Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist

Abstract

The most important biological function of vitamin B12 is to accomplish DNA synthesis, which is necessary for cell division. Cobalamin deficiency may be especially acute for rapidly dividing cells, such as glioblastoma cells. Therefore, cobalamin antagonists offer a medicinal potential for developing anti-glioma agents. In the present study, we developed an in vitro model of cobalamin deficiency in glioblastoma cells. Long-term treatment of cells with the cobalamin analogue, hydroxycobalamin [c-lactam] (HCCL) was applied to induce an increase of hypocobalaminemia biomarker. Cytometric assays demonstrated that vitamin B12 promoted glioblastoma cells proliferation, whereas the treatment of cells with HCCL caused a dramatic inhibition of cell proliferation and an induction of cell cycle arrest at the G2/M phase. Vitamin B12 counteracted all the observed effects of HCCL. In the in silico study, we characterized the molecular interactions between HCCL and transcobalamin II (TCII). We have demonstrated that HCCL shares similar interactions with TCII as naturally occurring cobalamins and therefore may act as a competitive inhibitor of this key transporter protein. We assessed the impact of HCCL on the mortality or developmental malformations of zebrafish embryos. Collectively, our findings suggest that the use of cobalamin transport antagonists as potential anti-glioma agents would be worth exploring further.

Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis

“…The important biological function of vitamin B12 is to accomplish DNA synthesis, which is necessary for cell division. All the living cells require vitamin B12 for survival and it strongly promotes glioblastoma cell proliferation; therefore, B12 deficiency is not favorable to GBM prognosis [ 50 ].…”

Daily Lifestyle Modifications to Improve Quality of Life and Survival in Glioblastoma: A Review

“…While most studies have evaluated the addition of vitamins to a treatment regimen, some data suggest that vitamin B12 deficiency is beneficial for cancer patients because of the crucial role that cobalamin plays in DNA replication. A recent in vitro study found that using a cobalamin antagonist prevents glioblastoma cell growth without inducing harm or mortality to developing healthy zebrafish embryos [ 74 ]. Elevated cobalamin levels have been linked to shorter overall survival times in multiple types of cancer including lung, hepatobiliary, colorectal, breast, head and neck, and “other tumor groups”, although glioblastoma was not specifically included [ 75 ].…”