Induction of autophagy by an oleanolic acid derivative, SZC017, promotes ROS‐dependent apoptosis through Akt and JAK2/STAT3 signaling pathway in human lung cancer cells

Song, Yanlin; Kong, Lingyin; Sun, Bin; Gao, Lei; Chu, Peng; Ahsan, Anil; Qaed, Eskandar; Lin, Yuan; Peng, Jinyong; Ma, Xiaodong; Zhang, Jianbin; Wang, Shisheng; Tang, Zeyao

doi:10.1002/cbin.10868

Cited by 23 publications

(16 citation statements)

References 46 publications

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“…Our RNA-Seq analysis identified multiple genes related to sanshool treatment and UVB irradiation in which the most remarkable results referred to CSF2 and the AKT-JAK2-STAT3 pathway. The JAK2-STAT3 signaling pathway, a core component of organ protection, is involved in various organs 25 . In the current study, sanshool exerted positive effects on the expression and secretion of CSF2 in UVB-irradiated HDFs.…”

Section: Discussionmentioning

confidence: 99%

Sanshool improves UVB-induced skin photodamage by targeting JAK2/STAT3-dependent autophagy

et al. 2019

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Ultraviolet radiation is markedly increased because of pollution and the depletion of the stratospheric ozone layer. Excessive exposure to sunlight can negatively affect the skin, resulting in sunburn, photo-aging, or skin cancer. In this study, we first determined the photoprotective effect of sanshool, a major component in Zanthoxylum bungeanum, on UVB-irradiated responses in human dermal fibroblasts (HDFs) and nude mouse. We found that sanshool treatment can protect cells against the effects of UVB irradiation by (i) increasing cell viability, (ii) inhibiting MMP expression, and (iii) inducing autophagy. We also used the recombinant CSF2 or anti-CSF2 antibody co-cultured with human dermal fibroblasts (HDFs) and found that CSF2 contributes to sanshool-induced autophagy. Sanshool hindered the UVB-induced activation of JAK2-STAT3 signaling in HDFs, thereby inhibiting the expression of MMPs and activation of autophagic flux. Exposure of the dorsal skin of hairless mice to UVB radiation and subsequent topical application of sanshool delayed the progression of skin inflammation, leading to autophagy and inhibiting the activation of JAK2-STAT3 signaling. These results provide a basis for the study of the photoprotective effect of sanshool and suggest that it can be potentially used as an agent against UVB-induced skin damage in humans.

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Section: Discussionmentioning

confidence: 99%

Sanshool improves UVB-induced skin photodamage by targeting JAK2/STAT3-dependent autophagy

et al. 2019

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“…STAT3, a member of the STAT family, may be activated by phosphorylation at the tyrosine residue 705 to regulate the release of growth factors and cytokines in gastric cancer (41). The activation of the JAK2/STAT3 signaling pathway was associated with the growth, migration and metastasis of lung cancer cells (42). Lei et al (43) revealed that the activation of the JAK2/STAT3 signaling pathway may promote the proliferation and migration of cancer cells as well as inhibit apoptosis in renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

EZH2 inhibition suppresses bladder cancer cell growth and metastasis via the JAK2/STAT3 signaling pathway

Chen

Liu

et al. 2019

Oncol Lett

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The aim of the current study was to investigate the role of enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in the progression of bladder cancer. Human bladder cancer tissue samples were analyzed by immunohistochemistry, and the association between the clinicopathological parameters and EZH2 expression was analyzed. The proliferation, apoptosis and migration ability of the human bladder cancer cell lines E-J and 5637 with or without the EZH2 inhibitor UNC1999 was investigated. The effect of UNC1999 was further explored in a xenograft model of nude mice. The in vivo and in vitro expression levels of EZH2, janus kinase 2, signal transducer and activator of transcription 3 and their phosphorylated forms were examined by western blotting. The expression levels of EZH2, JAK2 and STAT3 were increased in bladder cancer tissue compared with normal adjacent tissue. Furthermore, the expression of EZH2 was increased in tumors with a higher TNM Classification of Malignant Tumors stage and histological grade compared with tumors with a lower stage and grade. The human bladder cancer cell lines E-J and 5637 treated with UNC1999 demonstrated reduced cell proliferation, apoptosis and migration compared with cells treated without UNC1999. Additionally, EZH2 may promote the proliferation and migration of bladder cancer via the JAK2/STAT3 pathway. EZH2 may serve an important role in the proliferation and migration of human bladder cancer cells, and may aid in the development of novel treatment strategies for bladder cancer.

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“…Upon phosphorylated by JAK2 at Try705, STAT3 undergoes dimerization and then translocates to the nucleus, where it binds with the promoter regions of target genes to promote their expression (Kurdi and Booz, ). It has been documented that STAT3 extensively participates in the regulation of numerous genes controlling cell survival, metabolism, inflammation, oxidative stress, and angiogenesis (Song et al, ; Wang et al, ). Moreover, STAT3 plays an important role in the hypertrophic growth of cardiomyocytes (Willey et al, ).…”

Section: Discussionmentioning

confidence: 99%

Chrysophanol attenuated isoproterenol‐induced cardiac hypertrophy by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway

Yuan

Hong

Zhang

et al. 2019

Cell Biology International

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Cardiac hypertrophy is a common pathological change found in various cardiovascular diseases. Although it has long been recognized as an important risk factor responsible for heart failure, there is still a lack of effective treatments in clinic. Chrysophanol is a natural compound with multiple biological activities and protective roles in the cardiovascular system. However, its potential effect on cardiac hypertrophy remains unclear. In the current study, we found that chrysophanol could protect against isoproterenol (ISO)‐induced cardiac hypertrophy both in vitro and in vivo. Increase of cell surface and hypertrophic marker expression induced by ISO in neonatal rat cardiomyocytes was downregulated by chrysophanol. Moreover, chrysophanol ameliorated the abnormal changes of cardiac structure and function in rats subjected to ISO injection, as shown by echocardiography and morphometry measurements. Further mechanistical investigation demonstrated that chrysophanol inhibited phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) induced by ISO. Nuclear translocation of STAT3 and transcription of downstream genes promoted by ISO treatment were also remarkably suppressed by chrysophanol. Taken together, our findings revealed that chrysophanol attenuated ISO‐induced cardiac hypertrophy by inhibiting JAK2/STAT3 signaling pathway. Chrysophanol may be a potential candidate compound for the prevention and treatment of hypertrophy‐related cardiomyopathy.

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Induction of autophagy by an oleanolic acid derivative, SZC017, promotes ROS‐dependent apoptosis through Akt and JAK2/STAT3 signaling pathway in human lung cancer cells

Cited by 23 publications

References 46 publications

Sanshool improves UVB-induced skin photodamage by targeting JAK2/STAT3-dependent autophagy

Sanshool improves UVB-induced skin photodamage by targeting JAK2/STAT3-dependent autophagy

EZH2 inhibition suppresses bladder cancer cell growth and metastasis via the JAK2/STAT3 signaling pathway

Chrysophanol attenuated isoproterenol‐induced cardiac hypertrophy by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway

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