烯丙基异硫氰酸酯（AITC）是一种常见的异硫氰酸酯（ITC），其化学预防和抗肿瘤作用被认为与NF-E2 p45相关因子2（Nrf2）的激活有关。然而，它对结直肠癌（CRC）的抗肿瘤作用尚不明确。在这里，我们研究了AITC对结直肠癌细胞株HCT116（人类）和MC38（小鼠）的治疗体外和/或体内效应及作用机制（MOA）。AITC的低浓度范围（体内1 mg/kg）处理显著抑制肿瘤细胞生长，并增加p21和Nrf2的表达。AITC介导的p21的诱导依赖于Nrf2，在低剂量下无关p53，在体外和体内均适用。相反，AITC的高剂量（体内5 mg/kg）未能增加充分水平的p21/MdmX，并损害了肿瘤的总抗氧化能力和随后的抗肿瘤效应。这些结果表明，AITC的适当剂量对于正确的Nrf2活化及其抗CRC效应非常重要和必需，从而提供了AITC在CRC预防和治疗中的潜在应用的见解。版权所有© 2023 Elsevier B.V.发表。

Allyl-isothiocyanate (AITC) is a common Isothiocyanates (ITC) and its chemo-preventive and anti-tumor effects are believed to be related to the activation of NF-E2 p45-related Factor 2 (Nrf2). However, its anti-tumor effects on colorectal cancer (CRC) are not well elucidated. Here, we investigated the therapeutic in vitro and/or in vivo effects and mechanisms of action (MOA) for AITC on CRC cell line HCT116 (human) and MC38 (mouse). AITC treatment in a low concentration range (1 mg/kg in vivo) significantly inhibited the tumor cell growth and increased the expression of p21 and Nrf2. The AITC-mediated induction of p21 was dependent on Nrf2 but independent on p53 in vitro and in vivo at low dose. In contrast, the high dose of AITC (5 mg/kg in vivo) failed to increase substantial levels of p21/MdmX, and impaired the total antioxidant capacity of tumors and subsequent anti-tumor effect in vivo. These results suggest that an optimal dose of AITC is important and required for the proper Nrf2 activation and its anti-CRC effects and thus, providing insights into the potential applications of AITC for the prevention and treatment of CRC.Copyright © 2023. Published by Elsevier B.V.