| Abstract: | 自古以來，植物萃取物就被用於疾病的治療，即使是醫學發達的今日也不例外，例如萃取自薑黃(Curcuma longa)根莖的薑黃素(Curcumin)其具有抗癌、抗發炎以及抗氧化的能力，對許多癌症的治療很有效，但其不穩定性以及生物利用度差，導致臨床應用受到限制。因此為了改善活性及改變藥物性質，已經合成了幾種結構相關的化合物並評估為抗增殖和抗感染藥物，其中4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid]又稱為CLEFMA為新型的薑黃類似物，近年來有文獻指出CLEFMA對肺腺癌細胞具有抗增殖能力，並誘導癌細胞走向死亡。然而，CLEFMA在骨肉瘤中對於腫瘤的效果以及所涉及的分子機制仍未被深入探討。在本篇研究中，我們發現CLEFMA可以降低人類骨肉瘤細胞的存活率，並以流式細胞儀分析DNA含量的分布情形，結果顯示隨著CLEFMA濃度的增加於24小時後S checkpoint調控蛋白表達受到抑制，造成細胞週期停滯在S phase而引起細胞凋亡。在機制方面，我們發現CLEFMA活化了caspase 8、caspase 9和caspase 3等細胞凋亡調控蛋白，而造成細胞凋亡的發生。此外，CLEFMA還可以活化MAPK路徑蛋白JNK、p38，進而誘導細胞凋亡。綜合以上結果，我們證實CLEFMA對於人類骨肉瘤細胞有作用，可以抑制細胞生長並誘導細胞凋亡。未來或許可提供骨癌患者新的治療選擇。
Since ancient times, plant extracts have been used in the treatment of diseases, even today, when medicine is developed. For example, curcumin extracted from the rhizome of Curcuma longa has anti-cancer, anti-inflammatory and anti-oxidant properties and is effective for the treatment of many cancers. However, its instability and poor bioavailability lead to limited clinical applications. Therefore, in order to improve the activity and to change the properties of the drug, several structurally related compounds have been synthesized and evaluated as anti-proliferative and anti-infective drugs. Among them, 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] is also known as CLEFMA as a novel turmeric analog. In recent years, it has been reported that CLEFMA has anti-proliferative ability to lung adenocarcinoma cells and induces cancer cells to die. However, the effect of CLEFMA on tumors in osteosarcoma and the molecular mechanisms involved have not been explored in depth. In this study, we found that CLEFMA can reduce the survival rate of human osteosarcoma cells. The distribution of DNA content was analyzed by flow cytometry. The results showed that with the increase of CLEFMA concentration, the expression of S checkpoint regulated protein was inhibited after 24 hours, which caused the cell cycle to arrest in S phase and cause apoptosis. In terms of mechanism, we found that CLEFMA activates apoptosis regulatory proteins such as caspase 8, caspase 9, and caspase 3, leading to apoptosis. In addition, CLEFMA can also activate MAPK pathway proteins JNK, p38, and then induce apoptosis. Based on the above results, we confirmed that CLEFMA has an effect on human osteosarcoma cells, which can inhibit cell growth and induce apoptosis. In the future, it may be possible to offer new treatment options for patients with bone cancer. |
