A quinoline derivative exerts antineoplastic efficacy against solid tumour by inducing apoptosis and anti-angiogenesis both in vitro and in vivo.

Abstract

Cancer is a heterogeneous and multicomplex disease with the highest morbidity and mortality rate. The targeting of tumour progression with drugs is a very well-established treatment strategy. Despite these, due to the failure of commonly used drugs in combating cancer, new drugs need to be screened and established for better therapeutic approach. With this rationale, the current investigation was aimed to develop quinoline compound (QC) derivatives as anti-tumour molecules. In this extended study, a series of QC analogues were subjected to anti proliferative assays through cell-based screening and evaluated its mechanism of action through apoptotic and anti-angiogenic assays. The change in cell behaviour was assessed through gene expression analysis using qRT-PCR and immunoblot analysis. Further, in vivo solid tumour model was developed and the anti-tumour potential of QC-4 was verified with gene expression studies. The results suggested that QC-4 exhibited significant cytotoxic effect, particularly against human lung adenocarcinoma cell lines and murine Ehrlich Ascites Carcinoma cells. The QC-4 induced condensation, nuclear damage and changes in membrane integrity resulted in apoptosis and neovascularisation inhibition. The modulation of apoptotic and angiogenic genes such as BAX, BAD, p53 and MMP-2 and 9 further supported the molecular cause of cytotoxicity induced by QC-4. The regression of in vivo solid tumour with extended survivability warranted the in vitro results and the gene expression patterns were additionally supportive. Overall, the QC-4 analogue exhibits the anti-neoplastic with a multi-target approach, reserving its capacity to be developed into a new class of the anticancer molecules.