Rescue of Methionine Dependence by Cobalamin in a Human Colorectal Cancer Cell Line

Area of Science:

• Biochemistry
• Cell Biology
• Oncology

Background:

• Methionine dependence is a hallmark of many cancer cells, hindering proliferation when methionine is absent.
• This dependence is not linked to methionine synthase defects but may involve cobalamin (vitamin B12) metabolism.
• Normal cells are methionine-independent, thriving when methionine is replaced by homocysteine.

Purpose of the Study:

• To investigate the role of cobalamin in methionine dependence in a human colorectal cancer cell line.
• To determine the mechanism by which cobalamin supplementation affects cancer cell proliferation under methionine deprivation.

Main Methods:

• Culturing human SW48 colorectal cancer cells in methionine-free media supplemented with L-homocystine.
• Supplementing media with varying levels of cyanocobalamin.
• Assessing cell proliferation, apoptosis, and reactive oxygen species production.
• Analyzing the integrated stress response (ISR) activation.

Main Results:

• Cyanocobalamin supplementation (1 µg/mL) restored proliferation in SW48 cells in methionine-free media.
• Methionine replacement with L-homocystine halted proliferation without increasing apoptosis or reactive oxygen species.
• Cyanocobalamin prevented ISR activation and subsequent cell cycle arrest in methionine-deprived SW48 cells.

Conclusions:

• Cobalamin supplementation can rescue methionine-dependent proliferation in SW48 colorectal cancer cells.
• The protective effect of cyanocobalamin is mediated by the prevention of the integrated stress response.
• This study reveals cell-line-specific responses to cobalamin in the context of cancer cell methionine dependence.