Vitamin B₂ Sensitizes Cancer Cells to Vitamin-C-Induced Cell Death via Modulation of Akt and Bad Phosphorylation

Abstract

Vitamin C is an essential dietary nutrient that has a variety of biological functions. Recent studies have provided promising evidence for its additional health benefits, including anticancer activity. Vitamin B2, another essential dietary nutrient, often coexists with vitamin C in some fruits, vegetables, or dietary supplements. The objective of the present study is to determine whether the combination of vitamin C and B2 can achieve a synergistic anticancer activity. MDA-MB-231, MCF-7, and A549 cells were employed to evaluate the combinatory effects of vitamin C and B2. We found that the combination of vitamin C and B2 resulted in a synergistic cell death induction in all cell lines tested. Further mechanistic investigations revealed that vitamin B2 sensitized cancer cells to vitamin C through inhibition of Akt and Bad phosphorylation. Our findings identified vitamin B2 as a promising sensitizer for improving the efficacy of vitamin-C-based cancer chemoprevention and chemotherapy.

Pharmacogenomic Characterization and Isobologram Analysis of the Combination of Ascorbic Acid and Curcumin—Two Main Metabolites of Curcuma longa—in Cancer Cells

“…If applied alone, curcumin and AA were cytotoxic toward cell lines of different tumor types with curcumin exhibiting stronger cytotoxicity than AA. Our results are in line with other reports on the inhibitory activity of curcumin (Bimonte et al, 2016 ; Guzzarlamudi et al, 2016 ; Kasi et al, 2016 ; Ye et al, 2016 ; Yu et al, 2016 ; Zeng et al, 2016 ) and AA (Chen et al, 2015 ; Fukui et al, 2015 ; Jacobs et al, 2015 ; Sunil Kumar et al, 2015 ; Venturelli et al, 2015 ). The anticancer effects of curcumin in vitro and in vivo are primarily due to the activation of apoptotic pathways in cancer cells as well as the inhibition of mechanisms related to the tumor microenvironments such as inflammation, angiogenesis, invasion, and metastasis.…”

Methyl-Donors Can Induce Apoptosis and Attenuate Both the Akt and the Erk1/2 Mediated Proliferation Pathways in Breast and Lung Cancer Cell Lines

“…Additionally, it has a synergistic effect with chemotherapies [57], without having a significant impact on normal cells [55]. Similarly, vitamin B2 sensitizes cancer cells to vitamin C-induced cell death [58]. Although, vitamin B1 (thiamine) did not induce apoptosis, but reduced cell viability selectively on cancer cells, with significant increase of the basal, maximum, and ATP production oxygen consumption in MCF7 cells, but not in MCF10A.…”

Repurposing Drugs by In Silico Methods to Target BCR Kinase Domain in Chronic Myeloid Leukemia

“…Of late, vitamins are being explored for their role in the prevention and treatment of cancer. Vitamin B 2 sensitizes breast and lung cancer cell lines to vitamin C in a synergistic way by inducing cell death through the inhibition of Akt and Bad phosphorylation (Chen et al, 2015).…”