The alkaloid, soyauxinium chloride, displays remarkable cytotoxic effects towards a panel of cancer cells, inducing apoptosis, ferroptosis and necroptosis.

Abstract

The cytotoxic potential of a naturally occurring indoloquinazoline alkaloid, soyauxinium chloride (SCHL), was determined on a broad panel of animal and human cancer cell lines, including various sensitive and drug-resistant phenotypes. The cytotoxicity, SCHL-induced autophagic, ferroptotic, and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to detect the activity of caspases using spectrophotometric analysis. Flow cytometry was applied for cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). SCHL and doxorubicin (reference molecule) exhibited cytotoxic effects towards the 18 cancer cell lines tested. The IC50 values obtained ranged from 3.64 μM (towards CCRF-CEM leukemia cells) to 16.86 μM (against the BRAF-wildtype SKMel-505 melanoma cells for SCHL). Collateral sensitivity of the resistant HCT116 p53-/- colon adenocarcinoma cells to SCHL was observed as well as the normal sensitivity of CEM/ADR5000 leukemia cells, MDA-MB-231-BCRP breast adenocarcinoma cells and U87. MGΔEGFR glioblastoma cells. SCHL induced apoptosis in CCRF-CEM cells via caspases 3/7-, 8- and 9-activation, MMP alteration and increased ROS production, and otherwise ferroptosis and necroptosis. SCHL is a prominent cytotoxic alkaloid that should be further studied to develop a novel drug to combat cancers including refractory phenotypes.

• Authors: Armelle T Mbaveng, Cédric G T Noulala, Anne R M Samba, Simplice B Tankeo, Sara Abdelfatah, Ghislain W Fotso, Emmanuel N Happi, Bonaventure T Ngadjui, Veronique P Beng, Victor Kuete, Thomas Efferth
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 333 Pg. 109334 (Jan 05 2021) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 33245930 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Reactive Oxygen Species

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Ferroptosis (drug effects)
• Humans
• Mitochondrial Membranes (drug effects, pathology)
• Necroptosis (drug effects)
• Reactive Oxygen Species (metabolism)
• Regulated Cell Death (drug effects)