Al-Hayali, Mohammed Zuhair and Nge, Choy-Eng and Lim, Kuan Hon and Collins, Hilary M. and Kam, Toh Seok and Bradshaw, Tracey D. (2024) Conofolidine: A Natural Plant Alkaloid That Causes Apoptosis and Senescence in Cancer Cells. Molecules, 29 (11). p. 2654. ISSN 1420-3049, DOI https://doi.org/10.3390/molecules29112654.
Full text not available from this repository.Abstract
Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel Aspidosperma-Aspidosperma bisindole alkaloid isolated from the Malayan plant Tabernaemontana corymbosa. Herein, we report conofolidine's broad-spectrum anticancer activity together with that of three other bisindoles-conophylline, leucophyllidine, and bipleiophylline-against human-derived breast, colorectal, pancreatic, and lung carcinoma cell lines. Remarkably, conofolidine was able to induce apoptosis (e.g., in MDA-MB-468 breast) or senescence (e.g., in HT-29 colorectal) in cancer cells. Annexin V-FITC/PI, caspase activation, and PARP cleavage confirmed the former while positive beta-gal staining corroborated the latter. Cell cycle perturbations were evident, comprising S-phase depletion, accompanied by downregulated CDK2, and cyclins (A2, D1) with p21 upregulation. Confocal imaging of HCT-116 cells revealed an induction of aberrant mitotic phenotypes-membrane blebbing, DNA-fragmentation with occasional multi-nucleation. DNA integrity assessment in HCT-116, MDA-MB-468, MIAPaCa-2, and HT-29 cells showed increased fluorescent gamma-H2AX during the G1 cell cycle phase; gamma-H2AX foci were validated in HCT-116 and MDA-MB-468 cells by confocal microscopy. Conofolidine increased oxidative stress, preceding apoptosis- and senescence-induction in most carcinoma cell lines as seen by enhanced ROS levels accompanied by increased NQO1 expression. Collectively, we present conofolidine as a putative potent anticancer agent capable of inducing heterogeneous modes of cancerous cell death in vitro, encouraging further preclinical evaluations of this natural product.
| Item Type: | Article |
|---|---|
| Funders: | Higher Committee of Education Development in Iraq |
| Uncontrolled Keywords: | conofolidine; bisindole alkaloids; carcinoma cell lines; cytotoxicity; apoptosis; senescence; ROS generation; gamma-H2AX |
| Subjects: | Q Science > QD Chemistry R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 20 Sep 2024 02:42 |
| Last Modified: | 20 Sep 2024 02:42 |
| URI: | http://eprints.um.edu.my/id/eprint/45162 |
Actions (login required)
 |
View Item |
