16-hydroxy-cleroda-3,13-dien-16,15-olide induced glioma cell autophagy via ROS generation and activation of p38 MAPK and ERK-1/2

Thiyagarajan, Varadharajan; Sivalingam, Kalai Selvi; Viswanadha, Vijaya Padma; Weng, Ching‐Feng

doi:10.1016/j.etap.2016.06.005

Cited by 30 publications

(32 citation statements)

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“…Substantial evidence has demonstrated that p38 and ERK play important roles in regulating autophagy in the areas of acute or chronic tissue injury20, 21 To explore the mechanisms of cell autophagy responsible for the TAK1 signal pathway during cisplatin‐induced AKI, we examined whether TAK1 inhibition affects the phosphorylation of p38 and ERK. Our result showed that cisplatin‐induced AKI increased phosphorylation of p38 and ERK, as detected by Western blotting in kidneys of control group mice.…”

Section: Resultsmentioning

confidence: 99%

“…24 A significant body of evidence suggests that the TGF-b signalling pathway mediates acute renal injury 25,26 and that p38 and ERK, as members of the MAPK family, play a crucial role in autophagy. 20 Therefore, we hypothesized that TAK1 might regulate the p38 and ERK signalling pathways to mediate autophagy involved in the mech- 27 Increasing evidence has manifested that TAK1 is widely expressed in multiple important organs and is involved in the pathophysiological processes of acute injury by regulating and mediating multiple signalling pathways 7,28 In our previous study, we demonstrated that TAK1 mediated apoptosis in ischaemia-reperfusion of the kidney. 29 Ma FY found that TAK1 regulates inflammation and fibrosis in the obstructed kidney.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of TAK1 decreases phosphorylation of p38 and ERK in kidneys of mice with cisplatininduced AKI p38 and ERK are two main subfamilies of mammalian MAPKs, which are a group of serine/threonine-specific protein kinases generally expressed in all cell types and are essential components of signal transduction in various physiological and pathological processes 19. Substantial evidence has demonstrated that p38 and ERK play important roles in regulating autophagy in the areas of acute or chronic tissue injury20,21 To explore the mechanisms of cell autophagy responsible for the TAK1 signal pathway during cisplatin-induced AKI, we examined whether TAK1 inhibition affects the phosphorylation of p38 and ERK. Our result showed that cisplatin-induced AKI increased phosphorylation of p38 and ERK, as detected by Western blotting in kidneys of control group mice.…”

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confidence: 99%

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TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Zhou

Fan

Zhong

et al. 2018

J Cellular Molecular Medi

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The ability of cisplatin (cis‐diamminedichloroplatinum II) toxicity to induce acute kidney injury (AKI) has attracted people's attention and concern for a long time, but its molecular mechanisms are still widely unknown. We found that the expression of transforming growth factor‐β (TGF‐β)‐activated kinase 1 (TAK1) could be increased in kidneys of mice administrated with cisplatin. Autophagy is an evolutionarily conserved catabolic pathway and is involved in various acute and chronic injuries. Moreover, p38 MAPK (mitogen‐activated protein kinase) and ERK regulate autophagy in response to various stimuli. Therefore, our hypothesis is that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells and thus exacerbating kidney damage. Here, BALB/c mice were intraperitoneally injected with a TAK1 inhibitor and were then administrated with sham or cisplatin at 20 mg/kg by intraperitoneal injection. Compared with mice in the vehicle cisplatin group, mice intraperitoneally injected with a TAK1 inhibitor were found to have lower serum creatinine and less tubular damage following cisplatin‐induced AKI. Furthermore, inhibition of TAK1 reduced p38 and Erk phosphorylation, decreased expression of LC3II and reversed the down‐regulation of P62 expression induced by cisplatin. The hypothesis was verified with tubular epithelial cells administrated with cisplatin in vitro. Finally, p38 inhibitor or ERK inhibitor abated autophagy activation and cell viability reduction in tubular epithelial cells treated with cisplatin plus TAK1 overexpression vector. Taken together, our results show that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells that exacerbates kidney damage.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Zhou

Fan

Zhong

et al. 2018

J Cellular Molecular Medi

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“…Tumor cells presented higher level of ROS than normal cells [21]. In addition, high ROS concentration could induce cell apoptosis and necrosis in relation with the severity and the duration of exposure [22]. Therefore, many ROS-inducing agents are currently used in clinical trials for different tumors [21, 23].…”

