维生素C对癌干细胞(CSCs)和糖酵解的靶向作用

Vitamin C: Targeting metabolism and glycolysis in CSCs

 

NADH自荧光: 癌干细胞(CSCs)的一种新的生物标志物

 

翻译:蓝山

 

NADH自荧光是在活细胞中观察到的自动荧光的主要形式。

 

诺贝尔奖得主莱纳斯·鲍林(Linus Pauling)是第一批描述和临床测试维生素C,作为无毒抗癌药有效的人之一[30]

 

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[17]。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

 

  图1:维生素C靶向GAPDH-一种糖酵解酶

 

然而,它对CSC活动的影响以前没有评估过。在这里,我们证明了维生素C也可以用来靶向CSC,因为它是能量代谢的抑制剂,它可以进入线粒体TCA循环和OXPHOS。其他3种糖酵解抑制剂也获得了类似的结果,即2-DG、水飞蓟素和stiripentol。重要的是,stiripentol是一种临床批准的药物,但它的使用主要局限于治疗儿童癫痫发作,而不是治疗癌症[19]

 

因此,维生素C可能被证明是新的临床试验的有效药物,目的在于测试其降低癌症患者CSC活性的能力,作为一种更常规的治疗方法,以防止肿瘤复发、进一步的疾病进展和转移。

 

有趣的是,一项基于乳腺癌的临床研究已经表明,在化疗后6个月内使用维生素C可以显著降低肿瘤的复发和患者的死亡率[31,32]。然而,其潜在临床效益的机制仍然模糊不清。同样地,维生素C治疗可以抑制小鼠体内动物模型的肿瘤生长(33)

 

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 [30]. More recently, Lew Cantley’s group has revisited the mechanism(s) by which Vitamin C targets cancer cells [17]. 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 [19]. 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).

 

From www.impactjournals.com/oncotarget