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Atractylenolide‐III (AT‐III) is well known as its role in antioxidant and anti‐inflammatory. Present study was aimed to figure out its effects on osteoarthritis and potential mechanisms. Rat model, human osteoarthritis cartilage explants as well as rat/human chondrocyte cultures were prepared to test AT‐III's effects on osteoarthritis progression and chondrocyte senescence. Potential targeted molecules of AT‐III were predicted using network pharmacology and molecular docking, assessed by Western blotting and then verified with rescue experiments. AT‐III treatment alleviated osteoarthritis severity (shown by OARSI grading score and micro‐CT) and chondrocyte senescence (indexed by levels of SA‐β‐gal, P16, P53, MMP13, ROS and ratio of healthy/collapsed mitochondrial membrane potentials). Network pharmacology and molecular docking suggested that AT‐III might play role through NF‐κB pathway. Further experiments revealed that AT‐III reduced phosphorylation of IKKα/β, IκBα and P65 in NF‐κB pathway. As well as nuclear translocation of p65. Both in vivo and in vitro experiments indicated that AT‐III's effects on osteoarthritis and anti‐senescence were reversed by an NF‐κB agonist. AT‐III could alleviate osteoarthritis by inhibiting chondrocyte senescence through NF‐κB pathway, which indicated that AT‐III is a prospective drug for osteoarthritis treatment. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the roles and underlying mechanisms of YAP in the proliferation of neuroblastoma cells. Methods: The expression level of YAP was evaluated by Western blotting and immunocytochemistry. Cell viability, cell proliferation and growth were detected by CCK‐8, PH3 and Ki67 immunostaining, and the real‐time cell analyser system. The nuclear and cytoplasmic proteins of p27Kip1 were dissociated by the nuclear‐cytosol extraction kit and were detected by Western blotting and immunocytochemistry. mRNA levels of Akt, CDK5 and CRM1 were determined by qRT‐PCR. Results: YAP was enriched in SH‐SY5Y cells (a human neuroblastoma cell line). Knock‐down of YAP in SH‐SY5Y cells or SK‐N‐SH cell line (another human neuroblastoma cell line) significantly decreased cell viability, inhibited cell proliferation and growth. Mechanistically, knock‐down of YAP increased the nuclear location of p27Kip1, whereas serum‐induced YAP activation decreased the nuclear location of p27Kip1 and was required for cell proliferation. Meanwhile, overexpression of YAP in these serum‐starved SH‐SY5Y cells decreased the nuclear location of p27Kip1, promoted cell proliferation and overexpression of p27Kip1 in YAP‐activated cells inhibited cell proliferation. Furthermore, knock‐down of YAP reduced Akt mRNA and protein levels. Overexpression of Akt in YAP‐downregulated cells decreased the nuclear location of p27Kip1 and accelerated the proliferation of SH‐SY5Y cells. Conclusions: Our studies suggest that YAP promotes the proliferation of neuroblastoma cells through negatively controlling the nuclear location of p27Kip1 mediated by Akt. [ABSTRACT FROM AUTHOR]

Glioma is currently the most widespread and malignant primary intracranial tumor, which is characterized by high heterogeneity and high fatality rates. β-elemene, which is a bioactive compound extracted from a Chinese herb, Curcuma wenyujin, has been reported to reduce resistance of chemotherapeutic drugs and induce apoptosis in tumor cells. However, the role and mechanisms of β-elemene in glioma senescence remains unknown. In the present study, we found that a low concentration of β-elemene (10 μg/mL) induced senescence in glioma cells, including reduction of cell proliferation, hypertrophic morphology, increase of senescence-associated β-galactosidase (SA-β-Gal) activity, upregulation of several senescence-associated genes such as p16, p53 and NF-κB , and downregulation of Lamin B1 . However, a high concentration of β-elemene induced apoptosis in glioma cells. Treatment with β-elemene caused a marked down-regulation of Yes-associated protein (YAP) expression in glioma cells, which is a key transcriptional co-activator in multiple cancers. Moreover, cyclin dependent kinase 6 (CDK6), which is a known downstream target of YAP, was decreased in glioma cells that treated with β-elemene. The overexpression of YAP and CDK6 significantly rescued β-elemene-induced senescence in glioma cells. Finally, β-elemene treatment also induced the senescence of glioma cells in glioma xenograft model through inactivation of YAP-CDK6 pathways, which might inhibit the glioma growth. Taken together, these results reveal a previously unknown role of β-elemene in glioma cell senescence in vitro and in vivo that is associated with YAP-CDK6 signaling pathway, which will enhance our understanding of glioma cell senescence, and provide novel strategies for the treatment of gliomas., Competing Interests: None., (AJCR Copyright © 2021.)

Objective: We aimed to investigate the roles and underlying mechanisms of YAP in the proliferation of neuroblastoma cells., Methods: The expression level of YAP was evaluated by Western blotting and immunocytochemistry. Cell viability, cell proliferation and growth were detected by CCK-8, PH3 and Ki67 immunostaining, and the real-time cell analyser system. The nuclear and cytoplasmic proteins of p27 Kip1 were dissociated by the nuclear-cytosol extraction kit and were detected by Western blotting and immunocytochemistry. mRNA levels of Akt, CDK5 and CRM1 were determined by qRT-PCR., Results: YAP was enriched in SH-SY5Y cells (a human neuroblastoma cell line). Knock-down of YAP in SH-SY5Y cells or SK-N-SH cell line (another human neuroblastoma cell line) significantly decreased cell viability, inhibited cell proliferation and growth. Mechanistically, knock-down of YAP increased the nuclear location of p27 Kip1 , whereas serum-induced YAP activation decreased the nuclear location of p27 Kip1 and was required for cell proliferation. Meanwhile, overexpression of YAP in these serum-starved SH-SY5Y cells decreased the nuclear location of p27 Kip1 , promoted cell proliferation and overexpression of p27 Kip1 in YAP-activated cells inhibited cell proliferation. Furthermore, knock-down of YAP reduced Akt mRNA and protein levels. Overexpression of Akt in YAP-downregulated cells decreased the nuclear location of p27 Kip1 and accelerated the proliferation of SH-SY5Y cells., Conclusions: Our studies suggest that YAP promotes the proliferation of neuroblastoma cells through negatively controlling the nuclear location of p27 Kip1 mediated by Akt., (© 2019 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.)