Cantharidic acid induces apoptosis through the p38 MAPK signaling pathway in human hepatocellular carcinoma

Feng, I‐Che; Hsieh, Ming‐Ju; Chen, Pei‐Ni; Hsieh, Yi‐Hsien; Ho, Hsin‐Yu; Yang, Shun‐Fa; Yeh, Chao‐Bin

doi:10.1002/tox.22513

Cited by 19 publications

(18 citation statements)

References 46 publications

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“…Additionally, our results match a previous study which reported that, Bax deletion, an apoptotic protein, in a hepatocyte‐specific BCL‐xL knockout model, suppressed hepatocarcinogenesis . However, our results are in contrast with previous studies showing that activation of the ASK1‐p38 MAPK signalling cascade induces apoptosis in many HCC cell lines . Additionally, Bao et al reported that p38 MAPK induces apoptosis in HepG2 and Huh7 cells through upregulation of apoptosis‐related proteins, including p53, caspases and Bcl‐2 proteins …”

Section: Discussionsupporting

confidence: 84%

A novel chemoprotective effect of tiopronin against diethylnitrosamine‐induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK‐P53 signalling cascade

Mo’men

Hussein

Kandeil

2019

Clin Exp Pharma Physio

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related death worldwide. Oxidative stress contributes significantly to HCC pathogenesis. In this study, we investigated the possible chemoprotective effect of the thiol group‐containing compound, tiopronin, against HCC induced chemically by diethylnitrosamine (DENA) in rats. In addition, we elucidated the possible underlying molecular mechanism. Adult male Wistar rats were divided into: Control group, DENA‐treated group and tiopronin + DENA‐treated group. Liver function tests (ALT, AST, ALP, albumin, total and direct bilirubin) as well as alpha fetoprotein (AFP) concentration were measured in the sera of samples. Oxidative stress biomarkers such as malondialdehyde, nitric oxide, catalase and glutathione peroxidase were measured in the liver tissue homogenates. Determination of the phosphorylated apoptosis signal‐regulating kinase 1 (phospho‐ASK1), phospho‐P38 and phospho‐P53 proteins by western blotting, caspase 3 by immunofluorescence in addition to histopathological examination of the liver tissues were performed. Our results showed that tiopronin prevented the DENA‐induced elevation of the liver function enzymes and AFP. It also preserved the activities of antioxidant enzymes as well as providing protection from the appearance of HCC histopathological features. Interestingly, tiopronin significantly decreased the expression level of phospho‐ASK1, phospho‐P38 and phospho‐P53, caspase 3 in the liver tissues. These novel findings suggested that tiopronin is an antioxidant drug with a chemoprotective effect against DENA‐induced HCC through maintaining the normal activity of ASK1/ P38 MAPK/ P53 signalling pathway.

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Section: Discussionsupporting

confidence: 84%

A novel chemoprotective effect of tiopronin against diethylnitrosamine‐induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK‐P53 signalling cascade

Mo’men

Hussein

Kandeil

2019

Clin Exp Pharma Physio

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“…CAC was reported to inhibit growth of oral squamous cell carcinoma (OSCC) and testicular germ cell tumor respectively through endoplasmic reticulum (ER) stress and unfolded protein response (UPR) induction and ERK‐mediated caspase‐3 activation . Moreover, Feng et al reports that CAC induces apoptosis in SK‐Hep‐1 cells through a p38‐mediated apoptotic pathway …”

Section: Introductionmentioning

confidence: 99%

Cantharidic acid induces apoptosis of human leukemic HL‐60 cells via c‐Jun N‐terminal kinase‐regulated caspase‐8/‐9/‐3 activation pathway

Wang

Chow

Chien

et al. 2018

Environmental Toxicology

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Cantharidin, a natural toxin from blister beetles, has shown potent anticancer activities on many solid tumor cells. Recently, cantharidin and its analogue, norcantharidin, were also shown to suppress nonsolid tumors such as chronic myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However, there is no available information to address the effects of cantharidic acid (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study showed that CAC, at a range of concentrations (0-20 μM), concentration-dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot and flow cytometric assays demonstrated that CAC induced several features of apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced concentration- and time- dependent activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK-specific inhibitor can reverse the CAC-induced activation of the caspase-8, -9, and -3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC can be regulated by JNK activation signaling.

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“…Seol et al's [ 30 ] results suggest that Riluzole, an amyotrophic lateral sclerosis (ALS) drug, has an anticancer effect on HCC. Feng et al [ 31 ] reported that cantharidic acid inhibits HCC cell proliferation by inducing cell apoptosis through the p38 MAPK signaling pathway. Nwosu et al [ 32 ] reported that downregulated genes (HCC versus non-HCC) were enriched in the PPAR signaling pathway based on each of the 8 HCC datasets downloaded from the Gene Expression Omnibus (GEO).…”

Section: Discussionmentioning

confidence: 99%

Detecting Differentially Variable MicroRNAs via Model-Based Clustering

Wang

et al. 2018

International Journal of Genomics

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Identifying differentially variable (DV) genomic probes is becoming a new approach to detect novel genomic risk factors for complex human diseases. The F test is the standard equal-variance test in statistics. For high-throughput genomic data, the probe-wise F test has been successfully used to detect biologically relevant DNA methylation marks that have different variances between two groups of subjects (e.g., cases versus controls). In addition to DNA methylation, microRNA (miRNA) is another important mechanism of epigenetics. However, to the best of our knowledge, no studies have identified DV miRNAs. In this article, we proposed a novel model-based clustering method to improve the power of the probe-wise F test to detect DV miRNAs. We imposed special structures on covariance matrices for each cluster of miRNAs based on the prior information about the relationship between variances in cases and controls and about the independence among them. Simulation studies showed that the proposed method seems promising in detecting DV probes. Based on two real datasets about human hepatocellular carcinoma (HCC), we identified 7 DV-only miRNAs (hsa-miR-1826, hsa-miR-191, hsa-miR-194-star, hsa-miR-222, hsa-miR-502-3p, hsa-miR-93, and hsa-miR-99b) using the proposed method, one (hsa-miR-1826) of which has not yet been reported to be related to HCC in the literature.

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Cantharidic acid induces apoptosis through the p38 MAPK signaling pathway in human hepatocellular carcinoma

Cited by 19 publications

References 46 publications

A novel chemoprotective effect of tiopronin against diethylnitrosamine‐induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK‐P53 signalling cascade

A novel chemoprotective effect of tiopronin against diethylnitrosamine‐induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK‐P53 signalling cascade

Cantharidic acid induces apoptosis of human leukemic HL‐60 cells via c‐Jun N‐terminal kinase‐regulated caspase‐8/‐9/‐3 activation pathway

Detecting Differentially Variable MicroRNAs via Model-Based Clustering

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