Abstract:
:Many natural phyto-products as perezone (Per) exhibit anti-cancer activities. Using experimental and computational studies, it was described that Poly ADP-ribose polymerase 1(PARP-1) inhibition and the induction of oxidative stress state explain the pro-apoptotic activity of Per. The aim of this study was to evaluate two phyto-products related to Per as anti-cancer agents: hydroxyperezone (OHPer) and its monoangelate (OHPer-MAng). These molecules were structurally characterized employing thermal analysis, IR spectrophotometry and X-ray diffraction techniques. The phyto-compounds evaluated in vitro in six cancer cell lines (K562, MCF-7, MDA-MB-231, HeLa, U373, A549) and non-malignant cells determinate their cytotoxicity, type of induced cell death, ability to avoid cell migration and changes at the redox status of the cell. Using, in vitro and computational studies provided the inhibition of PARP-1 and its potential binding mode. Cell proliferation assays demonstrated that OHPer-MAng treatment significantly induces apoptosis in triple negative breast cancer (TNBC) cell line (MDA-MB-231 IC50 = 3.53 μM), being particularly less cytotoxic to Vero cells (IC50 = 313.92 μM), human lymphocytes (IC50 = 221.46 μM) and rat endothelial cells (IC50=> 400 μM). The treatment of MDA-MB-231 cells with OHPer-MAng showed inhibition of migration by cancer cells. The induction of an oxidative stress state, similar to other quinones and PARP-1 inhibition explains the pro-apoptotic activity of OHPer-MAng. Docking studies showed that OHPer-MAng establishes great non-bonding interactions with the lateral chains of Tyr235, Hys201, Tyr246, Ser203, Asn207, and Gly233 located at the catalytic site of PARP-1, also demonstrating the anti-cancer activity of OHPer-MAng in TNBC cell line.
journal_name
Biochimiejournal_title
Biochimieauthors
Hernández-Rodríguez M,Mendoza Sánchez PI,Macías Perez ME,Cruz ER,Jiménez EM,Aceves-Hernández JM,Nicolás-Vázquez MI,Ruvalcaba RMdoi
10.1016/j.biochi.2020.03.003subject
Has Abstractpub_date
2020-01-01 00:00:00pages
158-169eissn
0300-9084issn
1638-6183pii
S0300-9084(20)30048-1journal_volume
171-172pub_type
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