Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for... more Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for the treatment of numerous forms of cancer, but it has marked adverse effects, namely nephrotoxicity, hepatotoxicity, ototoxicity, neurotoxicity, diarrhoea etc. CDDP-induced emesis and diarrhoea are also noticeable toxicities that may be due to intestinal injury. Zingerone; a phenolic alkanone, one of the active components of ginger, possesses multiple biological activities, such as antioxidant and antiinflammatory properties. In the present study, we investigated the protective effect of zingerone against CDDP-induced jejunal toxicity. Animals were divided into five groups I-IV (n=6). Group II, III and IV received single intraperitoneal administration of CDDP at 7.5 mg/kg body weight on day 14. Animals of group II and III received oral treatment of zingerone at doses of 25 and 50 mg/kg body weight respectively for 14 consecutive days. While groups I was given distilled water 5 ml/kg body weight for 14 days. All the animals were killed after 24 h of CDDP injection. Zingerone ameliorated CDDP-induced lipid peroxidation, increase in xanthine oxidase activity, glutathione depletion, decrease in antioxidant and phase-II detoxifying enzyme activities. Zingerone attenuated CDDP-induced nuclear factor (NF-κB) activation, enhanced levels of TNF-α and Nitrite. The results showed that zingerone had not only the antioxidant effect by suppression of ROS, but also antiinflammatory effects by suppression of NF-κB activation. In addition, zingerone treatment suppressed gene activation of pro-inflammatory cytokine, TNF-α, which was upregulated with CDDP administration through NF-κB activation. These experiments strongly indicate that zingerone treatment exercises a protective efficacy by suppressing both oxidative stress and inflammation through the modulation of key pro-inflammatory cytokine and transcription factors.
Cell cycle dysregulation is a characteristic hallmark of malignancies, which results in uncontrol... more Cell cycle dysregulation is a characteristic hallmark of malignancies, which results in uncontrolled cell proliferation and eventual tumor formation. Cyclin-dependent kinase 1 (CDK1) is a member of the family of cell cycle regulatory proteins involved in cell cycle maintenance. Given that overexpression of CDK1 has been associated with cancer, CDK1 inhibitors may restore equilibrium to the skewed cell cycle system and operate as an effective therapeutic drug. This study aimed to identify and classify inhibitors having a higher affinity for CDK1 and also evaluate the expression pattern and prognostic relevance of CDK1 in a wide range of cancers. We investigated therapeutic molecules structurally similar to dinaciclib for their ability to inhibit CDK1 selectively. To assess the therapeutic potential of screened Dinaciclib analogs, we used drug likeliness analysis, molecular docking, and simulation analysis. CDK1 was found to be highly upregulated across several malignancies and is associated with poor overall and relapse-free survival. Molecular docking and dynamics evaluation identified two novel dinaciclib analogs as potent CDK1 inhibitors with high binding affinity and stability compared to dinaciclib. The results indicate that increased CDK1 expression is associated with decreased OS and RFS. Additionally, dinaciclib analogs are prospective replacements for dinaciclib since they exhibit increased binding affinity, consistent with MDS findings, and have acceptable ADMET qualities. The discovery of new compounds may pave the road for their future application in cancer prevention through basic, preclinical, and clinical research.
and Springer Science+Business Media Dordrecht. This e-offprint is for personal use only and shall... more and Springer Science+Business Media Dordrecht. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".
Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for... more Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for the treatment of numerous forms of cancer, but it has marked adverse effects, namely nephrotoxicity, hepatotoxicity, ototoxicity, neurotoxicity, diarrhoea etc. CDDP-induced emesis and diarrhoea are also noticeable toxicities that may be due to intestinal injury. Zingerone; a phenolic alkanone, one of the active components of ginger, possesses multiple biological activities, such as antioxidant and antiinflammatory properties. In the present study, we investigated the protective effect of zingerone against CDDP-induced jejunal toxicity. Animals were divided into five groups I-IV (n=6). Group II, III and IV received single intraperitoneal administration of CDDP at 7.5 mg/kg body weight on day 14. Animals of group II and III received oral treatment of zingerone at doses of 25 and 50 mg/kg body weight respectively for 14 consecutive days. While groups I was given distilled water 5 ml/kg body weight for 14 days. All the animals were killed after 24 h of CDDP injection. Zingerone ameliorated CDDP-induced lipid peroxidation, increase in xanthine oxidase activity, glutathione depletion, decrease in antioxidant and phase-II detoxifying enzyme activities. Zingerone attenuated CDDP-induced nuclear factor (NF-κB) activation, enhanced levels of TNF-α and Nitrite. The results showed that zingerone had not only the antioxidant effect by suppression of ROS, but also antiinflammatory effects by suppression of NF-κB activation. In addition, zingerone treatment suppressed gene activation of pro-inflammatory cytokine, TNF-α, which was upregulated with CDDP administration through NF-κB activation. These experiments strongly indicate that zingerone treatment exercises a protective efficacy by suppressing both oxidative stress and inflammation through the modulation of key pro-inflammatory cytokine and transcription factors.
Cell cycle dysregulation is a characteristic hallmark of malignancies, which results in uncontrol... more Cell cycle dysregulation is a characteristic hallmark of malignancies, which results in uncontrolled cell proliferation and eventual tumor formation. Cyclin-dependent kinase 1 (CDK1) is a member of the family of cell cycle regulatory proteins involved in cell cycle maintenance. Given that overexpression of CDK1 has been associated with cancer, CDK1 inhibitors may restore equilibrium to the skewed cell cycle system and operate as an effective therapeutic drug. This study aimed to identify and classify inhibitors having a higher affinity for CDK1 and also evaluate the expression pattern and prognostic relevance of CDK1 in a wide range of cancers. We investigated therapeutic molecules structurally similar to dinaciclib for their ability to inhibit CDK1 selectively. To assess the therapeutic potential of screened Dinaciclib analogs, we used drug likeliness analysis, molecular docking, and simulation analysis. CDK1 was found to be highly upregulated across several malignancies and is associated with poor overall and relapse-free survival. Molecular docking and dynamics evaluation identified two novel dinaciclib analogs as potent CDK1 inhibitors with high binding affinity and stability compared to dinaciclib. The results indicate that increased CDK1 expression is associated with decreased OS and RFS. Additionally, dinaciclib analogs are prospective replacements for dinaciclib since they exhibit increased binding affinity, consistent with MDS findings, and have acceptable ADMET qualities. The discovery of new compounds may pave the road for their future application in cancer prevention through basic, preclinical, and clinical research.
and Springer Science+Business Media Dordrecht. This e-offprint is for personal use only and shall... more and Springer Science+Business Media Dordrecht. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".
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