Stadlbauer Sven, Steinborn Carmen, Klemd Amy, Hattori Fumihiko, Ohmori Ken, Suzuki Keisuke, Huber Roman, Wolf Philipp, Gründemann Carsten
Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo, Japan.
Planta Med. 2018 Jul;84(11):813-819. doi: 10.1055/s-0044-102099. Epub 2018 Feb 21.
Among the known or suspected risk factors, inflammation plays an important role in infectious and non-infectious pathways leading to cancer. Green tea polyphenols have been associated with reducing inflammation and protection against carcinogenesis, especially in prostate cancer. While most of the research in this field, so far, has focussed on epigallocatechin-3--gallate only, we studied epicatechin-3--gallate, the second most abundant green tea polyphenol with essential therapeutic potential, to obtain a more detailed understanding of its anti-tumor and anti-inflammatory action. Furthermore, to improve the bioactivity of (-)-epicatechin-3--gallate, we synthesized a difluoro analogue, called (-)-5,7-difluoro-epicatechin-3--gallate. Both compounds reduced cell proliferation of human primary inflammatory lymphocytes in an apoptosis-specific fashion, while (-)-5,7-difluoro-epicatechin-3--gallate had a significantly higher activity compared to the natural product (-)-epicatechin-3--gallate. Treatment of low-metastatic LNCaP and high-metastatic PC-3 prostate cancer cells with (-)-epicatechin-3--gallate and (-)-5,7-difluoro-epicatechin-3--gallate demonstrated a dose-dependent inhibition of cell viability in the low micromolar range. These effects suggest that (-)-epicatechin-3--gallate and the more effective (-)-5,7-difluoro-epicatechin-3--gallate could be therapeutically used to inhibit tumorigenesis during initiation, promotion, and progression by diminishing the amount of inflammation due to a reduction of inflammatory lymphocytes. Further studies are needed to prove this in experiments.
在已知或疑似的风险因素中，炎症在导致癌症的感染性和非感染性途径中起着重要作用。绿茶多酚与减轻炎症和预防癌症发生有关，尤其是在前列腺癌方面。虽然该领域目前的大多数研究仅聚焦于表没食子儿茶素-3-没食子酸酯，但我们研究了表儿茶素-3-没食子酸酯，这是含量第二丰富且具有重要治疗潜力的绿茶多酚，以更详细地了解其抗肿瘤和抗炎作用。此外，为了提高（-）-表儿茶素-3-没食子酸酯的生物活性，我们合成了一种二氟类似物，即（-）-5,7-二氟表儿茶素-3-没食子酸酯。两种化合物均以凋亡特异性方式降低人原发性炎性淋巴细胞的细胞增殖，而（-）-5,7-二氟表儿茶素-3-没食子酸酯与天然产物（-）-表儿茶素-3-没食子酸酯相比具有显著更高的活性。用（-）-表儿茶素-3-没食子酸酯和（-）-5,7-二氟表儿茶素-3-没食子酸酯处理低转移性LNCaP和高转移性PC-3前列腺癌细胞，在低微摩尔范围内显示出剂量依赖性的细胞活力抑制作用。这些结果表明，（-）-表儿茶素-3-没食子酸酯和更有效的（-）-5,7-二氟表儿茶素-3-没食子酸酯可通过减少炎性淋巴细胞数量从而减轻炎症程度，在肿瘤发生的起始、促进和进展阶段用于抑制肿瘤发生。需要进一步的研究在实验中证实这一点。
