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Effects of 2-aryl-1-cyano-1,2,3,4-tetrohydroisoquinolines on apoptosis induction mechanism in NB4 and MKN-45 cells.
- Source :
-
Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2019 Feb; Vol. 54, pp. 295-303. Date of Electronic Publication: 2018 Oct 17. - Publication Year :
- 2019
-
Abstract
- Our previous study found that 2-aryl-1-cyano-1,2,3,4-tetrahydroisoquinolines (CATHIQs) have excellent anti-cancer activity and obvious apoptosis induction phenomenon. As our continuing research, this study further explored their underlying molecular mechanism of apoptosis induction in cancer cells. Flow cytometry analysis showed that the NB4 cells treated by 1-cyano-2-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline or the MKN-45 cells treated by 1-cyano-2-(4-trifluoromethylphenyl)-1,2,3,4-tetrahydroisoquinoline for 48 h were at early stage of apoptosis, and the cell cycle arrest was only slightly affected. Apoptosis rates of the cells significantly increase with the treatment concentration of the compounds. The compounds could significantly decrease the activities of SOD, raise the MDA level and promote the LDH leakage, suggesting that the excessive formation of ROS should be involved in the cell apoptosis. Western blot analysis showed that the compounds improved both Bax/Bcl-2 ratio and cleavages of procaspase-3, promoted efflux of cytochrome c to cytosol and phosphorylation of p38 and JNK, and attenuated phosphorylations of Akt and ERK. Together, inhibitions of PI3K/Akt and ERK and activation of p38 mediated the compounds-induced apoptosis through modulating the mitochondrial pathway and/or ROS production.<br /> (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Subjects :
- Apoptosis drug effects
Apoptosis Regulatory Proteins metabolism
Cell Line, Tumor
Humans
L-Lactate Dehydrogenase metabolism
Malondialdehyde metabolism
Mitochondria drug effects
Mitochondria metabolism
Phosphotransferases metabolism
Superoxide Dismutase metabolism
Antineoplastic Agents pharmacology
Tetrahydroisoquinolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3177
- Volume :
- 54
- Database :
- MEDLINE
- Journal :
- Toxicology in vitro : an international journal published in association with BIBRA
- Publication Type :
- Academic Journal
- Accession number :
- 30342220
- Full Text :
- https://doi.org/10.1016/j.tiv.2018.10.007