Abstract | BACKGROUND: The discovery of novel derivative of berberine (BBR) having higher anti- tumor activity in vivo is of clinical importance. In this profile, 13-[CH2CO-Cys-(Bzl)-OBzl]- berberine (13-Cys-BBR) was prepared for related assays. PURPOSE: The object of preparation and evaluation is to show the advantages of 13-Cys-BBR over BBR in both in vitro and in vivo anti- tumor actions, furthermore to correlate the proliferation of cancer cells with ROS formation and anti-apoptosis protein (XIAP) expression inside cancer cells. METHODS: Transwell chamber was used to simulate the intestinal and cell wall for bioavailability evaluation; MTT assay was used to evaluate the in vitro anti-proliferation activity; fluorescein isothiocyanate content was used to represent ROS level in HCT-8 cells; Western blot assay was used to quantify the expression of XIAP, caspase-3, and poly ADP-ribose polymerase in HCT-8 cells; and S180 mouse model was used to evaluate the in vivo anti- tumor activity. RESULTS: In vitro the IC50 values (~15-40 μM) of 13-Cys-BBR against the proliferation of eight cancer cell lines were significantly lower than those of BBR (~25-140 μM); the content of ROS formed inside HCT-8 cells treated by 13-Cys-BBR was ~3.44-folds higher than that inside HCT-8 cells treated by BBR; the expression of XIAP in HCT-8 cells treated by 13-Cys-BBR was ~1.21-folds lower than that in HCT-8 cells treated by BBR; the tumor weight of S180 mice orally treated by 2 μmol/kg/day of 13-Cys-BBR (~1.5 g) was significantly lower than that of S180 mice orally treated by 2 μmol/kg/day of BBR (~2.5 g); and the active pocket of XIAP was more suitable for 13-Cys-BBR than for BBR. CONCLUSION: The anti- tumor action correlates with ROS and apoptosis protein, which suggests 13-Cys-BBR is a promising candidate for preclinical study.
|
Authors | Guanyu Li, Yi Ren, Xiaoyi Zhang, Shurui Zhao, Yaonan Wang, Jianhui Wu, Shiqi Peng, Ming Zhao |
Journal | OncoTargets and therapy
(Onco Targets Ther)
Vol. 12
Pg. 10651-10662
( 2019)
ISSN: 1178-6930 [Print] New Zealand |
PMID | 31824172
(Publication Type: Journal Article)
|
Copyright | © 2019 Li et al. |