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五种不同褐藻来源的多酚具有多种功效、分子靶点和作用模式：来自海洋的抗胰腺癌研究成果。

Anti-pancreatic cancer deliverables from sea: first-hand evidence on the efficacy, molecular targets and mode of action for multifarious polyphenols from five different brown-algae.

机构信息

Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.

出版信息

PLoS One. 2013 Apr 16;8(4):e61977. doi: 10.1371/journal.pone.0061977. Print 2013.

DOI:10.1371/journal.pone.0061977
PMID:23613993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3628576/
Abstract

Pancreatic cancer (PC) remains the fourth leading cause of cancer death with an unacceptable survival that has remained relatively unchanged over the past 25 years. The presence of occult or clinical metastases at the time of diagnosis together with the lack of effective chemotherapies pose a dire need for designing new and targeted therapeutic deliverables that favors the clinical outcome. Herein, we investigated the anti-tumorigenic potential of polyphenols from five different brown-algae in human PC cells (MiaPaCa-2, Panc-1, BXPC-3 and Panc-3.27). Total anti-oxidant capacity (TAC) analysis on stepwise polyphenol separations with increasing polarity (Hexane-DCM-EA-methanol) identified high levels of TAC in DCM and EA extractions across all seaweeds assessed. All DCM and EA separated polyphenols induced a dose-dependent and sustained (time-independent) inhibition of cell proliferation and viability. Further, these polyphenols profoundly enhanced DNA damage (acridine orange/Ethidium bromide staining and DNA fragmentation) in all the cell lines investigated. More importantly, luciferase reporter assay revealed a significant inhibition of NFκB transcription in cells treated with polyphenols. Interestingly, QPCR analysis identified a differential yet definite regulation of pro-tumorigenic EGFR, VEGFA, AKT, hTERT, kRas, Bcl2, FGFα and PDGFα transcription in cells treated with DCM and EA polyphenols. Immunoblotting validates the inhibitory potential of seaweed polyphenols in EGFR phosphorylation, kRas, AurKβ and Stat3. Together, these data suggest that intermediate polarity based fractions of seaweed polyphenols may significantly potentiate tumor cell killing and may serve as potential drug deliverable for PC cure. More Studies dissecting out the active constituents in potent fractions, mechanisms of action and synergism, if any, are warranted and are currently in process.

摘要

胰腺癌（PC）仍然是第四大癌症死亡原因，过去 25 年来，其生存率一直保持不变，令人难以接受。在诊断时存在隐匿性或临床转移，加上缺乏有效的化疗，这就迫切需要设计新的靶向治疗药物，以改善临床结果。在此，我们研究了五种不同褐藻中的多酚对人胰腺癌细胞（MiaPaCa-2、Panc-1、BXPC-3 和 Panc-3.27）的抗肿瘤潜力。对不同极性（正己烷-DCM-EA-甲醇）的多酚分步分离的总抗氧化能力（TAC）分析表明，在所评估的所有海藻中，DCM 和 EA 提取物均具有高水平的 TAC。所有 DCM 和 EA 分离的多酚均诱导剂量依赖性和持续（时间独立）的细胞增殖和活力抑制。此外，这些多酚在所有研究的细胞系中显著增强了 DNA 损伤（吖啶橙/溴化乙锭染色和 DNA 片段化）。更重要的是，荧光素酶报告基因检测显示，用多酚处理的细胞中 NFκB 转录受到显著抑制。有趣的是，QPCR 分析确定了用 DCM 和 EA 多酚处理的细胞中促肿瘤 EGFR、VEGFA、AKT、hTERT、kRas、Bcl2、FGFα和 PDGFα转录的差异但明确的调节。免疫印迹验证了海藻多酚在 EGFR 磷酸化、kRas、AurKβ和 Stat3 抑制方面的潜力。总之，这些数据表明，基于中间极性的海藻多酚可能显著增强肿瘤细胞杀伤作用，并可作为 PC 治疗的潜在药物输送载体。目前正在进行更多的研究，以分离有效成分、作用机制和协同作用，如果有的话。

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