Calebin-A induces apoptosis and modulates MAPK family activity in drug resistant human gastric cancer cells

Li, Yan; Li, Shaoqing; Han, Yueheng; Liu, Junye; Zhang, Jian; Li, Fuyang; Wang, Yun; Liu, Xinping; Yao, Libo

doi:10.1016/j.ejphar.2008.06.065

Cited by 56 publications

(48 citation statements)

References 31 publications

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“…Inhibition of the MDK-ERK-RSK pathway decreases cell surface P-gp expression by promoting degradation. In addition, the modulation of ERK activation has been suggested to reverse multidrug resistance in prostate, gastric and hematopoietic cancer (20,21). Similarly, in the present study, the phosphorylation of ERK2 was higher in MCF-7/Taxol, MX-1/ Taxol cells, as well as in the Taxol-resistant xenograft MX-1, and was down-regulated by Aurora A silencing.…”

Section: A B C Dsupporting

confidence: 64%

Function of Aurora kinase A in Taxol-resistant breast cancer and its correlation with P-gp

Tang

Zhang

et al. 2011

Mol Med Report

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Section: A B C Dsupporting

confidence: 64%

Function of Aurora kinase A in Taxol-resistant breast cancer and its correlation with P-gp

Tang

Zhang

et al. 2011

Mol Med Report

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“…For example, suppression of the MEK-ERK signaling pathway by PD98059 increased rather than decreased cisplatin resistance (28). In addition, inhibition of p38 MAPK significantly reduced gemcitabine sensitivity in NTUB1 cells, and Calebin-A enhanced the cytotoxicity of vincristine in SGC7901/vincristine cells through the inhibition of JNK (29,30). The exact effect of the modulation of MAPKs depends on the cell types and crosstalk among the various pathways.…”

Section: Discussionmentioning

confidence: 99%

Triptolide exerts pro-apoptotic and cell cycle arrest activity on drug-resistant human lung cancer A549/Taxol cells via modulation of MAPK and PI3K/Akt signaling pathways

et al. 2016

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Abstract. Multidrug resistance (MDR) is a major obstacle in the effective chemotherapeutic treatment of cancers. Triptolide (TPL) is a diterpenoid isolated from Tripterygium wilfordii Hook. f., a traditional Chinese medicine. It was demonstrated in our previous study that TPL exerts anti-MDR cancers on various MDR cell lines (including A549/Taxol, MCF-7/ADR and Bel7402/5-Fu). The present study was designed to investigate its anti-proliferative activity on A549/Taxol cells, and explore the underlying mechanism of action. The anti-proliferative activity of TPL on A549/Taxol cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Its pro-apoptosis and cell cycle arrest activities were analyzed by flow cytometry. Western blot assay was employed to investigate the levels of mitogen-activated protein kinases (MAPKs) and apoptosis-related proteins in cells. TPL efficiently suppressed the proliferation of A549/Taxol cells. Co-treatment with MAPK inhibitors in the MTT assay indicated that the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways were involved in the process. Upregulation of p-p38, p-ERK, p-GSK-3β, Bax and cleaved caspases-3 and -9, and downregulation of p-JNK, p-Akt and Bcl-2 were observed upon treatment with TPL in the A549/Taxol cells. The results from flow cytometry assay revealed that TPL induced apoptosis and S-phase arrest in A549/Taxol cells. This occurred as a result of the upregulation of p-ERK and p-GSK-3β, and the downregulation of p-JNK and p-Akt, and was responsible for the subsequent anti-proliferative activity.

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“…The role of ERK pathway in the generation of MDR has received more consideration than before, and some specific blocking agents of the ERK pathway have been found. Recent studies demonstrated that modulation of ERK activation may be a new method to reverse MDR [15,22] . However, whether ERK activation is positively or negatively correlated with MDR still remains controversial.…”

Section: Discussionmentioning

confidence: 99%

“…It has been recently found that P-gp expression in the MDR1-transduced human breast cancer cell lines MCF-7/MDR and MDA-MB-231/MDR is positively regulated by the ERK pathway and blockade of the MEK-ERK-RSK pathway can suppress cell surface P-gp expression by promoting its degradation [12] . In addition, there are several lines of evidence that modulation of ERK activation may reverse MDR in prostatic, gastric and hematopoietic cancers [13][14][15][16] . However, there is little evidence that ERK activity is related to MDR of HCC.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells

Feng¹,

Wang²,

Pan³

et al. 2009

WJG

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AIM:To study the expression and phosphorylation of extracellular signal-regulated kinase (ERK) 1 and ERK2 in multidrug resistant (MDR) hepatocellular carcinoma (HCC) cells. METHODS:MDR HCC cell lines, HepG2/adriamycin (ADM) and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein (P-gp) and multidrug resistant protein 1 (MRP1) expression levels. ERK1 and ERK2 mRNA expression levels were measured by quantitative real-time PCR (QRT-PCR). Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot. RESULTS:MTT assay showed that HepG2/ADM and SMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells (8.92% ± 0.22% vs 0.88% ± 0.05%, P < 0.001) and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells (7.37% ± 0.26% vs 1.74% ± 0.25%, P < 0.001). However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION: ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells.

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Calebin-A induces apoptosis and modulates MAPK family activity in drug resistant human gastric cancer cells

Cited by 56 publications

References 31 publications

Function of Aurora kinase A in Taxol-resistant breast cancer and its correlation with P-gp

Function of Aurora kinase A in Taxol-resistant breast cancer and its correlation with P-gp

Triptolide exerts pro-apoptotic and cell cycle arrest activity on drug-resistant human lung cancer A549/Taxol cells via modulation of MAPK and PI3K/Akt signaling pathways

Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells

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