Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy

Chu, Binxiang; Chen, Shenao; Zheng, Xiongwei; Ye, Jiajing; Xu, Cheng; Zhang, Liwei; Guo, Deyin; Wang, Peng; Hong, Dun; Hong, Zhenghua

doi:10.1111/jcmm.16055

Cited by 14 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6B ). One previous study revealed that TRAF6 is the major E3 ubiquitinligase that causes the K63-mediated ubiquitination of Beclin-1 [ 27 , 28 ], were confirmed by the results in the present study. And we found that knockdown of TRAF6 expression reduced K63-mediated ubiquitination of Beclin-1 (Fig.…”

Section: Resultssupporting

confidence: 92%

IL-17B/IL-17RB signaling cascade contributes to self-renewal and tumorigenesis of cancer stem cells by regulating Beclin-1 ubiquitination

et al. 2021

View full text Add to dashboard Cite

Cancer stem cells (CSCs) are characterized by robust self-renewal and tumorigenesis and are responsible for metastasis, drug resistance, and angiogenesis. However, the molecular mechanisms for the regulation of CSC homeostasis are incompletely understood. This study demonstrated that the interleukin-17 (IL-17)B/IL-17RB signaling cascade promotes the self-renewal and tumorigenesis of CSCs by inducing Beclin-1 ubiquitination. We found that IL-17RB expression was significantly upregulated in spheroid cells and Lgr5-positive cells from the same tumor tissues of patients with gastric cancer (GC), which was closely correlated with the degree of cancer cell differentiation. Recombinant IL-17B (rIL-17B) promoted the sphere-formation ability of CSCs in vitro and enhanced tumor growth and metastasis in vivo. Interestingly, IL-17B induced autophagosome formation and cleavage-mediated transformation of LC3 in CSCs and 293T cells. Furthermore, inhibition of autophagy activation by ATG7 knockdown reversed rIL-17B-induced self-renewal of GC cells. In addition, we showed that IL-17B also promoted K63-mediated ubiquitination of Beclin-1 by mediating the binding of tumor necrosis factor receptor-associated factor 6 to Beclin-1. Silencing IL-17RB expression abrogated the effects of IL-17B on Beclin-1 ubiquitination and autophagy activation in GC cells. Finally, we showed that IL-17B level in the serum of GC patients was positively correlated with IL-17RB expression in GC tissues, and IL-17B could induce IL-17RB expression in GC cells. Overall, the results elucidate the novel functions of IL-17B for CSCs and suggest that the intervention of the IL-17B/IL-17RB signaling pathway may provide new therapeutic targets for the treatment of cancer.

show abstract

Section: Resultssupporting

confidence: 92%

IL-17B/IL-17RB signaling cascade contributes to self-renewal and tumorigenesis of cancer stem cells by regulating Beclin-1 ubiquitination

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Studies shows anti-carcinogenic potential of various phytochemicals such as carotenoids, chlorophyll, flavonoids, indole, isothiocyanate, polyphenolic compounds, protease inhibitors, sulfides, and terpens [37]. Natural active flavonoid that are abandoned in various plants has been proved to exhibit multiple biological effects possessing anti-apoptotic, anti-inflammatory, anti-oxidant and anti-cancer properties [70]. The specific mechanisms of action of most phytochemicals in cancer prevention are not yet clear but appear to be varied [71].…”

Section: Resultsmentioning

confidence: 99%

Phytochemicals based therapeutic approaches for Breast cancer targeting: Molecular docking study

