Verrax Julien, Cadrobbi Julie, Delvaux Marianne, Jamison James M, Gilloteaux Jacques, Summers Jack L, Taper Henryk S, Buc Calderon Pedro
Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Département des sciences pharmaceutiques, Université Catholique de Louvain, Brussels, Belgium.
Eur J Med Chem. 2003 May;38(5):451-7. doi: 10.1016/s0223-5234(03)00082-5.
Deficiency of alkaline and acid DNase is a hallmark in all non-necrotic cancer cells in animals and humans. These enzymes are reactivated at early stages of cancer cell death by vitamin C (acid DNase) and vitamin K(3) (alkaline DNase). Moreover, the coadministration of these vitamins (in a ratio of 100:1, for C and K(3), respectively) produced selective cancer cell death. Detailed morphological studies indicated that cell death is produced mainly by autoschizis, a new type of cancer cell death. Several mechanisms are involved in such a cell death induced by CK(3), they included: formation of H(2)O(2) during vitamins redox cycling, oxidative stress, DNA fragmentation, no caspase-3 activation, and cell membrane injury with progressive loss of organelle-free cytoplasm. Changes in the phosphorylation level of some critical proteins leading to inactivation of NF-kappaB appear as main intracellular signal transduction pathways. The increase knowledge in the mechanisms underlying cancer cells death by CK(3) may ameliorate the techniques of their in vivo administration. The aim is to prepare the introduction of the association of vitamins C and K(3) into human clinics as a new, non-toxic adjuvant cancer therapy.
碱性和酸性脱氧核糖核酸酶（DNase）缺乏是动物和人类所有非坏死性癌细胞的一个标志。这些酶在癌细胞死亡的早期阶段可被维生素C（酸性DNase）和维生素K(3)（碱性DNase）重新激活。此外，同时给予这些维生素（维生素C和维生素K(3)的比例分别为100:1）可导致选择性癌细胞死亡。详细的形态学研究表明，细胞死亡主要由自噬裂（一种新型的癌细胞死亡方式）引起。CK(3)诱导的这种细胞死亡涉及多种机制，包括：维生素氧化还原循环过程中产生过氧化氢、氧化应激、DNA片段化、无半胱天冬酶-3激活以及细胞膜损伤并伴有无细胞器细胞质的逐渐丧失。导致核因子κB失活的一些关键蛋白磷酸化水平的变化似乎是主要的细胞内信号转导途径。对CK(3)诱导癌细胞死亡机制的进一步了解可能会改善其体内给药技术。目的是将维生素C和维生素K(3)联合应用引入人类临床，作为一种新型的无毒辅助癌症治疗方法。
