A quinoline derivative exerts antineoplastic efficacy against solid tumour by inducing apoptosis and anti-angiogenesis both in vitro and in vivo.
| Title: | A quinoline derivative exerts antineoplastic efficacy against solid tumour by inducing apoptosis and anti-angiogenesis both in vitro and in vivo. |
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| Authors: | Kumar C P; Department of Biochemistry, Jnana Sahyadri, Kuvempu University, Shankaraghatta, 577451, Shimoga, Karnataka, India.; Banumathi; Molecular Biomedicine Laboratory, Post Graduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, 577 203, Karnataka, India.; Satyanarayan ND; Department of Pharmaceutical Chemistry, Post-Graduate Centre, Kuvempu University, Kadur, 577548, Chikmagalur Dist, Karnataka, India.; Prasad SR; Department of Pharmaceutical Chemistry, Post-Graduate Centre, Kuvempu University, Kadur, 577548, Chikmagalur Dist, Karnataka, India.; Achur RN; Department of Biochemistry, Jnana Sahyadri, Kuvempu University, Shankaraghatta, 577451, Shimoga, Karnataka, India. rajachur@gmail.com.; INTI International University, Nilai, Malaysia. rajachur@gmail.com.; Prabhakar BT; Molecular Biomedicine Laboratory, Post Graduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, 577 203, Karnataka, India. pbtssc@gmail.com. |
| Source: | Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2025 Jul; Vol. 398 (7), pp. 9161-9176. Date of Electronic Publication: 2025 Feb 06. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0326264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1912 (Electronic) Linking ISSN: 00281298 NLM ISO Abbreviation: Naunyn Schmiedebergs Arch Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Berlin, New York, Springer Verlag. |
| MeSH Terms: | Apoptosis*/drug effects ; Quinolines*/pharmacology ; Quinolines*/therapeutic use ; Antineoplastic Agents*/pharmacology ; Antineoplastic Agents*/therapeutic use ; Angiogenesis Inhibitors*/pharmacology ; Angiogenesis Inhibitors*/therapeutic use ; Carcinoma, Ehrlich Tumor*/drug therapy ; Carcinoma, Ehrlich Tumor*/pathology ; Neovascularization, Pathologic*/drug therapy ; Lung Neoplasms*/drug therapy ; Lung Neoplasms*/pathology; Cell Proliferation/drug effects ; Animals ; Humans ; Mice ; Cell Line, Tumor ; A549 Cells ; Mice, Inbred BALB C |
| 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.; (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
| Competing Interests: | Declarations. Ethical approval: The animals used throughout the study were maintained as per CPCSEA guidelines with clearance from the animal ethical committee [Ref No. KSHEMA/IAEC/01/2020 Date: 04.06.2022]. No human samples were used in this study. Competing interests: The authors declare no competing interests. |
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| Grant Information: | 776 VGST KFIST-Level 1 |
| Contributed Indexing: | Keywords: Angiogenesis; Apoptosis and anticancer; Cancer; Quinoline |
| Substance Nomenclature: | 0 (Quinolines); 0 (Antineoplastic Agents); 0 (Angiogenesis Inhibitors) |
| Entry Date(s): | Date Created: 20250206 Date Completed: 20250717 Latest Revision: 20250717 |
| Update Code: | 20260130 |
| DOI: | 10.1007/s00210-025-03830-8 |
| PMID: | 39912901 |
| Database: | MEDLINE |
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