bims-aporos 2018-07-22 papers

Issue of 2018‒07‒22
four papers selected by
Gavin McStay
Staffordshire University

Eur Spine J. 2018 Jul 14.

Lupeol against high-glucose-induced apoptosis via enhancing the anti-oxidative stress in rabbit nucleus pulposus cells.

Ming-Bo Guo, De-Chun Wang, Hai-Fei Liu, Long-Wei Chen, Jian-Wei Wei, Yong Lin, Hui Xue.

PURPOSE: This study aimed to investigate the potential mechanism and value of lupeol in inhibiting high-glucose-induced apoptosis in rabbit nucleus pulposus cells (NPCs).METHODS: NPCs were divided into four groups: control (CON), high glucose (HG), LUP, and HG + LUP. Viability, reactive oxygen species (ROS) levels, and apoptosis were examined in NPCs. The protein expression levels of Bax, Bcl-2, cytochrome C, and caspase 9/3 were measured using reverse transcription-polymerase chain reaction and Western blot assay.
RESULTS: The apoptotic rate and total ROS level of the HG group significantly increased compared with the CON group (P < 0.01). The total ROS level in the HG + LUP group significantly decreased compared with the HG group(P < 0.05). The mRNA expression of Bcl-2 was significantly upregulated, whereas the expression of Bax, cytochrome C, and caspase 9/3 was downregulated in the HG + LUP group compared with those in the HG group(P < 0.05).The Western blot assay showed that the expression of Bcl-2 was upregulated, but the expression of Bax, cytochrome C, and caspase 9/3 was significantly downregulated in the HG + LUP group compared with the HG group (P < 0.05).
CONCLUSIONS: Lupeol inhibited high-glucose-induced apoptosis in NPCs by enhancing the anti-oxidative stress in the mitochondria. This study suggested lupeol as a potential therapeutic drug for treating intervertebral disc degeneration under hyperglycaemic conditions. These slides can be retrieved under Electronic Supplementary Material.

Keywords: Anti-oxidative stress; Apoptosis; Intervertebral disc degeneration; Lupeol; Nucleus pulposus

DOI: https://doi.org/10.1007/s00586-018-5687-9

Int J Med Sci. 2018 ;15(8): 771-781

The replicative senescent mesenchymal stem / stromal cells defect in DNA damage response and anti-oxidative capacity.

Jin Yu, Jiazhong Shi, Yue Zhang, Yi Zhang, Yaqin Huang, Zhiwen Chen, Jin Yang.

Replicative senescence and potential malignant transformation are great limitations in the clinical application of bone marrow-derived mesenchymal stem / stromal cells (MSCs). An abnormal DNA damage response may result in genomic instability, which is an integral component of aging and tumorigenesis. However, the effect of aging on the DNA damage response in MSCs is currently unknown. In the present study, we evaluated the DNA damage response induced by oxidative stress and DNA double-strand breaks in human bone marrow-derived MSCs. After long-term cell culture, replicative senescent MSCs (sMSCs) were characterized by a poor proliferation rate, high senescence-associated β-galactosidase activity, and enhanced expression of P53 and P16. Features of the DNA damage response in these sMSCs were then compared with those from early-passage MSCs. The sMSCs were more sensitive to hydrogen peroxide and bleomycin treatment with respect to cell viability and apoptosis induction. Combined with the comet assay, γH2AX foci characterization and reactive oxygen species detection were used to demonstrate that the antioxidant and DNA repair ability of sMSCs are attenuated. This result could be explained, at least in part, by the downregulation of anti-oxidation and DNA repair genes, including Cu/Zn-SOD, GPX, CAT, OGG1, XRCC1, Ku70, BRCA2 and XRCC4. In conclusion, MSCs aging is associated with a reduction in the DNA repair and anti-oxidative capacity.

Keywords: DNA damage response; DNA double-strand breaks; Replicative senescence; mesenchymal stem cells; oxidative stress

DOI: https://doi.org/10.7150/ijms.24635

Cell Physiol Biochem. 2018 Jul 13. 48(1): 208-214

Apocynin Attenuates Cobalt Chloride-Induced Pheochromocytoma Cell Apoptosis by Inhibiting P38-MAPK/Caspase-3 Pathway.

Jie Liu, Yuzhang Zhu, Shipiao Chen, Bin Shen, Fang Yu, Yi Zhang, Ruilin Shen.

BACKGROUND/AIMS: Apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been identified as a potential neuroprotectant. In this study, we aimed to investigate the protective effect of apocynin against cobalt chloride (CoCl2)-induced pheochromocytoma (PC12) cell apoptosis.METHODS: The PC12 cell culture was pretreated with apocynin and/or SB203580 (p38 mitogen-activated protein kinase [p38-MAPK] inhibitor) at different time points prior to CoCl2 incubation. The cell viability, apoptosis rate, DAN damage, and antioxidant activity were detected using cell counting kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), and comet assay respectively. The protein and mRNA expressions of p38-MAPK and caspase-3 in the cells were measured by qRT-PCR and Western blotting.
RESULTS: Apocynin inhibited CoCl2-mediated apoptosis, reduced oxidative stress, and down-regulated the expression of p38-MAPK and caspase-3.
CONCLUSIONS: Our findings show that apocynin attenuated CoCl2-induced apoptosis by potently restraining p38-MAPK-caspase-3 signaling pathway in PC12 cells, suggesting that apocynin may be a potent prophylactic reagent against CoCl2-mediated PC12 cell apoptosis.

Keywords: Apocynin; Apoptosis; Caspase-3; Cobalt chloride; NADPH oxidase; Pheochromocytoma cell; p38-MAPK

DOI: https://doi.org/10.1159/000491720

Int J Med Sci. 2018 ;15(8): 832-839

Proscillaridin A induces apoptosis, inhibits STAT3 activation and augments doxorubicin toxicity in prostate cancer cells.

Yangyang He, Muhammad Khan, Jingbo Yang, Min Yao, Shili Yu, Hongwen Gao.

Cardiac glycosides are natural compounds used for the treatment of congestive heart failure and cardiac arrhythmias. Recently, they have been reported to exhibit anticancer activity. Proscillaridin A (PSN-A), a cardiac glycoside constituent of Urginea maritima has been shown to exhibit anticancer activity. However, the cellular targets and anticancer mechanism of PSN-A in various cancers including prostate cancer remain largely unexplored. In the present study, we have shown that PSN-A inhibits proliferation and induces apoptosis in prostate cancer cells in a dose-dependent manner. Further mechanistic study have shown that anticancer activity of PSN-A in prostate cancer cells is associated with ROS generation, Bcl-2 family proteins modulation, mitochondrial membrane potential disruption and ultimately activation of caspase-3 and cleavage of PARP. Moreover, we found that PSN-A inhibits JAK2/STAT3 signaling and augments doxorubicin toxicity in prostate cancer cells. Of note, LNCaP cells were found to be more sensitive to PSN-A treatment as compared to DU145 cells. Taken together, the data provided first evidence of the anticancer activity and possible molecular mechanism of PSN-A in prostate cancer. Further study is needed to develop PSN-A into a potential lead compound for the treatment of prostate cancer.

Keywords: Bcl-2; Cardiac glycosides; Proscillaridin A; Prostate cancer; STAT3

DOI: https://doi.org/10.7150/ijms.23270