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Allyl-isothiocyanate against colorectal cancer via the mutual dependent regulation of p21 and Nrf2.
- Source :
-
European Journal of Pharmacology . Oct2023, Vol. 957, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00142999
- Volume :
- 957
- Database :
- Academic Search Index
- Journal :
- European Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 171989125
- Full Text :
- https://doi.org/10.1016/j.ejphar.2023.176016