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维生素C与K3联合在癌症治疗中的潜在治疗应用。

Potential therapeutic application of the association of vitamins C and K3 in cancer treatment.

作者信息

Calderon P Buc, Cadrobbi J, Marques C, Hong-Ngoc N, Jamison J M, Gilloteaux J, Summers J L, Taper H S

机构信息

Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Faculté de Médecine, Université Catholique de Louvain, Bruxelles, Belgium.

出版信息

Curr Med Chem. 2002 Dec;9(24):2271-85. doi: 10.2174/0929867023368674.

Abstract

The decision of stressed cells to die or to survive is made by integrating signals at different levels through multiple check points. However, initiation and continued progression toward cell death by apoptosis in cancer cells may be blocked by mutation of the tumor suppressor p53 or overexpression of members of the bcl-2 family of proteins. The existence of such mechanisms indicates that cancer cells lose the controls regulating their cell cycle. Therefore, the activation of their programmed cell death appears as a major therapeutic target. Oxidative stress can stimulate growth, trigger apoptosis, or cause necrosis depending upon the dose and the exposure time of the oxidizing agent. A large body of evidence supports the idea that oxidative stress induced by redox cycling of vitamins C and K(3) in association surpasses cancer cellular defense systems and results in cell death. The molecular mechanisms underlying such a process are, however, still unknown. Indeed, several types of cell death may be produced, namely autoschizis, apoptosis and necrosis. Combined vitamin C and K(3) administration in vitro and in vivo produced tumor growth inhibition and increased the life-span of tumor-bearing mice. CK(3)-treatment selectively potentiated tumor chemotherapy, produced sensitization of tumors resistant to some drugs, potentiated cancer radiotherapy and caused inhibition of the development of cancer metastases without inducing toxicity in the host. We propose the association of vitamins C and K(3) as an adjuvant cancer therapy which may be introduced into human cancer therapy without any change in the classical anticancer protocols, and without any supplementary risk for patients.

摘要

应激细胞决定死亡还是存活是通过多个检查点在不同水平整合信号来做出的。然而,癌细胞中通过凋亡引发并持续走向细胞死亡的过程可能会因肿瘤抑制因子p53的突变或bcl-2蛋白家族成员的过表达而受阻。此类机制的存在表明癌细胞失去了调节其细胞周期的控制。因此,激活其程序性细胞死亡似乎是一个主要的治疗靶点。氧化应激可根据氧化剂的剂量和暴露时间刺激生长、引发凋亡或导致坏死。大量证据支持这样一种观点,即维生素C和K(3)的氧化还原循环联合诱导的氧化应激超过了癌细胞的防御系统并导致细胞死亡。然而,这一过程背后的分子机制仍然未知。的确,可能会产生几种类型的细胞死亡,即自体分解、凋亡和坏死。维生素C和K(3)在体外和体内联合给药可抑制肿瘤生长并延长荷瘤小鼠的寿命。CK(3)治疗选择性地增强了肿瘤化疗效果,使对某些药物耐药的肿瘤产生敏感性,增强了癌症放疗效果,并抑制了癌症转移的发展,而不会在宿主中诱导毒性。我们提出将维生素C和K(3)联合作为一种辅助癌症治疗方法,可在不改变经典抗癌方案且不给患者带来任何额外风险的情况下引入人类癌症治疗。

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