Parihar

Puranik

Khandia

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Cancer is a prominent cause of disease burden all over the world. Primary cause of the development of cancer is exposure to potentially hazardous environmental factors and unhealthy lifestyle. Among all types of cancer, breast cancer is most common in women and becomes a public health issue on a global scale. There has been considerable interest in the development of drugs which can target cancer-causing hotspot factors such as mTOR, estrogen receptor alpha, and progesterone receptor to cure breast cancer. The key focus of the present work is to search plant-based phytochemical molecules which can efficiently interact with the targeted proteins responsible for the development and progression of breast cancer using molecular docking studies. Methods: We have screened 1064 phytochemical molecules from plant sources against 5 potential hotspot targets: EGFR kinase domain, Human estrogen receptor alpha ligand-binding domain, FRB fragment of mTOR, Progesterone receptor, and NUDT5 of breast cancer. Results: Our results show that among all molecules, 25 phytochemicals exhibit promising therapeutic potential for breast cancer treatment. Our observation is further strengthened by the available literatures showing the promising therapeutic efficacy exhibited by these lead molecules in in vitro and in vivo cancer models. Conclusion: The virtual screening of phytochemicals hold promise to search potential anticancer drug. Among the lead molecules, Delphinidin 3,5-diglucoside, Baicalein, and Morphine have already been known for their anticancer properties, but the efficacy of Vitexin, IsoSkimmiwallin, Nodifloretin, Jaceosidin and Nepetin have not been explored so far and therefore further in-vitro and in-vivo study is warranted

show abstract

“…Various osteoclast markers reduced in the SR group, including RANK, TRAF6, NFATc2, c-Fos, and some proteases related to bone resorption, such as MMP-9, MMP-14, and CTSK. These proteases could degrade extracellular matrix protein, including collagen and elastin, break intercellular connections, and promote cell development and migration [ 15 , 35 , 38 , 39 , 40 ] In addition, orthodontic tooth movement at the pressure side of the first molars was inhibited in the SR group, according to the analysis of 3D reconstruction with micro-CT. The inhibition of tooth movement might result from the fact that SR significantly enhances the micro-architecture of trabecular bone by attenuating osteoclast differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, the NF-κB pathway has been proven to play an important role in autophagy, and the strong link between autophagy and osteoclastogenesis is being increasingly appreciated [ 15 ]. Autophagy, a highly conserved catabolic process in eukaryotes, is responsible for phagocytosing and degrading damaged organelles or aged proteins via the lysosomal pathway.…”

Section: Introductionmentioning

confidence: 99%

Strontium Ranelate Inhibits Osteoclastogenesis through NF-κB-Pathway-Dependent Autophagy

Sun

Zhao

et al. 2023

Bioengineering

View full text Add to dashboard Cite

Strontium ranelate (SR) is a pharmaceutical agent used for the prevention and treatment of osteoporosis and fragility fracture. However, little attention has been paid to the effect of SR on alveolar bone remodeling during orthodontic tooth movement and its underlying mechanism. Here, we investigated the influence of SR on orthodontic tooth movement and tooth resorption in Sprague–Dawley rats and the relationship between the nuclear factor–kappa B (NF-κB) pathway, autophagy, and osteoclastogenesis after the administration of SR in vitro and in vivo. In this study, it was found that SR reduced the expression of autophagy-related proteins at the pressure side of the first molars during orthodontic tooth movement. Similarly, the expression of these autophagy-related proteins and the size and number of autophagosomes were downregulated by SR in vitro. The results also showed that SR reduced the number of osteoclasts and suppressed orthodontic tooth movement and root resorption in rats, which could be partially restored using rapamycin, an autophagy inducer. Autophagy was attenuated after pre-osteoclasts were treated with Bay 11-7082, an NF-κB pathway inhibitor, while SR reduced the expression of the proteins central to the NF-κB pathway. Collectively, this study revealed that SR might suppress osteoclastogenesis through NF-κB-pathway-dependent autophagy, resulting in the inhibition of orthodontic tooth movement and root resorption in rats, which might offer a new insight into the treatment of malocclusion and bone metabolic diseases.

show abstract

Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy

Cited by 14 publications

References 41 publications

IL-17B/IL-17RB signaling cascade contributes to self-renewal and tumorigenesis of cancer stem cells by regulating Beclin-1 ubiquitination

IL-17B/IL-17RB signaling cascade contributes to self-renewal and tumorigenesis of cancer stem cells by regulating Beclin-1 ubiquitination

Phytochemicals based therapeutic approaches for Breast cancer targeting: Molecular docking study

Strontium Ranelate Inhibits Osteoclastogenesis through NF-κB-Pathway-Dependent Autophagy

Contact Info

Product

Resources

About