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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The pathological changes of parasympathetic nerves are considered as an independent prognostic factor of the survival rate for patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes, but little is known about the role of mAChR in hepatocytes and hepatic fibrosis and the signaling pathway of this receptor in regulation of hepatocytes remains elusive. Here, 3ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis in rats and the hepatocytes were isolated to investigate the expression of mAchR and the cell signaling pathways which were involved in. Compared with the normal state, the expression levels of m1, 3, 5 in fibrotic hepatocytes (FHC) and the cells treated with 10μM pilocarpine (Pi) were obviously increased, while decreased in m2,4. Pi could increase the value of alanine aminotransferase (ALT), hydroxyproline (Hyp), decrease albumin (ALB) and cell viability, while atropine could ameliorate fibrotic hepatocytes fuction. The p-AKT, p-ERK, p- JNK and p-P38 increased in Pi group or FHC group, but the inhibitors of PI3K, MAPK and PKC could reverse the Pi action and improve the FHC fuction. In this study we found that mAchR played an important role in the regulation of hepatic fibrosis process and the PKC, ERK, P38 and PI3K/AKT signaling pathways involved in the parasympathetic excitation mediated by mAchR., (Copyright © 2017. Published by Elsevier B.V.)