Ascorbic acid inhibits antitumor activity of bortezomib in vivo

Department of Medical Oncology, LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 10.43). 05/2009; 23(9):1679-86. DOI: 10.1038/leu.2009.83
Source: PubMed


Earlier studies have shown that ascorbic acid (vitamin C) inhibits bortezomib-induced cytotoxicity against cancer cells in vitro. However, the clinical significance of vitamin C on bortezomib treatment is unclear. In this study, we examined whether daily oral intake of vitamin C inhibits antimultiple myeloma (MM) activities of bortezomib. Vitamin C, at orally achievable concentrations, inhibited in vitro MM cell cytotoxicity of bortezomib and blocked its inhibitory effect on 20S proteasome activity. Specifically, plasma collected from healthy volunteers taking 1 g/day vitamin C reduced bortezomib-induced MM cell death in vitro. This antagonistic effect of vitamin C against proteasome inhibitors is limited to the boronate class of inhibitors (bortezomib and MG262). In vivo activity of this combination treatment was then evaluated using our xenograft model of human MM in SCID (severe combined immune-deficient) mice. 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). 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.

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Available from: Gullu Gorgun, Jul 09, 2014
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    • "We hope to inspire the discussion about the safety of any herbal formulas in combination with cytotoxic therapies and encourage physicians to seek faithful conversations dealing with the use of CAM in cancer patients. There are several reports on the detrimental effects of CAM on the efficacy of chemotherapeutic agents such as St. John’s wort with irinotecan or imatinib [7] or ascorbic acid and green tea with bortezomib [8,9] to name but a few. Therefore, we think that a comprehensive management of our patients should also include education about the risk of interactions with herbal formulas. "
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    • "Bortezomib has also shown poor efficacy in the treatment of chronic lymphocytic leukemia (CLL), despite potent in vitro activity4,5. Recently, it was found that some of dietary flavonoids and vitamin C have antagonistic interaction with bortezomib which affects the anti-cancer property of this drug6-9. According to that 77% of patients use vitamins or herbs concurrently with conventional anticancer treatment10, here we review current knowledge concerning how dietary intake could counteract chemotherapy with bortezomib. "
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    • "AA is commonly used in complementary and alternative medicine (Gonzalez et al., 2005; Padayatty et al., 2010). Chemical composition and biological activities of AA have long been investigated for antioxidant (Arab and Ehsanpour , 2006), antitumor (Perrone et al., 2009), antiproliferative (Belin et al., 2009), antigenotoxic (Siddique et al., 2005), ameliorative (Ambali et al., 2010), and antimutagenic (Aly and Donya, 2002; Narayana, 2010; Türkez, 2011) properties. On the other hand, imazalil (IMA) (C 14 H 14 Cl 2 N 2 O) is a fungicide that is used commonly in fruit plantations and postharvest treatments but has teratogenic effects on vertebrate development (Zega et al., 2009). "
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