Section: Discussionmentioning

confidence: 99%

Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma

Zhang

et al. 2017

BMC Neurol

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BackgroundJuglone is a natural pigment, which has cytotoxic effect against various human tumor cells. However, its cytotoxicity to glioma cells, especially to tumor stem-like cells (TSCs) has not been demonstrated.MethodsTSCs of glioma were enriched from U87 and two primary cells (SHG62, and SHG66) using serum-free medium supplemented with growth factors, including bFGF, EGF and B27. After treatment of juglone with gradient concentrations (0, 10, 20, and 40 μM), the viability and apoptosis of TSCs were evaluated by WST-8 assay and flow cytometry. Reactive oxygen species (ROS) was labeled by the cell-permeable fluorescent probe and detected with flow cytometry. ROS scavenger (NAC) and p38-MAPK inhibitor (SB203580) were applied to resist the cytotoxic effect. Caspase 9 cleavage and p38 phosphorylation (P-p38) were quantified by western blot. Juglone as well as temozolomide (TMZ) were administrated in intracranial xenografts and MR scan was performed every week to evaluate the anti-tumor effect in vivo.ResultsJuglone could obviously inhibit the proliferation of TSCs in glioma by decreasing cell viability (P < 0.01) and inducing apoptosis (P < 0.01), which was accompanied by increased caspase 9 cleavage in a dose-dependent manner (P < 0.01). In the meantime, juglone could generate ROS significantly and increase p38 phosphorylation (P < 0.01). In addition, pretreatment with ROS scavenger or p38-MAPK inhibitor could reverse juglone-induced cytotoxicity (P < 0.01). More importantly, juglone could also suppress tumor growth in vivo and improve the survival of U87-bearing mice compared with control (P < 0.05), although TMZ seemed to have better effect.ConclusionsJuglone could inhibit the growth of TSCs in gliomas through the activation of ROS-p38-MAPK pathway in vitro, and the anti-glioma effect was validated in vivo, which offers a potential therapeutic agent to gliomas.

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“…Therefore, by observing the altered levels of cleavage caspase-8, caspase-9, and Bcl-2, the type of chemical-induced apoptosis could be putatively addressed. Previous studies of HCD-induced cancer cell death were focused on autophagic cell death and intrinsic apoptosis [15,16,33,34]. To the best of our knowledge, this study is the first to show the involvement of HCD-induced extrinsic apoptosis in colorectal cancer.…”

Section: Discussionmentioning

confidence: 66%

Clerodane Diterpene Ameliorates Inflammatory Bowel Disease and Potentiates Cell Apoptosis of Colorectal Cancer

et al. 2019

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Inflammatory bowel disease (IBD) is general term for ulcerative colitis and Crohn's disease, which is chronic intestinal and colorectal inflammation caused by microbial infiltration or immunocyte attack. IBD is not curable, and is highly susceptible to develop into colorectal cancer. Finding agents to alleviate these symptoms, as well as any progression of IBD, is a critical effort. This study evaluates the anti-inflammation and anti-tumor activity of 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) in in vivo and in vitro assays. The result of an IBD mouse model induced using intraperitoneal chemical azoxymethane (AOM)/dextran sodium sulfate (DSS) injection showed that intraperitoneal HCD adminstration could ameliorate the inflammatory symptoms of IBD mice. In the in vitro assay, cytotoxic characteristics and retained signaling pathways of HCD treatment were analyzed by MTT assay, cell cycle analysis, and Western blotting. From cell viability determination, the IC 50 of HCD in Caco-2 was significantly lower in 2.30 µM at 48 h when compared to 5-fluorouracil (5-FU) (66.79 µM). By cell cycle and Western blotting analysis, the cell death characteristics of HCD treatment in Caco-2 exhibited the involvement of extrinsic and intrinsic pathways in cell death, for which intrinsic apoptosis was predominantly activated via the reduction in growth factor signaling. These potential treatments against colon cancer demonstrate that HCD could provide a promising adjuvant as an alternative medicine in combating colorectal cancer and IBD.

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16-hydroxy-cleroda-3,13-dien-16,15-olide induced glioma cell autophagy via ROS generation and activation of p38 MAPK and ERK-1/2

Cited by 30 publications

References 59 publications

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma

Clerodane Diterpene Ameliorates Inflammatory Bowel Disease and Potentiates Cell Apoptosis of Colorectal Cancer

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