PMC

Vitamin C improves the response of TNBC cells to buparlisib. (A) Co-treatment with vitamin C (100 μM) and buparlisib (0.5 μM) induces more apoptosis than co-treatment with buparlisib and 50 μM vitamin C or buparlisib alone (P < 0.0001) in BT20 cells. (B) Co-treatment with vitamin C (100 μM) and buparlisib (0.5 μM) induces more apoptosis than co-treatment with buparlisib and 50 μM vitamin C or buparlisib alone (P < 0.0001) in MDA-MB-453 cells. (C) Co-treatment with vitamin C (100 μM) and buparlisib (0.5 μM) almost completely blocks colony formed by BT20 cells compared to co-treatment with buparlisib and 50 μM vitamin C or buparlisib alone (P < 0.001). (D) Co-treatment with vitamin C (100 μM) and buparlisib (0.5 μM) almost completely blocks colony formed by MDA-MB-453 cells compared to co-treatment with buparlisib and 50 μM vitamin C or buparlisib alone (P < 0.001).

Vitamin C and buparlisib cooperatively decrease the expression of genes critical to cancer metastasis. (A) Western blot of fascin and FILIP1L in BT20 cells treated with vitamin C and buparlisib. (B) Semi-quantification of band density shows that vitamin C (100 μM) alone reduces fascin while buparlisib (0.5 μM) alone has no effect on fascin. (C) Semi-quantification of band density shows that vitamin C (100 μM) alone, or buparlisib (0.5 μM) alone, increases FILIP1L in BT20 cells. (D) Western blot of fascin and FILIP1L in BT20 cells treated with TETs siRNA followed by vitamin C. (E) Semi-quantification of band density shows that TETs siRNA abolishes the downregulation of fascin by vitamin C. (F) Semi-quantification of band density shows that TETs siRNA does not affect the upregulation of FILIP1L by vitamin C. (G) Western blot of fascin and FILIP1L in BT20 cells treated with vitamin C and CPI-455. (H) Semi-quantification of band density shows that CPI-455 does not affect the downregulation of fascin by vitamin C. (I) Semi-quantification of band density shows that CPI-455 abolishes the upregulation of FILIP1L by vitamin C.

Vitamin C levels in plasma (a) and gastric tissue (b). White bars are 16 WPI; Black bars are 32 WPI. Compared to gulo^−/− mice supplemented with high vitamin C (H), gulo^−/− mice supplemented with low vitamin C (L) had significantly lower plasma and gastric tissue vitamin C levels (**, p < 0.01; ***, p < 0.001). Vitamin C levels in plasma and gastric tissue in gulo^−/− mice supplemented with high vitamin C were comparable to those in C57BL/6 (wt) mice. H. pylori (Hp) infection had no significant effect on plasma vitamin C levels or gastric vitamin C levels in gulo^−/− mice supplemented with low vitamin C or in wt mice. However, gastric tissue vitamin C levels were reduced at 16 WPI but increased at 32 WPI by H. pylori infection in gulo^−/− mice supplemented with high vitamin C (*, p < 0.05).