Mastrangelo Domenico, Pelosi Elvira, Castelli Germana, Lo-Coco Francesco, Testa Ugo
Department of Medical, Surgical and Neurological Sciences, University of Siena, Polo Scientifico San Miniato, Siena, Italy.
Department of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Blood Cells Mol Dis. 2018 Mar;69:57-64. doi: 10.1016/j.bcmd.2017.09.005. Epub 2017 Sep 21.
Vitamin C (Vit C or Ascorbate) is essential for many fundamental biochemical processes. Vit C is an essential nutrient with redox functions at normal physiologic concentrations. The main physiologic function of this vitamin is related to its capacity to act as a co-factor for a large family of enzymes, collectively known as Fe and 2-oxoglutarate-dependent dioxygenases. It also modulates epigenetic gene expression through the control of TET enzymes activity. Vit C also has several biological properties allowing to restore the deregulated epigenetic response observed in many tumors. High-dose Vit C has been investigated as a treatment for cancer patients since the 1969. Pharmacologic ascorbate acts as a pro-drug for hydrogen peroxide formation (HO) and, through this mechanism, kills cancer cells. To achieve high in vivo concentrations, Ascorbate must be injected by i.v. route. Initial clinical studies of Ascorbate cancer treatment have provided encouraging results, not confirmed in subsequent studies. Recent clinical studies using i.v. injection of high-dose Ascorbate have renewed the interest in the field, showing that significant anti-tumor activity. Pre-clinical studies have led to identify tumors sensitive to Ascorbate that could potentially benefit from this treatment either through an epigenetic modulator effect or through tumor killing by oxidative stress.
维生素C（Vit C或抗坏血酸盐）对许多基本生化过程至关重要。在正常生理浓度下，维生素C是一种具有氧化还原功能的必需营养素。这种维生素的主要生理功能与其作为一大类酶（统称为铁和2-氧戊二酸依赖性双加氧酶）的辅助因子的能力有关。它还通过控制TET酶的活性来调节表观遗传基因表达。维生素C还具有多种生物学特性，能够恢复在许多肿瘤中观察到的失调的表观遗传反应。自1969年以来，高剂量维生素C已被研究用于癌症患者的治疗。药理抗坏血酸盐作为过氧化氢形成（HO）的前体药物，并通过这种机制杀死癌细胞。为了在体内达到高浓度，必须通过静脉注射途径注射抗坏血酸盐。抗坏血酸盐癌症治疗的初步临床研究取得了令人鼓舞的结果，但在随后的研究中未得到证实。最近使用静脉注射高剂量抗坏血酸盐的临床研究重新激发了该领域的兴趣，显示出显著的抗肿瘤活性。临床前研究已确定对抗坏血酸盐敏感的肿瘤，这些肿瘤可能通过表观遗传调节剂作用或通过氧化应激杀死肿瘤而从这种治疗中受益。
