Zou Zhiyuan V, Le Gal Kristell, El Zowalaty Ahmed E, Pehlivanoglu Lara E, Garellick Viktor, Gul Nadia, Ibrahim Mohamed X, Bergh Per-Olof, Henricsson Marcus, Wiel Clotilde, Akyürek Levent M, Bergo Martin O, Sayin Volkan I, Lindahl Per
Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, 405 30 Gothenburg, Sweden.
Antioxidants (Basel). 2021 Feb 4;10(2):241. doi: 10.3390/antiox10020241.
Dietary antioxidants and supplements are widely used to protect against cancer, even though it is now clear that antioxidants can promote tumor progression by helping cancer cells to overcome barriers of oxidative stress. Although recent studies have, in great detail, explored the role of antioxidants in lung and skin tumors driven by RAS and RAF mutations, little is known about the impact of antioxidant supplementation on other cancers, including Wnt-driven tumors originating from the gut. Here, we show that supplementation with the antioxidants N-acetylcysteine (NAC) and vitamin E promotes intestinal tumor progression in the ApcMin mouse model for familial adenomatous polyposis, a hereditary form of colorectal cancer, driven by Wnt signaling. Both antioxidants increased tumor size in early neoplasias and tumor grades in more advanced lesions without any impact on tumor initiation. Importantly, NAC treatment accelerated tumor progression at plasma concentrations comparable to those obtained in human subjects after prescription doses of the drug. These results demonstrate that antioxidants play an important role in the progression of intestinal tumors, which may have implications for patients with or predisposed to colorectal cancer.
膳食抗氧化剂和补充剂被广泛用于预防癌症，尽管现在已经清楚抗氧化剂可以通过帮助癌细胞克服氧化应激障碍来促进肿瘤进展。尽管最近的研究已经非常详细地探讨了抗氧化剂在由RAS和RAF突变驱动的肺癌和皮肤肿瘤中的作用，但对于抗氧化剂补充对其他癌症的影响却知之甚少，包括源自肠道的Wnt驱动的肿瘤。在这里，我们表明，在家族性腺瘤性息肉病（一种遗传性结直肠癌）的ApcMin小鼠模型中，补充抗氧化剂N-乙酰半胱氨酸（NAC）和维生素E会促进肠道肿瘤进展，该模型由Wnt信号驱动。两种抗氧化剂都增加了早期肿瘤的大小和更晚期病变的肿瘤分级，而对肿瘤起始没有任何影响。重要的是，NAC治疗在血浆浓度与人类受试者服用处方剂量药物后获得的浓度相当的情况下加速了肿瘤进展。这些结果表明，抗氧化剂在肠道肿瘤进展中起重要作用，这可能对患有结直肠癌或易患结直肠癌的患者有影响。
