Possible Interaction: Bortezomib and Vitamin C

“Experimental Design: ATO (0.25 mg/kg) and AA (1 g) were given with an escalating dose of bortezomib (1 mg/m2 or 1.3 mg/m2 IV bolus on days 1 and 8 of a 21-day cycle).”

“Thus, while ascorbic acid was highly effective at killing EBV-positive BL cells and LCLs in vitro, it antagonized cell killing by bortezomib and was ineffective in an animal model.”

“PurposeTo investigate whether clinically relevant levels of epigallocatechin gallate (EGCG, a component of green tea) or vitamin C (ascorbic acid) could antagonize bortezomib antitumor activity in CWR22 human prostate xenograft tumors.”

“ Bortezomib (0.1 mg/kg twice a week for 4 weeks) significantly inhibits in vivo MM cell growth, which was blocked by oral vitamin C (40 mg/kg/day).”

“In this study, we examined whether daily oral intake of vitamin C inhibits antimultiple myeloma (MM) activities of bortezomib.”

“Therefore, our results for the first time show that vitamin C can significantly reduce the activity of bortezomib treatment in vivo; and importantly, suggest that patients receiving treatment with bortezomib should avoid taking vitamin C dietary supplements.”

“ Vitamin C , at orally achievable concentrations, inhibited in vitro MM cell cytotoxicity of bortezomib and blocked its inhibitory effect on 20S proteasome activity.”

“Similar to tiron, vitamin C inhibited cell death by blocking the ability of bortezomib to inhibit the proteasome.”

“In this issue, Zou et al. report that vitamin C abrogated the ability of bortezomib (PS-341, Velcade) to induce apoptosis, G2-M arrest, and cleavage of caspase 8, caspase 3, and poly(ADP-ribose) polymerase and to augment tumor necrosis factor–related apoptosis-inducing ligand–induced apoptosis”

“The delayed addition of vitamin C and/or NAC after the exposure to bortezomib alleviated the cytotoxicity in Schwann cells but not myeloma cells.”

“ Vitamin C or N-acetyl-l-cysteine (NAC) achieved near-complete rescue of Schwann cells treated with bortezomib at 30 nM or less, and these agents in combination are able to cooperatively inhibit the morphological changes and the cytotoxicity in Schwann cells with higher doses of bortezomib.”

“It was recently revealed that some flavonoids and vitamin C present in green leaves and green teas in the blood can neutralize bortezomib by directly interaction between two chemicals.”