维生素C杀灭 肿瘤的种子-肿瘤干细胞生长方面的功效是常用药物的10倍
NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting “stemness”
日期:2017年3月8日,
来源:英国索尔福德大学University of Salford
研究人员测量了3种天然物质、3种实验性药物和1种临床药物对癌干细胞代谢的影响。
据英国索尔福德的科学家说，维生素C在杀灭癌干细胞生长方面的功效是2-脱氧葡萄糖（2-DG）的10倍。
这项发表在Oncotarget上的研究首次证明了维生素C(抗坏血酸)可以用来攻击和杀死癌干细胞(CSCs)，这是导致肿瘤致命的罪魁祸首。
索尔福德大学转化医学 迈克尔·P·Lisanti
教授说:“我们一直在关注如何针对癌干细胞的天然物质包括水飞蓟素(Silibinin)和咖啡酸苯酯CAPE-一种蜜蜂提取物，但到目前为止最令人兴奋的是维生素C的作用。
“维生素C是廉价的、天然的、无毒的，而且很容易获得，所以它作为对抗癌症的潜在武器将是一个重要的步骤。”
癌干细胞样细胞被认为是化疗耐药的根本原因，导致晚期疾病患者的治疗失败和肿瘤复发和转移的诱发因素(regrowth)。
索尔福德团队开始评估癌干细胞的生物能量，即允许细胞存活和生长的过程，以扰乱它们的新陈代谢。
重点研究能量转移，他们测量了7种物质在实验室对癌干细胞系的影响，临床批准的药物stiripentol(用于治疗儿童癫痫症）, 3种天然产物——咖啡酸苯酯(CAPE)，硅胶和抗坏血酸，以及实验药物，如actinonin, FK866和2 - DG。
他们发现天然的抗生素actinonin和复方FK866是最有效的，天然产物也抑制了CSC的形成，维生素C的效力是2 – DG的10倍。
在诺贝尔奖得主莱纳斯·鲍林(Linus Pauling)的研究中，维生素C曾被证明是一种有效的无毒抗癌药物，最近被证明在日本乳腺癌患者中使用，其死亡率降低了25%。然而，它对癌干细胞活动的影响尚未被评估，在这方面，它表现为糖酵解的抑制剂，在线粒体中产生能量，线粒体是细胞的“能量工厂”。
研究报告的主要作者、索尔福德团队的另一名成员格洛丽亚·博努切利博士补充说:“这进一步表明，维生素C和其他无毒化合物可能在抗癌斗争中发挥作用。”
“我们的研究结果表明，它是一种很有前途的临床试验药物，而且是一种更常规疗法的辅助治疗剂，可以预防肿瘤复发、进一步的疾病进展和转移。”
研究发现，维生素C杀死癌干细胞的机理是作为促氧化剂和糖酵解抑制剂（抑制GAPDH-一种糖酵解关键的酵素的活性），其IC-50(达到最大抑制浓度的一半）只是1mM。维生素C杀死癌干细胞的效力是2-脱氧-葡萄糖的10倍。
Vitamin C effective in targeting cancer stem cells
Date:March 8, 2017
Source:University of Salford
Summary:
Researchers have measured the impact on cancer stem cell metabolism of three natural substances, three experimental pharmaceuticals and one clinical drug.
Researchers measure the impact on cancer stem cell metabolism of 3 natural substances, 3 experimental pharmaceuticals and 1 clinical drug.
https://www.sciencedaily.com/releases/2017/03/170308083940.htm
Vitamin C is up to ten times more effective at stopping cancer cell growth than pharmaceuticals such as 2-DG, according to scientists in Salford, UK.
The research, published in Oncotarget, is the first evidence that Vitamin C (ascorbic acid) can be used to target and kill cancer stem cells (CSCs), the cells responsible for fuelling fatal tumours.
Dr Michael P. Lisanti, Professor of Translational Medicine at the University of Salford, said: "We have been looking at how to target cancer stem cells with a range of natural substances including silibinin (milk thistle) and CAPE, a honey-bee derivative, but by far the most exciting are the results with Vitamin C.
"Vitamin C is cheap, natural, non-toxic and readily available so to have it as a potential weapon in the fight against cancer would be a significant step."
Cancer stem-like cells are thought to be the root cause of chemotherapy resistance, leading to treatment failure in patients with advanced disease and the triggers of tumour recurrence and metastasis (regrowth).
The Salford team set out to assess the bioenergetics of cancer stem cells -- the processes which allow the cells to live and thrive -- with a view to disrupting their metabolism.
Focusing on energy-transfer, they measured the impact on cell lines in a laboratory of 7 substances, the clinically-approved drug stiripentol, 3 natural products -- caffeic acid phenyl ester (CAPE), silibinin and ascorbic acid -- and experimental pharmaceuticals, such as actinonin, FK866 and 2-DG.
While they found that natural antibiotic actinonin and the compound FK866 were the most potent, the natural products also inhibited CSC formation, with Vitamin C, outperforming 2-DG by tenfold in terms of potency.
Vitamin C has previously been shown to be effective as a non-toxic anti-cancer agent in studies by Nobel Prize winner Linus Pauling and was recently shown to reduce mortality by 25% on breast cancer patients in Japan. However, its effects on CSC activity have not been previously evaluated and in this context, it behaves as an inhibitor of glycolysis, which fuels energy production in mitochondria, the "powerhouse" of the cell.
Dr Gloria Bonuccelli, lead author and another member of the Salford team added: "This is further evidence that Vitamin C and other non-toxic compounds may have a role to play in the fight against cancer.
"Our results indicate it is a promising agent for clinical trials, and a as an add-on to more conventional therapies, to prevent tumour recurrence, further disease progression and metastasis."
Story Source:
Materials provided by University of Salford. Note: Content may be edited for style and length.
Journal Reference:
Gloria Bonuccelli, Ernestina Marianna De Francesco, Rianne de Boer, Herbert B. Tanowitz, Michael P. Lisanti. NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting “stemness”. Oncotarget, 2015; DOI: 10.18632/oncotarget.15400
REFERENCES:
https://www.sciencedaily.com/releases/2017/03/170308083940.htm
