College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Department of Chemistry, College of Convergence and Integrated Science, Kyonggi University, Suwon 16627, Korea.
Int J Mol Sci. 2022 May 12;23(10):5397. doi: 10.3390/ijms23105397.
Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor involved in protection against initiation of carcinogenesis in normal cells. Notably, recent studies have demonstrated that aberrant activation of NRF2 accelerates the proliferation and progression of cancer cells. The differential effects of NRF2 on multi-stage carcinogenesis have raised a concern about the validity of NRF2 activators for chemoprevention. This prompted us to assess the effects of sulforaphane (SFN), a prototypic NRF2 activating chemopreventive phytochemical, on experimentally induced carcinogenesis. In the present study, SFN was daily injected intraperitoneally (25 mg/kg) for 3 months to male C57BL/6 mice at 6 months after single intraperitoneal administration of a hepatocarcinogen, diethylnitrosamine (DEN). The liver to body weight ratio, tumor growth, and the number and the size of hepatomas measured at 9 months after DEN administration were significantly higher in SFN-treated mice than those in vehicle-treated mice. Moreover, the expression of NRF2, its target protein NAD(P)H:quinone oxidoreductase 1, and the cell proliferation marker, proliferating cell nuclear antigen was further elevated in DEN plus SFN-treated mice. These results suggest that once hepatocarcinogenesis is initiated, SFN may stimulate tumor progression.
核因子红细胞 2 相关因子 2（NRF2）是一种关键的转录因子，参与正常细胞致癌作用的启动保护。值得注意的是，最近的研究表明，NRF2 的异常激活加速了癌细胞的增殖和进展。NRF2 对多阶段致癌作用的不同影响引起了人们对 NRF2 激活剂用于化学预防的有效性的关注。这促使我们评估了萝卜硫素（SFN）对实验诱导的致癌作用的影响。SFN 是一种典型的 NRF2 激活化学预防植物化学物质，在单次腹腔给予肝癌致癌物二乙基亚硝胺（DEN）后 6 个月，每天腹腔内注射（25mg/kg），持续 3 个月。与对照组相比，SFN 处理组的肝脏重量与体重比、肿瘤生长以及 DEN 给药后 9 个月时测量的肝癌数量和大小显著增加。此外，在 DEN 加 SFN 处理组中，NRF2、其靶蛋白 NAD（P）H：醌氧化还原酶 1 和细胞增殖标志物增殖细胞核抗原的表达进一步升高。这些结果表明，一旦肝癌发生，SFN 可能会刺激肿瘤进展。
