維他命C抗癌作用的回顧

A Review on the Anti-Cancer Effect of Ascorbic Acid

維他命C 是一種重要的水溶性抗氧化劑。它曾被報告具有預防癌症及動脈硬化進行的作用，可是其抗癌作用的機轉及臨床療效卻尚未清楚。過去維他命C 抗癌的機轉被認為與其能促進膠原蛋白的產生及抑制癌細胞產生玻尿酸酵素 （hyaluronidase） 的活性以抑制癌細胞的轉移有關。最近的研究顯示，高劑量維他命C 可以直接抑制癌細胞的增殖。維他命C 直接抗癌的機轉主要由於其氧化型代謝物-dehydroascorbic acid（DHA）可經由葡萄糖轉運器（glucose transporter）進入癌細胞內部，DHA 會再被還原成維他命C，在此過程中會誘導過氧化氫（H2O2）的產生，後者進一步誘導癌細胞的凋亡（Apoptosis）。由於癌細胞之細胞膜上的葡萄糖轉換器較正常細胞多，但細胞內部清除過氧化氫的酵素卻遠少於正常細胞，因此，癌細胞遠比正常細胞更容易受到維他命C 的殺傷。臨床上有些報告指出，高劑量維他命C（每日大於或等於10g）可以延長末期癌症患者的存活期，並使少數患者的腫瘤縮小或消失，但有的報告則認為高劑量維他命C（每日10g）對癌症患者沒有任何幫助。其最大差異在於維他命C 的投與途徑，前者使用靜脈注射合併口服方式，後者則只單獨口服維他命C。藥物動力學研究顯示，只有靜脈注射方式而非口服方式才能使患者血中維他命C 濃度達到有效抗癌濃度。雖然目前尚缺乏大規模的隨機對照臨床試驗報告，但靜脈注射高劑量維他命C 的臨床抗癌療效仍值得重新審慎評估。

Ascorbic acid (AA) is an important water soluble antioxidant. It’s been previously reported that AA has preventive effects on the development of cancer and atherosclerosis. However, the anti-cancer mechanism and clinical therapeutic effect of AA remain unclear. Previously , consideration was given to the ability of AA to inhibit cancer metastasis by increasing collagen synthesis and inhibiting the activity of hyaluronidase from cancer cells. Recently, high concentration of AA was found to have direct inhibitory activities on the proliferation of cancer cells. The mechanism involved was thought to be due to the induction of apoptosis by hydrogen peroxide generated during the reductive process of DHA, an oxidized AA, which was taken up into cancer cells through glucose transporter. Cancer cells have larger numbers of glucose transporters but far less amounts of catalase to scavenge hydrogen peroxide than normal cells. Therefore, cancer cells are more susceptible to damage by AA than normal cells.Some clinical studies suggested that, high dose of AA (greater than 10 g per day) may prolong the survival of some terminal cancer patients while diminishing the tumor size in some cancer patients completely or partially. However, other studies reported no benefit of AA for cancer patients from taking high dose of AA （10g per day） The difference between these studies may be from the route of AA administration. The former studies used the intravenous route in combination with oral intake. In contrast, the latter studies used the oral intake only. Previous pharmacokinetic studies had shown that the effect cytotoxic serum concentration of AA could only be achieved though intravenous injection but not by oral intake. Despite the lack of large randomized controlled clinical trials with data for establishing the role of vitamin C in cancer therapy, the clinical activity of intravenous AA in cancer patient deserves further investigation.