Vitamin C： Targeting metabolism and glycolysis in CSCs
最近，卢·坎特利的研究小组重新研究了维生素C对癌细胞的作用机制。有趣的是，他们发现维生素C有两种作用机制。首先，它是一种强力的 助氧化剂，它能有效地消耗还原性谷胱甘肽（GSH）池，从而导致细胞氧化应激和癌细胞凋亡。此外，它还表现为糖酵解的抑制剂，通过靶向GAPDH的活性，一种关键的糖酵解酶。 图1
Vitamin C Targeting metabolism and glycolysis in CSCs
NADH auto-auorescence: A new biomarker for CSCs
NADH auto-fluorescence is the dominant form of auto-fluorescence observed in living cells.
The Noble Prize winner, Linus Pauling, was among the first to describe and clinically test the efficacy of Vitamin C, as a relatively non-toxic anti-cancer agent . More recently, Lew Cantley’s group has revisited the mechanism(s) by which Vitamin C targets cancer cells . Interestingly, they showed that Vitamin C has two mechanisms of action. First, it is a potent pro-oxidant, that actively depletes the reduced glutathione pool, leading to cellular oxidative stress and apoptosis in cancer cells. Moreover, it also behaves as an inhibitor of glycolysis, by targeting the activity of GAPDH, a key glycolytic enzyme. However, its effects on CSC activity was not previously evaluated. Here, we show that Vitamin C can also be used to target the CSC population, as it is an inhibitor of energy metabolism that feeds into the mitochondrial TCA cycle and OXPHOS. Similar results were also obtained with 3 other glycolysis inhibitors, namely 2-DG, silibinin and stiripentol. Importantly, stiripentol is a clinically-approved drug, but its use is mainly restricted to the treatment of epileptic seizures in children, and not for cancer therapy . Thus, Vitamin C may prove to be promising agent for new clinical trials, aimed at testing its ability to reduce CSC activity in cancer patients, as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression and metastasis. Interestingly, a breast cancer based clinical study has already shown that the use of Vitamin C, concurrent with or within 6 months of chemotherapy, significantly reduces both tumor recurrence and patient mortality [31,32]. However, the mechanism underlying its potential clinical benefit remained obscure. Similarly, Vitamin C treatment inhibits tumor growth in murine animal models in vivo(33).