Marine Natural Product Chagosendine C Induces Copper-Dependent Cell Death and Curbs Colorectal Cancer: Mouse Study

Researchers at Shanghai University of Traditional Chinese Medicine and the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and elsewhere reported that the marine natural product chagosendine C (CHC) kills colorectal cancer cells through copper-dependent cell death, or cuproptosis. Cuproptosis is cell death that occurs when copper ions build up excessively inside cells, and it is drawing attention as a new point of attack in colorectal cancer, where recurrence and drug resistance are problems.

Raising copper and reactive oxygen inside cells and arresting the cell cycle in G1

The researchers rapidly synthesised and purified CHC, which has a metal-coordinated dimer structure, and similar alkaloids and used them in pharmacological tests. In the colorectal cancer cell lines HCT116 and RKO, CHC clearly inhibited growth and arrested the cell cycle in G1, and it also overcame resistance to oxaliplatin. In a mouse model, a dose of 40 mg per kg of body weight suppressed tumour growth, and no clear toxicity was observed. Mechanistic analysis showed that CHC targets the FDX1 (ferredoxin 1) protein and increases intracellular copper ions and reactive oxygen species (ROS).

It is significant that a natural product scaffold has been presented as an anticancer candidate that induces cuproptosis. However, these are results at the cell line and mouse experiment stage, and efficacy and safety in people and the possibility of clinical application have not been verified.