Version 1
: Received: 5 January 2024 / Approved: 8 January 2024 / Online: 8 January 2024 (09:17:51 CET)
How to cite:
Al-Hayali, M.Z.; Nge, C.; Lim, K.H.; Collins, H.M.; Kam, T.S.; Bradshaw, T.D. Conofolidine, a Natural Plant Alkaloid Causes Apoptosis and Senescence in Cancer Cells. Preprints2024, 2024010602. https://doi.org/10.20944/preprints202401.0602.v1
Al-Hayali, M.Z.; Nge, C.; Lim, K.H.; Collins, H.M.; Kam, T.S.; Bradshaw, T.D. Conofolidine, a Natural Plant Alkaloid Causes Apoptosis and Senescence in Cancer Cells. Preprints 2024, 2024010602. https://doi.org/10.20944/preprints202401.0602.v1
Al-Hayali, M.Z.; Nge, C.; Lim, K.H.; Collins, H.M.; Kam, T.S.; Bradshaw, T.D. Conofolidine, a Natural Plant Alkaloid Causes Apoptosis and Senescence in Cancer Cells. Preprints2024, 2024010602. https://doi.org/10.20944/preprints202401.0602.v1
APA Style
Al-Hayali, M.Z., Nge, C., Lim, K.H., Collins, H.M., Kam, T.S., & Bradshaw, T.D. (2024). Conofolidine, a Natural Plant Alkaloid Causes Apoptosis and Senescence in Cancer Cells. Preprints. https://doi.org/10.20944/preprints202401.0602.v1
Chicago/Turabian Style
Al-Hayali, M.Z., Toh Seok Kam and Tracey Dawn Bradshaw. 2024 "Conofolidine, a Natural Plant Alkaloid Causes Apoptosis and Senescence in Cancer Cells" Preprints. https://doi.org/10.20944/preprints202401.0602.v1
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 anticancer activity together with that of three other bisindoles - conophylline, leucophyllidine and bipleiophylline against human-derived carcinoma cell lines. Remarkably, conofolidine was able to induce apoptosis (as observed in MDA-MB-468 breast cancer cells) or senescence (as detected in HT-29 colorectal carcinoma cells). Annexin V-FITC/PI, caspase activation and PARP cleavage confirmed the former while positive β-gal staining corroborated the latter. Evident cell cycle perturbations were observed comprising S-phase depletion, accompanied by downregulated CDK2, and cyclins (A2, D1) with p21 upregulation. Confocal imaging of HCT-116 cells revealed induction of aberrant mitotic phenotypes - multi-nucleation, membrane blebbing and DNA-fragmentation. The DNA integrity assessment of HCT-116 and MDA-MB-468 showed irreparable damage identified by increased fluorescent γ-H2AX during the G1 cell cycle phase. Furthermore, γ-H2AX foci were visually validated in HCT-116 and MDA-MB-468 cells using confocal microscopy. Conofolidine increased oxidative stress, preceding apoptosis- and senescence-induction in most carcinoma cell lines as seen by enhanced ROS levels accompanied by NQO1 expression. Collectively, we present conofolidine as a potential anticancer candidate capable of inducing heterogeneous modes of cancer cell death in vitro, encouraging further preclinical evaluation of this natural product.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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