Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways

Hsia, Te Chun; Yu, Chih Chieh; Hsiao, Yung Ting; Wu, Shin Hwar; Bau, Da Tian; Lu, Hsu Feng; Huang, Yi Ping; Lin, Jaung Geng; Chang, Sun‐Yran; Chung, Jing Gung

doi:10.21873/anticanres.11187

Cited by 35 publications

(24 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, cantharidin dose-dependently decreased the phosphorylation levels of ERK, JNK, and p38 MAPK, as well as MEK, suggesting that cantharidin regulated the MAPK signaling pathway. Consistent with the results of this study, another study has shown that cantharidin inhibits cell migration and invasion of human lung cancer NCI-H460 cells via UPA and MAPK signaling pathways (29). However, a previous report has found that only p38 and JNK/MAPK are involved in cantharidin-mediated cell apoptosis in leukemia U937 cells (28).…”

Section: Discussionsupporting

confidence: 90%

Cantharidin suppressed breast cancer MDA-MB-231 cell growth and migration by inhibiting MAPK signaling pathway

Zhao

et al. 2017

Braz J Med Biol Res

View full text Add to dashboard Cite

As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays a crucial role in cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment. In a xenograft model of breast cancer, cantharidin inhibited tumor growth in a dose-dependent manner. Moreover, high doses of cantharidin treatment inhibited cell migration in wound and healing assay and downregulated protein levels of major matrix metalloproteinases (MMP)-2 and MMP-9. MDA-MB-231 cell migration and invasion were dose-dependently inhibited by cantharidin treatment. Interestingly, the members of the mitogen-activated protein kinase (MAPK) signaling family were less phosphorylated as the cantharidin dose increased. Cantharidin was hypothesized to exert its anticancer effect through the MAPK signaling pathway. The data of this study also highlighted the possibility of using PP2A as a therapeutic target for breast cancer treatment.

show abstract

Section: Discussionsupporting

confidence: 90%

Cantharidin suppressed breast cancer MDA-MB-231 cell growth and migration by inhibiting MAPK signaling pathway

Zhao

et al. 2017

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…Previous studies have indicated that MAPK signaling pathways play a critical role in CTD and NCTD‐modulated cell apoptosis and motility in different cancer types . In a further investigation for the underlying molecular mechanisms involved in CAC‐induced apoptosis, the expressions of MAPK member proteins and their phosphorylation status were monitored in HL‐60 cell in this study.…”

Section: Resultsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…After centrifugation, there were divided into two parts, one was the cytosolic fractions (cytosolic extracts) and other part was the nuclear pellets which were re‐suspended in 25 μL of sample buffer named nuclear extracts. Both cytosolic and nuclear extracts were quantitated the total protein and were examined by western blotting with 10% SDS‐polyacrylamide gel (PAGE) for NF‐κB‐p65 protein expression level as previously described …”

Section: Methodsmentioning

confidence: 99%

Tetrandrine inhibits human brain glioblastoma multiforme GBM 8401 cancer cell migration and invasion in vitro

Jiang

Cheng

Kuo

et al. 2018

Environmental Toxicology

View full text Add to dashboard Cite

Tetrandrine (TET) has been reported to induce anti-cancer activity in many human cancer cells and also to inhibit cancer cell migration and invasion. However, there are no reports to show TET inhibits cell migration and invasion in human brain glioblastoma multiforme GBM 8401 cells. In this study, we investigated the anti-metastasis effects of TET on GBM 8401 cells in vitro. Under sub-lethal concentrations (from 1, 5 up to 10 μM), TET significantly inhibited cell mobility, migration and invasion of GBM 8401 cells that were assayed by wound healing and Transwell assays. Gelatin zymography assay showed that TET inhibited MMP-2 activity in GBM 8401 cells. Western blotting results indicated that TET inhibited several key metastasis-related proteins, such as p-EGFR (Tyr1068) , SOS-1, GRB2, Ras, p-AKT (Ser473) and p-AKT (Thr308) , NF-κB-p65, Snail, E-cadherin, N-cadherin, NF-κB, MMP-2 and MMP-9 that were significant reduction at 24 and 48 hours treatment by TET. TET reduced MAPK signaling associated proteins such as p-JNK1/2 and p-c-Jun in GBM 8401 cells. The electrophoretic mobility shift (EMSA) assay was used to investigate NF-κB and DNA binding was reduced by TET in a dose-dependently. Based on these findings, we suggested that TET could be used in anti-metastasis of human brain glioblastoma multiforme GBM 8401 cells in the future. K E Y W O R D S GBM 8401 cells, migration and invasion, MMP-2, NF-κB, Tetrandrine (TET) 1 | INTRODUCTION Malignant glioblastoma multiforme (GBM) are the most common and aggressive malignant primary brain tumor in humans and can be a fatal tumor because of difficulties in treating the related metastasis due to the high proliferation rate and invasiveness. 1-5 Currently, the treatment of GBM is the local irradiation, and conventional chemotherapy with temozolomide (TMZ) or surgical resection in combination with radiotherapy and chemotherapy but the median survival rate is only 8-15 months. 4-6 About 20% of patients after treated with TMZ have shown the clinical toxicity. 7 Due to the side effects of TMZ chemotherapy that leading to the limited efficiency. Thus, bases on the Yun-Lian Lin and Jing-Gung Chung contributed equally to this study.

show abstract

Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways

Cited by 35 publications

References 40 publications

Cantharidin suppressed breast cancer MDA-MB-231 cell growth and migration by inhibiting MAPK signaling pathway

Cantharidin suppressed breast cancer MDA-MB-231 cell growth and migration by inhibiting MAPK signaling pathway

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

Tetrandrine inhibits human brain glioblastoma multiforme GBM 8401 cancer cell migration and invasion in vitro

Contact Info

Product

Resources

About