紫外線會對皮膚造成傷害，包括:產生紅斑、DNA斷裂及皮膚癌等。許多研究中證實鳳梨葉萃取物具有降血糖及降血脂之功效；查耳酮其衍生物於藥理活性上具抗發炎、抑制血栓形成、抗氧化及抑制腫瘤細胞生長之活性。 本篇論文中，選用受精後72小時斑馬魚之幼魚為快篩模式物種，評估鳳梨葉萃取物和查耳酮其衍生物對是否具有防護紫外線照射能力。進一步探討是否能夠有效增強UVB於人類表皮癌細胞(A431)所引起之細胞凋亡。 由研究結果得知，鳳梨葉萃取物及查耳酮衍生物皆能夠有效減少UVB照射後所產生之ROS含量及具有防護魚鰭損傷功效。UVB、鳳梨葉萃取物和查耳酮及其衍生物分別作用於A431細胞時，都能夠抑制癌細胞生長。然而，UVB (30 mJ/cm2)與Compound 4 (10 μg/mL)合併與各別作用A431細胞後，發現合併治療之PARP片段(PARP cleavage)表現量增加，即表示合併治療誘導之細胞凋亡情形更加顯著。UVB和Compound 4合併作用於人類表皮膚癌細胞(A431)具有協同作用，因此，Compound 4可能為一種治療皮膚癌之化療藥物。 本研究以斑馬魚之幼魚作為模式物種，添加抗氧化物質評估是否具有防護UVB之效果。此模式的建立，之後可以用於快速檢驗抗氧化物質的光防護能力，並且同時評估抗氧化物質於生物體內之毒性影響。另外，藉由與UVB合併治療A431細胞，探討抗氧化物質是否具有開發為抗癌及化療藥物的潛力。此研究模式之建立，能夠作為日後快速評估防護UVB照射能力與治療皮膚癌之化療藥物開發。 Human exposed to heavy UVR could cause serious health effects such as skin erythema, DNA breakage and skin cancers. It is reported that chalcone have various biological activities such as anti-inflammatory, anti-oxidative, anti-cancer, and anti-coagulant effects. The extract of pineapple leaves has anti-diabetic and anti-dyslipidemic effects. This study is aimed to focus on those antioxidants applied in 3 day-post-fertilization (dpf) zebrafish model system to evaluate whether providing the UV protective effects. Here, we investigated whether pineapple leaf extract and chalcone derivatives can sensitize A431 human epidermoid carcinoma cells to UVB induced cell death. We examined the combined effect of UVB and drug on A431 cells. Results showed the extract of pineapple leaves and chalcone derivatives can protect zebrafish fin from UVB damage and reduce of reactive oxygen species (ROS) produce. Exposure of A431 carcinoma cells to UVB radiation, pineapple leaves and chalcone derivatives can induced cytotoxicity. However, the combination of Compound 4 (10 μg/mL) and UVB (30 mJ/cm2) exposure was associated with increased cytotoxicity inhibition of A431 cells compared with either agent alone. Moreover, Compound 4 markedly activation the PARP cleavage in protein expression, and finally cell death. In conclusion, our study demonstrates that the combination of Compound 4 and UVB act synergistically against skin cancer cells. Thus, Compound 4 is a potential chemotherapeutic agent against skin carcinogenesis. In the future, UVB protective effects and speedy antioxidants selection could be applied in these model systems. These screening method are excellent and effective for large-scale organisms toxicity and antioxidants screening. In conclusion, our study demonstrates that the combination of antioxidants and UVB act synergistically against skin cancer cells. Thus, chalcone derivatives and similar antioxidants is a potential chemotherapeutic agent against skin carcinogenesis.
