檳榔子（areca nut, AN）是一個在世界上受歡迎卻具致癌性的咀嚼物，但有關其成份對細胞毒性的效應研究卻非常有限。我們先前證實了檳榔子與檳榔子萃取液（areca nut extract, ANE）可分別誘導細胞凋亡與自體吞噬，而存在於檳榔子萃取液中的自體吞噬誘導活性則位於經部份純化後的30-100 kDa中（標示為ANE 30-100K）。ANE 30-100K多半由醣類組成，而其中所含的蛋白質則小於2%。其誘導自體吞噬的活性對纖維酶與蛋白酶K敏感，顯示其身份可能為蛋白醣（或醣蛋白）。這些發現對檳榔子的致病機轉提供了一項新的洞見，並可藉此提供一個檳榔子成份誘導不同死亡形式的理想研究模式。我們最近的研究結果顯示（1）ANE 30-100K可誘導AMP-activated protein kinase（AMPK）的活化，並且Compound C可抑制ANE 30-100K所誘導的自體吞噬；（2）而檳榔子與ANE 30-100K均能刺激ERK1/2的磷酸化；（3）可將細胞液加入覆蓋有ANE 30-100K的培養孔中，得到幾個結合於其上的未知蛋白（根據以往的經驗足以再作胺基酸定序分析），故本計劃未來的工作包含： a. calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMPK訊息途徑分別在檳榔子與ANE 30-100K所誘導的細胞凋亡與自體吞噬中之關聯性； b. 在已知的壓力訊號中比較檳榔子與ANE 30-100K可能誘導的訊號； c. 鑑定ANE 30-100K在細胞上（中）的接受器。 Areca nut (AN) is a popular but carcinogenic chewing material worldwide; however, studies of the cytotoxic effects of its ingredients on cells remain limited. We previously demonstrated that arecoline and AN extract (ANE) are capable of inducing apoptosis and autophagy, respectively. The autophagy-inducing activity in ANE was traced to the partially purified 30-100 kDa fraction (designated as ANE 30-100K). ANE 30-100K is composed of mainly carbohydrate and less than 2% proteins, and the autophagy-inducing activity is sensitive to either cellulase or proteinase K digestion, suggesting its identity to be a proteoglycan (or glycoprotein). These findings may provide new insights into the AN-associated pathology and serve as an ideal model for delineating the differences between the two distinct death pathways induced by AN components. Our recent results indicate that: (1) ANE 30-100K activates the AMP-activated protein kinase (AMPK), and Compound C inhibits the ANE 30-100K-induced autophagy; (2) both arecoline and ANE 30-100K stimulate ERK1/2 phosphorylation; (3) some unknown proteins from cell lysate were bound to ANE 30-100K-coated culture plate (their quantity are enough to be sequenced by our previous experiences). Therefore, the future works of this project include that: a. The involvement of calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMPK pathway in arecoline- and ANE 30-100K-mediated apoptosis and autophagy, respectively. b. Comparison of the known stress signals which are possibly transmitted by arecoline and ANE 30-100K. c. Identification of the cellular receptor of ANE 30-100K.