PO.CH01.05 · 化学
利用海马齿（Carpobrotus edulis）甲醇提取物靶向凋亡机制以抑制胰腺癌生长
Targeting apoptotic machinery using methanolic extracts of Carpobrotus edulis to suppress pancreatic cancer growth
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摘要 Abstract
中文摘要
胰腺癌仍然是一项艰巨的全球健康挑战。当前的癌症治疗方法，如化疗，费用高昂且疗效有限。因此，研究替代性抗癌治疗方法（如药用植物）至关重要。本研究旨在通过靶向胰腺癌细胞（MIA PaCa2）的凋亡机制，探讨海马齿（Carpobrotus edulis）粗甲醇提取物及分离化合物的潜在抗癌特性。本研究开展了多种检测，包括 Alamar blue、ATP、Hoechst 染色、Caspase 3/7 活性、DNA 片段化和 RT-qPCR，以评估凋亡诱导情况。粗甲醇提取物及分离化合物对非癌性细胞系 MRC-5 无影响。机制研究证实，粗提取物激活了外源性 TNF 介导的凋亡通路，其证据为 TNF 表达和 caspase 3/7 活性显著升高，从而导致 DNA 和细胞核片段化、染色质浓缩以及凋亡小体形成。细胞汇合度的丧失，加之 STAT3 的非显著（p>0.05）下调，进一步提示细胞生长受到抑制。虽然在粗提取物和分离化合物中均观察到 p53、Bak1 和 Fas 表达的某些变化，但这些变化均无统计学意义（p>0.05）。对所鉴定的 7,9-二叔丁基-氧杂螺[4.5]癸-6,9-二烯-2,8-二酮和 1-十八醇进行的蛋白-配体对接研究证实，这些化合物对选定的配体（TNFR、FADD、p53、Bak1 和 STAT3）具有高亲和力。未来的研究将着重于对活性最强的分离化合物进行进一步纯化和研究。
查看英文原文 English abstract
Pancreatic cancer remains a formidable global health challenge. Current cancer treatments, such as chemotherapy are expensive and limited. Consequently, investigating alternative anticancer treatments, such as medicinal plants, is crucial. This study aimed to investigate the potential anticancer properties of a crude methanolic extract and isolated compounds from Carpobrotus edulis by targeting apoptotic machinery in pancreatic cancer cells (MIA PaCa2). Multiple assays, including Alamar blue, ATP, Hoechst staining, Caspase 3/7 activity, DNA fragmentation, and RT-qPCR, were conducted to assess apoptosis induction. The crude methanol and isolated compounds did not affect the MRC-5 non-cancerous cell line. Mechanistic investigations confirmed that the crude extract activated the extrinsic TNF-mediated apoptosis pathway, evidenced by a significant increase in TNF expression and caspase 3/7 activity, leading to DNA and nuclear fragmentation, chromatin condensation, and the formation of apoptotic bodies. The loss of cell confluence, supported by non-significant( p >0,05) downregulation of STAT3, further suggested inhibited cell growth. While some changes were observed in the expression of p53, Bak1, and Fas for both the crude extract and isolated compounds, these were not statistically significant ( p >0,05). Protein-ligand docking studies of the identified 7,9-Ditert-butyl-oxaspiro [4.5] deca-6,9-diene-2,8-dione and 1-octadecanol proved the compounds as having high affinity for the selected ligands: TNFR, FADD, p53, Bak1, and STAT3. Future research will focus on the further purification and investigation of the most potent isolated compound.
利益披露 Disclosure
L. Motadi, None..
R. Makalapetlo, None.