Baguley Bruce C, Ding Qi, Richardson Emma
Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland , Auckland , New Zealand.
Front Oncol. 2014 Nov 5;4:310. doi: 10.3389/fonc.2014.00310. eCollection 2014.
High intravenous doses of vitamin C (ascorbic acid) have been reported to benefit cancer patients, but the data are controversial and there is incomplete knowledge of what physiological mechanisms might be involved in any response. Vitamin C is taken up efficiently by cells expressing SVCT2 transporters and since vascular endothelial cells express SVCT2, we explored the hypothesis that administration of high-dose vitamin C (up to 5 g/kg) to mice might affect vascular endothelial function. A single administration of vitamin C to mice induced time- and dose-dependent increases in plasma concentrations of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), a marker for vascular disrupting effects. Responses were comparable to those for the tumor vascular disrupting agents, vadimezan and fosbretabulin. High-dose vitamin C administration decreased tumor serotonin concentrations, consistent with the release of serotonin from platelets and its metabolism to 5-HIAA. High-dose vitamin C also significantly increased the degree of hemorrhagic necrosis in tumors removed after 24 h, and significantly decreased tumor volume after 2 days. However, the effect on tumor growth was temporary. The results support the concept that vitamin C at high dose increases endothelial permeability, allowing platelets to escape and release serotonin. Plasma 5-HIAA concentrations could provide a pharmacodynamic biomarker for vitamin C effects in clinical studies.
据报道，静脉注射高剂量维生素C（抗坏血酸）对癌症患者有益，但数据存在争议，对于任何反应可能涉及的生理机制也了解不全面。表达SVCT2转运蛋白的细胞能够有效摄取维生素C，由于血管内皮细胞表达SVCT2，我们探究了向小鼠施用高剂量维生素C（高达5 g/kg）可能影响血管内皮功能的假说。给小鼠单次施用维生素C会导致血清素代谢物5-羟吲哚乙酸（5-HIAA）的血浆浓度出现时间和剂量依赖性增加，5-HIAA是血管破坏作用的标志物。其反应与肿瘤血管破坏剂vadimezan和磷丙泊酚二钠的反应相当。高剂量维生素C给药会降低肿瘤血清素浓度，这与血清素从血小板释放并代谢为5-HIAA一致。高剂量维生素C还显著增加了24小时后切除的肿瘤内出血性坏死的程度，并在2天后显著减小了肿瘤体积。然而，对肿瘤生长的影响是暂时的。这些结果支持了高剂量维生素C会增加内皮通透性，使血小板逸出并释放血清素这一概念。血浆5-HIAA浓度可为临床研究中维生素C的作用提供药效学生物标志物。
