Annual Report 2011–12

22 開拓人類知識的版圖 細胞凋亡過程包括細胞萎縮、線粒體結構 破壞和斷裂、細胞核收縮、脫氧核糖核酸 ( DNA )遭受破壞,以及一組名為半胱氨 酸蛋白酶的關鍵蛋白質活化,而半胱氨酸 蛋白酶是負責執行細胞凋亡的「劊子手」。 目前科學界普遍認為,細胞一旦展現以上 凋亡特徵,就必會死亡。但中大研究團隊發 現,正常細胞及癌細胞都能從化學物誘發 的凋亡過程中存活。 復活過來的細胞,許多染色體會變形,產生 突變。有些突變會令細胞不斷複製,變成 長生不死。換句話說,凋亡逆轉會令正常細 胞出現腫瘤細胞的特徵。至於「死裏逃生」 的癌細胞會轉化為更具侵略性和轉移性的 癌症。 幸而,研究小組初步發現,大豆異黃酮中的 主要成分金雀異黃酮,能抑制癌細胞凋亡 逆轉,未來將進行動物試驗及人體臨床試 驗,以確定其成效。 此項研究成果刊於 2012 年 6 月 15 日發行的 國際權威雜誌《細胞分子生物學》。研究團 隊的這個重大發現,為認識基礎生物學指 引出新路向,有助日後尋找抑制凋亡逆轉的 方法,提高化療治癌的效果。 mice, rats and ferrets could also reverse apoptosis. They call the phenomenon ‘anastasis’ (Greek for ‘rising to life’). It is generally believed that once the cells pass critical checkpoints, the dying process is irreversible. Such checkpoints include cell shrinkage, breakdown of mitochondria, condensation of nucleus, breakdown of DNA, and activation of a decisive group of ‘executioner’ proteins called caspases, which destroy a large number of cellular targets. But the CUHK study shows that both normal cells and cancer cells can reverse chemical- induced apoptosis. The surviving cells may bear chromosomal abnormalities and acquire mutations. Certain mutations will lead to uncontrolled cell growth and proliferation. In other words, reversal of apoptosis may cause normal cells to become carcinogenic. In the case of cancer cells, they could transform into more aggressive and metastatic cancers. The good news is that the research team found that soybean extract, with an anticancer compound known as genistein, could inhibit the recovery from apoptosis in cancer cells. In future studies, the researchers plan to test the extract on animals and carry out human clinical trials. The research team’s finding, which appeared as a high- lighted article in the 15 June issue of the Molecular Biology of the Cell , provides a new route to understanding the basic biology, and suggests new therapies such as enhancing the effect of chemotherapy by inhibiting anastasis.

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