PURPOSE: Our previous proteomics analysis revealed that treatment with PA resulted in the upregulation of an autophagy marker, LC3B in melanoma cells. Therefore, the present study sought to investigate the role of PA-induced autophagy in melanoma cells.
METHODS: Transmission electron microscopy was performed for examination of autophagic ultra-structures in PA-treated A375 cells. Cytoplasmic LC3B and p62/SQSMT1 punctate structures were detected using immunofluorescene staining. Expression levels of LC3B II, p62/SQSMT1, ATG 12, Beclin 1, phospho S6 (ser235/236), phospho AMPK (Thr172) and cleaved PARP were evaluated by western blotting.
RESULTS: Autophagosomes, autolysosomes and punctuates of LC3 proteins could be observed in PA-treated A375 cells. PA-induced autophagy in A375 melanoma cells was found to be mediated through the inhibition of mTOR signaling and activation of AMPK pathway. Furthermore, we showed that PA-induced apoptosis was increased in the presence of an autophagy inhibitor, signifying the cytoprotective effect of PA-induced autophagy in melanoma cells.
CONCLUSION: Taken together, results from the present study suggest that the inhibition of autophagy by targeting mTOR and AMPK could potentiate the cytotoxicity effects of PA on melanoma cells.
AIM: We want to demonstrate that the antioxidant properties of Swietenia macrophylla ethanol extract nanoparticles can prevent kidney cell damage brought on by streptozotocin (STZ) in the current investigation.
METHODS: This study employs high-energy ball milling to produce nanoparticles from S. macrophylla extract. Additionally, dynamic light scattering (DLS) is utilized to characterize the nanoparticle sizes of the S. macrophylla ethanol extract. Five groups, each consisting of 8 rats, were formed from 40 rats. Control rats received distilled water, the diabetic rats were administered STZ injections, while S. macrophylla rats were given S. macrophylla extract nanoparticles orally and STZ injection. After the trial, blood from a rat was drawn intracardially to check the levels of blood urea nitrogen (BUN) and creatinine. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were then assessed in kidney tissue samples. Histological alterations were evaluated in kidney section samples.
RESULTS: A DLS analysis estimated the size of the S. macrophylla ethanol extract nanoparticles to be about 91.50 ± 23.06 nm. BUN and creatinine levels were significantly raised after STZ treatment. STZ significantly decreased SOD and GPx levels in kidney tissue while raising MDA levels (p < 0.05). Swietenia macrophylla ethanol extract nanoparticle caused the decreased levels of BUN and creatinine in blood to normal levels (p < 0.05), indicating that S. macrophylla ethanol extract prevented the STZ-induced kidney cell damage. Additionally, S. macrophylla nanoparticles significantly raise GPx and SOD levels in kidney tissue while lowering MDA levels (p < 0.05). These actions are thought to have prevented kidney histological alterations (degeneration and necrosis) in diabetic rats.
CONCLUSION: According to these results, the anti-oxidative stress properties of S. macrophylla nanoparticles make them potentially effective nephroprotective therapies for STZ-induced kidney cell damage.