Candesartan and valsartan Zn() complexes as inducing agents of reductive stress: mitochondrial dysfunction and apoptosis
Cellular oxidative stress is considered an inducer of carcinogenesis but the association of reactive oxygen species (ROS) with cancer is sometimes contradictory. The antihypertensive drugs candesartan and valsartan were reported to behave as antioxidant agents. In the present study, we prepared thei...
Saved in:
Published in | New journal of chemistry Vol. 45; no. 2; pp. 939 - 951 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Cambridge
Royal Society of Chemistry
18.01.2021
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Cellular oxidative stress is considered an inducer of carcinogenesis but the association of reactive oxygen species (ROS) with cancer is sometimes contradictory. The antihypertensive drugs candesartan and valsartan were reported to behave as antioxidant agents. In the present study, we prepared their Zn(
ii
) coordination complexes, [ZnCand(H
2
O)
2
]·2H
2
O (ZnCand) and [ZnVals(H
2
O)
2
] (ZnVals), and determined that they also depleted ROS by the induction of a reductive state in response to glutathione (GSH) generation and decreased lung cancer cell viability (IC
50
= 175 and 220 µM, respectively), while being non-cytotoxic for normal lung fibroblasts (MRC5). The Zn complexes affected the mitochondria membrane, increased the pro- and anti-apoptotic protein ratio, Bax/Bcl-XL, and caspase-9 activation, by late apoptosis. Their co-incubation with
N
-acetylcysteine (NAC) exacerbated ROS reduction and increased cell death, whereas the H
2
O
2
co-treatment restored the ROS values and normal cell growth. These data suggest that the excess reducing equivalents and low levels of ROS are also critical for the functioning of A549 cells.
Candesartan and valsartan Zn(
ii
) complexes as inducing agents of reductive stress, including mitochondrial dysfunction and apoptosis. |
---|---|
Bibliography: | 1 Fig. S1: Representative fluorescence microscopy images of cells at different stages. Magnification 40×. Live cells (L), early apoptosis (EA), late apoptosis (LA), and necrosis (N). See DOI Electronic supplementary information (ESI) available: Table S1: Assignment of the main vibrational frequencies of candesartan (Cand) and ZnCand; wavenumbers are in cm 10.1039/d0nj02937h Table S2: Assignment of the main vibrational frequencies of valsartan (Vals) and ZnVals; wavenumbers are in cm |
ISSN: | 1144-0546 1369-9261 |
DOI: | 10.1039/d0nj02937h |