ml, 10.96 μg/ml and 10.73 μg/ml respectively calculated from concentration dependent curves
0517 showed an increase in inhibition of cell proliferation compared with original paclitaxel (*P < 0.05). b) A549, SKVO3 f and MCF7 cells exposed to 50nM of CQMU-0519 showed an increase in inhibition of cell proliferation compared with original
Summary
Innumerable experimental studies on taxol, taxotere and their homologs have been carried out all over the world so as to try to carve a pathway for clinical oncological trials. Their mechanism of actions, pharmacokinetics, activation of signal transduction pathways, side effects are few of the characteristics that have been delineated through experimental trials. Taxanes have been amongst the most solicited chemotherapeutic drugs of our era, grouping mainly Paclitaxel (Taxol®) and Docetaxel (Taxotere®) which forms part of the second generation of Taxanes called as mitotic poisons or mitotic inhibitors undergoing profound and meticulous laboratory and clinical investigations. Paclitaxel and docetaxel are both derived from renewable natural sources such as Taxus brevifolia (bark of Pacific yew/Western yew) (Wani et al, 1971), and Taxus baccata (needles of European Yew) (Bissery et al, 1991) and despite being slightly more soluble in water than Taxol® (Hennenfent and Govindan, 2006), both need to be solubilised in polysorbate 80 for its commercial formulation, bearing a lot of side effects
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