Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells

Wang, Peng; Gao, Chang; Wang, Wei; Yao, Liping; Zhang, Jing; Zhang, Sun-Dong; Li, Ji; Fang, Shaohong; Fu, Yujie

doi:10.1016/j.fct.2018.04.004

Cited by 36 publications

(23 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In HFD-fed mice, we found reduced p-JNK and p-BCN1 levels after genetic as well as pharmacological inhibition of ASK1, indicating that ASK1 regulates hepatic lipid accumulation via the JNK-autophagy axis. In support of latter axis, JNK inhibition blunted autophagy in hepatocytes (Zhang et al, 2016a;Wang et al, 2018). In agreement with our findings, hepatic JNK1-knockout mice develop hepatic steatosis (Sabio et al, 2009).…”

Section: Discussionsupporting

confidence: 91%

Liver ASK1 protects from non‐alcoholic fatty liver disease and fibrosis

et al. 2019

View full text Add to dashboard Cite

Non‐alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and may progress to non‐alcoholic steatohepatitis (NASH) and liver fibrosis. The deficit of pharmacological therapies for the latter mainly results from an incomplete understanding of involved pathological mechanisms. Herein, we identify apoptosis signal‐regulating kinase 1 (ASK1) as a suppressor of NASH and fibrosis formation. High‐fat diet‐fed and aged chow‐fed liver‐specific ASK1‐knockout mice develop a higher degree of hepatic steatosis, inflammation, and fibrosis compared to controls. In addition, pharmacological inhibition of ASK1 increased hepatic lipid accumulation in wild‐type mice. In line, liver‐specific ASK1 overexpression protected mice from the development of high‐fat diet‐induced hepatic steatosis and carbon tetrachloride‐induced fibrosis. Mechanistically, ASK1 depletion blunts autophagy, thereby enhancing lipid droplet accumulation and liver fibrosis. In human livers of lean and obese subjects, ASK1 expression correlated negatively with liver fat content and NASH scores, but positively with markers for autophagy. Taken together, ASK1 may be a novel therapeutic target to tackle NAFLD and liver fibrosis.

show abstract

Section: Discussionsupporting

confidence: 91%

Liver ASK1 protects from non‐alcoholic fatty liver disease and fibrosis

et al. 2019

View full text Add to dashboard Cite

show abstract

“…resveratrol has been revealed to inhibit the proliferation of a549 lung cancer cells and to promote cell death by an autophagic mechanism (41). Juglone conferred protection in human hepatocellular carcinoma cells, mediated by its ability to induce apoptosis and autophagy by adjustment of mitogen-activated protein kinase pathways (42). recently, several lines of evidence have also demonstrated that matrine has potential anticancer properties by enhancing autophagy.…”

Section: Discussionmentioning

confidence: 99%

Matrine exerts anti‑breast cancer activity by mediating apoptosis and protective autophagy via the AKT/mTOR pathway in MCF‑7 cells

Jinwen

Song

et al. 2020

Mol Med Rep

View full text Add to dashboard Cite

Matrine, a major alkaloid isolated from the traditional chinese herb Sophora flavescens, has been used clinically to treat breast cancer in china. However, the effects of matrine on apoptosis and autophagy in breast cancer cells remain unclear. in the present study, the anti-breast cancer capacity of matrine was evaluated and its role in regulating apoptosis and autophagy in vitro was investigated. Matrine significantly inhibited the growth of McF-7 cells. in addition, Hoechst 33342 staining and annexin V/propidium iodide staining demonstrated that incubation with matrine induced apoptosis in McF-7 cells. Furthermore, matrine induced autophagy in McF-7 cells, manifesting as an accumulation of light chain 3 ii and downregulation of p62. additionally, matrine suppressed aKT and mammalian target of rapamycin (mTor) phosphorylation, indicating that the aKT/mTor pathway is involved in matrine-induced apoptosis and autophagy. overall, the results of the present study indicated that matrine possesses anti-breast cancer activity by providing protective autophagy via inhibition of the aKT/mTor pathway. These findings indicated that matrine may be a promising candidate for drug development targeting breast cancer.

show abstract

“…In addition, juglone has been reported to influence a variety of other cell signaling pathways. It was found to activate MAP kinases including ERK, JNK and p38 in skin cells [121], glioblastoma cells [122], cervical cancer cells [123], melanoma cells [30], hepatocellular carcinoma cells [124], and smooth muscle cells [125]. In particular, cell signaling modulations of MAP kinases by juglone have been attributed to the mechanism of the induction of apoptosis.…”

Section: Effects Of Juglone On Cell Signaling Pathwaysmentioning

confidence: 99%

“…In particular, cell signaling modulations of MAP kinases by juglone have been attributed to the mechanism of the induction of apoptosis. Some studies have shown that the MAP kinase activation is dependent on the production of ROS [30,122,123,124], suggesting that the redox cycling of naphthoquinones may be responsible for the mechanism.…”

Section: Effects Of Juglone On Cell Signaling Pathwaysmentioning

confidence: 99%

Juglone in Oxidative Stress and Cell Signaling

2019

View full text Add to dashboard Cite

Juglone (5-hydroxyl-1,4-naphthoquinone) is a phenolic compound found in walnuts. Because of the antioxidant capacities of phenolic compounds, juglone may serve to combat oxidative stress, thereby protecting against the development of various diseases and aging processes. However, being a quinone molecule, juglone could also act as a redox cycling agent and produce reactive oxygen species. Such prooxidant properties of juglone may confer health effects, such as by killing cancer cells. Further, recent studies revealed that juglone influences cell signaling. Notably, juglone is an inhibitor of Pin1 (peptidyl-prolyl cis/trans isomerase) that could regulate phosphorylation of Tau, implicating potential effects of juglone in Alzheimer’s disease. Juglone also activates mitogen-activated protein kinases that could promote cell survival, thereby protecting against conditions such as cardiac injury. This review describes recent advances in the understanding of the effects and roles of juglone in oxidative stress and cell signaling.

show abstract

Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells

Cited by 36 publications

References 45 publications

Liver ASK1 protects from non‐alcoholic fatty liver disease and fibrosis

Liver ASK1 protects from non‐alcoholic fatty liver disease and fibrosis

Matrine exerts anti‑breast cancer activity by mediating apoptosis and protective autophagy via the AKT/mTOR pathway in MCF‑7 cells

Juglone in Oxidative Stress and Cell Signaling

Contact Info

Product

Resources

About