探討海綿Hippospongia sp.天然物Rhopaloic acid對口腔癌細胞抗腫瘤及凋亡路徑之研究

Investigation of Antitumor and Apoptosis of Rhopaloic Acid Extracted from Sponge Hippospongia sp on Oral Cancer Cell

蔡文文(Tsai Wen-Wen)

指導教授 ： 徐睿良 ； 吳裕仁

國立屏東科技大學/農學院/生物科技系/碩士(2019年)

https://doi.org/10.6346/NPUST202000065

摘要

口腔癌為全球常見的十大惡性腫瘤，每年的病歷居高不下已成為全球重視之議題。然而口腔癌近九成以上好發於表皮黏膜細胞的鱗狀上皮細胞，生成的原因大多是長時間的慢性發炎至纖維化形成白斑或紅斑等等進階癌化，除了手術切除治療外等治療都有可能造成患者的痛苦或副作用，然而市面上已許多標靶單白質藥物，希望能安全且有效的治療口腔癌。 海綿富含的天然化合物在許多文獻及報導中都具有抗癌之潛力，因此本研究藉由海綿天然物Rhopaloic acid透過不同濃度測試並在相關實驗中得到驗證後，結果顯示在粒線體Bcl-2家族途徑與PI3K / AKT / mTOR訊息傳遞途徑中海綿天然物Rhopaloic acid確實能造成粒線體失活走向細胞凋亡並抑制口腔癌生長，進而說明了海綿天然物Rhopaloic acid在未來對於口腔癌治療上會是具有潛力的天然化合物。

關鍵字

口腔癌 ； 海綿 ； 海洋生物 ； 細胞凋亡 ； 粒線體

並列摘要

Oral cancer is one of the ten most common malignant tumors in the world, with a high prevalence. Nearly 90% of oral cancer occurs in mucosal epidermal cells. Most of the causes of formation are chronic inflammation to fibrosis to form white spots or advanced erythema. Except for surgical resection, target protein drugs are the primary treatment. Sponges are rich in active natural compounds, which showed potential anti-inflammatory and anti-cancer activities reported in previous reports. In this study, the natural product Rhopaloic acid isolated from sponge Hippospongia sp. was tested at different concentrations and evaluated its anti-cancer capability. The results indicated that it caused the oral cancer cells apoptosis via mitochondrial dysfunction by the inhibition of PI3K / AKT / mTOR signaling pathway. We believe that Rhopaloic acid has the potential for anti-oral cancer treatment.

並列關鍵字

Oral cancer ； sponge ； marine life ； apoptosis ； mitochondrion

參考文獻

Abdelmohsen, U. R., et al. (2017). "Potential of marine natural products against drug-resistant fungal, viral, and parasitic infections." The Lancet Infectious Diseases 17(2): e30-e41.

Allen, A. E. and J. W. Locasale (2018). "Glucose Metabolism in Cancer: The Saga of Pyruvate Kinase Continues." Cancer cell 33(3): 337-339.

Ashkenazi, A., et al. (2017). "From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors." Nature Reviews Drug Discovery 16(4): 273.

Benkendorff, K., et al. (2015). "Are the traditional medical uses of Muricidae molluscs substantiated by their pharmacological properties and bioactive compounds?" Marine drugs 13(8): 5237-5275.

Bibi, F., et al. (2017). "Bacteria from marine sponges: A source of new drugs." Current drug metabolism 18(1): 11-15.