Autoschizis（細胞自裁）－－一種新的細胞死亡型態及其未來之臨床應用

Autoschizis- A Novel Cell Death and Clinical Application in Cancer Therapy

維他命C過去被認為是一種重要的水溶性抗氧化劑，不但可以預防壞血病，而且可以保護正常細胞免於氧化壓力的傷害；維他命K3則為水溶性合成維他命K，被用於治療因新生兒或成年人肝病引起之維他命K不足所導致的出血。自1987年開始，學者們發現高劑量的維他命C加上維他命K3，對於癌細胞增殖有相加乘的抑制作用。動物實驗結果顯示，維他命C與維他命K3（在100:1比率下）合併治療，不但可以抑制癌細胞的轉移，還可以延長接種癌細胞之實驗動物的存活期。維他命C和維他命K3抗癌的共通主要機轉是：提高癌細胞內部氧化壓力，誘導癌細胞的自我凋亡（apoptosis）及壞死（necrosis）。當高劑量的維他命C和維他命K3二者合併使用時，會造成大量癌細胞的死亡。其細胞死亡的形態與過去所熟知的壞死和細胞凋亡不同，而是兩者的合併，此情形稱為 Autoschizis（細胞自裁）。細胞自裁（Autoschizis）是自動裂解的意思，其特徵是細胞膜呈泡狀，細胞器自我切割，細胞變形及縮小，以及細胞核變小等形態學上的改變。雖然目前尚缺乏大規模的臨床試驗報告，但由於高劑量維他命C合併維他命K3的安全性高、副作用小，而且價格低廉容易取得，將來或許可以發展成為一種新的癌症輔助療法，以加強放療或化療的效果。

Vitamin C is considered to be an important watery anti-oxidant. It not only can prevent scurvy, but also prevent normal cells from damage by oxidative stress. On the other hand, vitamin K3, a watery type of synthetic vitamin K, is applied to treat bleeding, which resulted from vitamin K deficiency due to neonatal or adult liver disease. Since 1987, a combination of high doses of vitamin C along with vitamin K3 were found to have synergistically inhibitory effect on the proliferation of cancer cells. This effect is more evident when the ratio of vitamin C to vitamin K is 100:1. The animal study revealed that, a combination of vitamin C and vitamin K3 could inhibit the metastasis of cancer cells and prolong the life-span of animals, but has fewer side-effects. The major mechanism of anti-cancer effects from vitamin C combined with vitaminK3 is considered to be through the increase of intracellular oxidative stress, especially the massive production of hydrogen peroxide (H2O2). The latter can induce apoptosis and necrosis of cancer cells. When high concentrations of vitamin C and vitamin K3 are added into the culture medium of cancer cells simultaneously, they can induce massive death of cancer cells. The type of cell death is different from necrosis and apoptosis, but is shown as the combination of two phenomena. This special pattern ofcell death is called “autoschizis”. The meaning of autoschizis is auto-split. The biological characteristics of autoschizis include vesicle change of cell membrane, self-excision of organelles, deformity and shrinkage of cells and decreased size of nucleus. In clinics, vitamin C combined with vitamin K3 was found to inhibit the progression of prostate cancer in a small pilot clinical study. So far, there is still a lack of large-scale clinical trials. However, both of these two agents are cheap and safe. In the future, the combination of vitamin C and vitamin K3 may be developed to be a supportive therapeutic method to enhance the anti-cancer effect of chemotherapy or radiotherapy.