基隆山藥皂苷對癌細胞生長抑制與凋亡作用之研究

The Growth-Inhibitory and Apoptotic Effects of Saponins of Keelung Yam (Dioscorea Pseudojaponica Yamamoto) on Cancer Cell Lines

陳佳禧(Chia-Hsi Chen)

指導教授 ： 王進崑 ； 陳肅霖

中山醫學大學/健康管理學院/營養學研究所/碩士(2009年)

https://doi.org/10.6834/CSMU.2009.00139

摘要

山藥含有豐富的皂苷，屬類固醇皂苷，為山藥所含最具生理活性的重要化合物；從其他植物類固醇皂苷的研究發現，醣基於皂苷的生理活性上扮演著相當重要的角色，其所接醣基的多寡與有無，醣基的組成、醣苷的鍵結型式、醣基鏈的長度及支鏈的有無等，皆會影響其生理功效；故不同形式配醣體的的皂苷，及水解後造成醣基去除而形成皂苷元，因其結構的不同，產生之生理功效亦不盡相同。
然由於目前對於山藥類固醇皂苷及皂苷元間結構差異所造成的生理代謝與生物活性之研究甚少，仍不甚明瞭，因此本研究以臺灣基隆山藥為原料，分離出furostanol glycosides（FUG）和spirostanol glycosides（SPG）等不同形式配醣體結構之皂苷，並與不含醣基之薯蕷皂苷元（diosgenin；DIO）進行實驗，探討山藥皂苷抗癌之功效與機制，並進ㄧ步探討比對此些功效與機制是否因山藥皂苷配醣體結構（furosten和spirosten）形式之不同，以及醣基之有無而有所差異。
本研究發現，山藥固醇類皂苷及皂苷元抑制MCF-7乳癌、A549肺癌及Hep G2肝癌等癌細胞之功效，依序為SPG＞DIO＞FUG，且相當優於抗癌藥物5-fluorouracil及methotrexate；其選毒性與安全性方面，發現FUG＞DIO＞SPG；因此，FUG或許是固醇類皂苷及皂苷元發展抗癌藥物的方向；而SPG優異之抗癌效果，或可直接作用於對其高度敏感的癌細胞或癌組織中心，或往標靶治療方向發展。進一步的研究發現，山藥固醇類皂苷及皂苷元抑制MCF-7乳癌細胞的功效，主要是誘發G0/G1期停滯，造成細胞凋亡；其透過的機制是經由p53促凋亡蛋白的增加，及AKT（具抗凋亡功能）與BRCA-1（具DNA修復功能）等抗凋亡蛋白被抑制，達到雙重細胞凋亡之抗癌效果；其中SPG處理之MCF-7肺癌細胞具早期大量誘發p53蛋白的特性，或許是SPG優異抗癌效果之原因。

關鍵字

山藥 ； 皂苷凋亡 ； furostanol glycosides ； spirostanol glycosides

並列摘要

Saponins, steroid saponins, which are rich and play the most important physiologically active compounds in yam. The studies of steroid saponins of other plants found that glycone on saponins played an important physiological activity. Because of the structural differences between saponin glycosides with different forms and sapogenin resulting from the removal of glycone by hydrolysis on saponins , caused the different physiological effect.
The research is little and unclear about the physiological metabolism and biological activity caused by structural differences between yam steroid saponins and sapogenin. In this study, therefore, the furostanol glycosides (FUG) and spirostanol glycosides (SPG) with different forms of glycoside, and diosgenin (DIO) with no glycone were isolated from yam (Dioscorea Pseudojaponica Yamamoto in Taiwan) that were investigated the effect and mechanism on anti-cancer for the structurally different Saponins and sapogenin.
The study found that the rank for the anti-cancer effect on A549 lung adenocarcinoma cells、Hep G2 hepatocellular carcinoma cells and MCF-7 breast adenocarcinoma cells by yam steroid sapogenin and saponin is SPG ＞ DIO ＞ FUG, all are rather better than anti-cancer drugs for 5-fluorouracil and methotrexate on anti-cancer effect. The rank for the selective toxicity and safety on clone-9 normal rat liver cells and HS68 normal human foreskin fibroblasts is FUG > DIO > SPG. Yam steroid saponins and sapogenin are resulting in MCF-7 cells apoptosis by arrested the G0/G1 phase, increased the p53 protein with promoting apoptosis and decreased the AKT protein with anti-apoptosis and the BRCA-1 protein with repairing DNA. And, SPG has the excellent anti-cancer effect on MCF-7 cells may be due to induced much of the p53 protein in the early treated stage.

並列關鍵字

Yam (Dioscorea spp.) ； saponin ； apotosis ； furostanol glycosides ； spirostanol glycosides

參考文獻

王昭月、賴永昌、譚增偉、劉新裕。1992。山藥之生產促進及省工栽培研究。中華農業研究 41: 43-52。

劉新裕、張同吳、王昭月、徐原田、胡敏夫。1997。山藥台農2號之生產促進。中華農業研究 46: 249-261。

Chen, A. H. 1985. Applied studies on the saponins of Dioscorea I. Studies on the saponins of Dioscorea in Taiwan. J. Chin. Chem. Soc. 43: 79-85.

Wang, J. Y., Liu, S. Y., Son, L. M. and Kao, C. C. 1993. Genetic and agronomic variation among yam genotypes. J. Agric. Res. China 42 : 280-291.

陳儀驊。2001。山藥、芋頭及甘藷黏質對澱粉理化性質之影響。靜宜大學食品營養研究所碩士論文。台中。