β-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma

Zhang, Guangya; He, Jiangping; Ye, Xiaofei; Zhu, Jing; Hu, Xi; Shen, Minyan; Ma, Yuru; Mao, Ziming; Song, Huai‐Dong; Chen, Fengling

doi:10.1038/s41419-019-1492-6

Cited by 122 publications

(85 citation statements)

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“…The MAPK signaling pathway is downstream of ROS and plays an essential role in the induction of apoptosis and autophagy 48 . Many studies have demonstrated that ROS accumulation could induce cell death through MAPK activation 49,50 . Western blot results indicated that apparent increases in the phosphorylation levels of ERK and JNK and NAC almost abolished this effect mediated by BD.…”

Section: Discussionmentioning

confidence: 99%

Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo

et al. 2020

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Worldwide, lung cancer remains a leading cause of cancer mortality. Bruceine D (BD) has been shown to induce pancreatic cancer cell death via several different mechanisms. In this study, we demonstrated that BD inhibited lung cancer cell proliferation. Apoptosis and autophagy were the most important mechanisms involved in BD-induced lung cancer cell death, and complete autophagic flux was observed in A549 and NCI-H292 cells. In addition, BD significantly improved intracellular reactive oxygen species (ROS) levels. BD-mediated cell apoptosis and autophagy were almost inhibited in cells pretreated with N-acetylcysteine (NAC), an ROS scavenger. Furthermore, MAPK signaling pathway activation contributed to BD-induced cell proliferation inhibition and NAC could eliminate p-ERK and p-JNK upregulation. Finally, an in vivo study indicated that BD inhibited the growth of lung cancer xenografts. Overall, BD is a promising candidate for the treatment of lung cancer owing to its multiple mechanisms and low toxicity.

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Section: Discussionmentioning

confidence: 99%

Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo

et al. 2020

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“…37,38 MAPK is an important transmitter of signals from the cell surface to the nucleus that can be activated by various extracellular stimuli such as cytokines, neurotransmitters, hormones, cell stress and cell adhesion. 39,40 NF-κB p65 and JAK2/STAT1 signalling pathways are involved in inflammation through complex molecular regulation. In a previous study, our team demonstrated that 15-Deoxy-△-12,14-Prostaglandin J2 (15d-PGJ2) can improve liver function by activating PPAR-γ to inhibit NF-κB p65, and the role and mechanism of the PPAR-γ natural ligand activator-15d-PGJ2 in liver has since reviewed.…”

Section: Discussionmentioning

confidence: 99%

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

Xiang

Chen

et al. 2020

DDDT

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These authors contributed equally to this workObjective: Hepatic ischemia reperfusion (IR) limits the development of liver transplantation technology. The aim of this study was to explore the protective effects of Bergenin on hepatic IR, particularly the elimination of reactive oxygen species (ROS) and activation of the peroxisome proliferators activated receptor γ (PPAR-γ) pathway. Methods: Initial experiments were performed to confirm the non-toxicity of Bergenin. Mice were randomly divided into sham, IR, and IR + Bergenin (10, 20 and 40 mg/kg) groups, and serum and tissue samples were obtained at 2, 8 and 24 h for detection of liver enzymes (ALT and AST), inflammatory factors (TNF-α, IL-6 and IL-1β), ROS, cell death markers (Bcl-2, Bax, Beclin-1 and LC3) and related important pathways (PPAR-γ, P38 MAPK, NF-κB p65 and JAK2/STAT1). Results: Bergenin reduced the release of ROS, down-regulated inflammatory factors, and inhibited apoptosis and autophagy. Additionally, expression of PPAR-γ-related genes was increased and phosphorylation of P38 MAPK, NF-κB p65 and JAK2/STAT1-related proteins was decreased in Bergenin pre-treatment groups in a dose-dependent manner. Conclusion: Bergenin exerts hepatic protection by eliminating ROS, affecting the release of inflammatory factors, and influencing apoptosis-and autophagy-related genes via the PPAR-γ pathway in this model of hepatic IR injury.

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“…We next added PI in the amount of 5 μl in order to stain the cells followed by incubation for 5 min in the dark. Using BD FACS Calibur (BD Biosciences, Mountain View, CA, USA) we measured the levels and degree of cell apoptosis (Zhang et al, 2019a). For TUNEL analysis, briefly, cells were incubated with TUNEL labeling (marked with Green fluorescence) mix for 60 min at 37°C, and then we used DAPI (marked with Blue fluorescence, Sigma, USA) for double dyeing.…”

Section: Cell Cycle and Apoptosis Analysismentioning

confidence: 99%

Sotetsuflavone Induces Autophagy in Non-Small Cell Lung Cancer Through Blocking PI3K/Akt/mTOR Signaling Pathway in Vivo and in Vitro

Wang

et al. 2019

Front. Pharmacol.

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Non-small cell lung cancer (NSCLC) is a globally scaled disease with a high incidence and high associated mortality rate. Autophagy is one of the important physiological activities that helps to control cell survival, influences the dynamics of cell death, and which plays a crucial role in the pathophysiology of NSCLC. Sotetsuflavone is a naturally derived and occurring flavonoid, and previous studies have demonstrated that sotetsuflavone possesses potential anti-cancer activities. However, whether or not sotetsuflavone induces autophagy, as well as has effects and influences cell death in NSCLC cells remains unclear. Thus, in our study, we examined and elucidated the roles and underlying mechanisms of sotetsuflavone upon the dynamics of autophagy in NSCLC in vivo and in vitro. The results indicated that sotetsuflavone was able to inhibit proliferation, migration, and invasion of NSCLC cells. Mechanistically, sotetsuflavone was able to induce apoptosis by increasing the levels of expression of cytochrome C, cleaved-caspase 3, cleaved-caspase 9, and Bax, and contrastingly decreased levels of expression of Bcl-2. In addition, we also found that decreased levels of expression of cyclin D1 and CDK4 caused arrest of the G0/G1 phases of the cell cycle. Furthermore, we also found that sotetsuflavone could induce autophagy which in turn can play a cytoprotective effect on apoptosis in NSCLC. Sotetsuflavone-induced autophagy appeared related to the blocking of the PI3K/Akt/ mTOR pathway. Our in vivo study demonstrated that sotetsuflavone significantly inhibited the growth of xenograft model inoculated A549 tumor with high a degree of safety. Taken together, these findings suggest that sotetsuflavone induces autophagy in NSCLC cells through its effects upon blocking of the PI3K/Akt/mTOR signaling pathways. Our study may provide a theoretical basis for future clinical applications of sotetsuflavone and its use as a chemotherapeutic agent for treatment of NSCLC.

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β-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma

Cited by 122 publications

References 44 publications

Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo

Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

Sotetsuflavone Induces Autophagy in Non-Small Cell Lung Cancer Through Blocking PI3K/Akt/mTOR Signaling Pathway in Vivo and in Vitro

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