Melittin誘發人類口腔癌細胞凋亡之分子機轉

口腔癌是一種高致死率的疾病，在台灣地區口腔癌近年來也已進入國人十大癌症死亡原因之ㄧ。研究指出利用細胞凋亡的作用機制可以將癌細胞除去，尤其對於作用口腔鱗狀癌細胞是一種有效的策略，所以本文主要探討蜜蜂蜂毒Melittin作用於口腔癌細胞株造成細胞凋亡現象及其路徑。首先，於實驗結果發現Melittin會對口腔癌細胞產生細胞毒性，並可誘發細胞死亡。當Melittin的濃度為5μg/ml與7.5μg/ml時，細胞存活率分別降低30%與53%。進一步利用細胞核染色分析觀察口腔癌細胞於Melittin作用後細胞凋亡的型態，結果發現經由藥物處理其細胞核有濃縮及少數核斷裂成碎片的現象，從細胞型態學的觀察證實Melittin可誘發細胞凋亡。在西方點墨法的實驗發現Melittin對熱休克蛋白60與熱休克蛋白70蛋白表現量未影響，但在熱休克蛋白27表現量隨著藥物劑量不同，而有不同程度的蛋白表達量下降。此外在MAPK家族的訊息傳遞路徑中，觀察到p38蛋白磷酸化表現量增加，而ERK1/2蛋白磷酸化表現量則是下降。綜合以上實驗結果得知Melittin的作用會促使口腔癌細胞的死亡，且抗凋亡蛋白熱休克蛋白27的蛋白表現量減少，並藉由p38-dependent路徑伴隨著ERK1/2蛋白磷酸化表現量減低而走向細胞凋亡。

關鍵字

蜂毒；細胞凋亡；熱休克蛋白；口腔癌

並列摘要

Oral cancer has a high mortality in Taiwan. Recently, the targeted elimination of cancer cells by inducing apoptosis has appeared as a valued treatment strategy for oral squamous cell carcinoma (OSCC). In this study, we discuss the molecular mechanism of melittin induced apoptosis in squamous cell carcinoma-4 (SCC-4) cells. These data indicate that 12 h melittin treatment inhibited cell viability in a dose-dependent manner, resulting in a 30% and 53% reduction of viable cells at 5 and 7.5μg/ml, respectively. SCC-4 cells treated with 5μg/ml melittin for 12 h exhibited apoptotic features and fragmentation of DNA. Western blot analysis of melittin treated SCC-4 cells revealed a dramatically reduction of heat shock protein 27 (HSP27), while HSP60 and HSP70 were not. Follow, the analyzed the MAPK family proteins’ expression (ERK 1/2 and p38). We found melittin cause phospharylation p38 protein expression increase and decreased phospharylation ERK 1/2 protein expression. Base on those results, we thought the molecular mechanism of melittin-induced in human oral cancer cells may through HSP27 protein decreased and has a relationship with phospharylation p38 protein increased with phospharylation ERK 1/2 proetin expression decreased.

並列關鍵字

Melittin ； Apoptosis ； Heat shock protein ； Oral cancer

參考文獻

Banerji U., Sain N., Sharp S. Y., Valenti M., Y. Asad, Ruddle R., Raynaud F., Walton M., Eccles S. Judson A., I., Jackman A. L. and Workman P. 2008. An in vitro and in vivo study of the combination of the heat shock protein inhibitor 17-allylamino-17-demethoxygeldanamycin and carboplatin in human ovarian cancer models. Cancer chemotherapy and pharmacology. 62: 769-778.

Bechinger B. and Lohner K. 2006. Detergent-like actions of linear amphipathic cationic antimicrobial peptides. Biochimica et Biophysica Acta. 1758: 1529–1539.

Boffetta P., Hecht S., Gray N., Gupta P. and Straif K. 2008. Smokeless tobacco and cancer. The lancet oncology. 9: 667-675.

Chen J. C., Lu K. W., Tsai M. L, Hsu S. C., Kuo C. L., Yang J. S., Hsia T. C., Yu C. S., Chou S. T., Kao M. C., Chung J. G. and Wood W. G. 2009. Gypenosides induced G0/G1 arrest via CHk2 and apoptosis through endoplasmic reticulum stress and mitochondria-dependent pathways in human tongue cancer SCC-4 cells. Oral Oncology. 45: 273-283.

Chen P. N., Hsieh Y. S., Chiang C. L., Chiou H. L., Yang S. F. and Chu S. C. 2006. Silibinin inhibits invasion of oral cancer cells by suppressing the MAPK Pathway. Journal of dental research. 85 (3): 220-225.

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Melittin誘發人類口腔癌細胞凋亡之分子機轉

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