Jnk signaling pathway-mediated regulation of Stat3 activation is linked to the development of doxorubicin resistance in cancer cell lines

Kim, Ju-Hwa; Lee, Seok Chul; Ro, Jungsil; Han, Kang; Kim, Hyung Sik; Yoon, Sungpil

doi:10.1016/j.bcp.2009.09.008

Cited by 61 publications

(41 citation statements)

References 34 publications

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“…The expression and activation of STAT3 is significantly increased in paclitaxel-resistant ovarian cancer cells and tissues, and the inhibition of STAT3 reduces paclitaxel resistance (17,25). Similar findings are reported in DOX-resistant human cancer cells including breast and liver cancer and neuroblastoma (26,27). However, the role of STAT3 in the acquisition of TMZ-resistance in glioma has yet to be determined.…”

Section: Discussionsupporting

confidence: 59%

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Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells

Lee¹,

Ko²,

Joe³

et al. 2010

Oncology Letters

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Abstract. The alkylating agent temozolomide (TMZ) is an effective drug used for the treatment of malignant gliomas. However, tumor relapse combined with the development of drug resistance remains a significant problem. To clarify the mechanism of the resistance of glioma cells to TMZ chemotherapy, TMZ-resistant glioma cell lines (TR cells) were generated using U373 and U251 human glioma cells, and TMZ-resistance was confirmed via viability and apoptosis assays. The TMZ-resistance of TR cells was not associated with the TMZ-resistance molecule O 6 -methylguanine-DNAmethyltransferase. Notably, the expression level of signal transducers and activators of transcription 3 (STAT3) and serine 727-phosphorylated STAT3 (pSTAT3-Ser727) was highly increased in TR cells, while that of 705-phosphorylated STAT3 (pSTAT3-Tyr705) was decreased. The inhibition of STAT3 expression by small interfering RNA enhanced TR cell TMZ sensitivity. These results suggest that STAT3 contributes to TMZ-resistance in gliomas and is a potential target for the reversal of TMZ-resistance in patients with a recurrent glioma.

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Section: Discussionsupporting

confidence: 59%

“…This activation transfers the expression of genes such as Bcl-2, survivin and cyclin D1. STAT3 may be correlated to drug resistance through tyrosine phosphorylation (24)(25)(26). In the present study, however, TMZ-resistance was increased in a viability assay while pSTAT-Tyr705 was decreased in TR cells (Fig.…”

Section: Discussioncontrasting

confidence: 44%

Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells

Lee¹,

Ko²,

Joe³

et al. 2010

Oncology Letters

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“…Rp-cAMPs (10-100 µM; Werner et al, 2014;Mangiavacchi and Wolf, 2004;Wang et al, 2012;Pratt et al, 2016;Vallejo and Vallejo, 2002); Ro 31-8220 (1-10 µM; Lee et al, 2013;Montejo-López et al, 2016), PD 98059 (10-50 µM; Sutter et al, 2004;Kim et al, 2008), SP 600125 (20 µM; Hah et al, 2013;Kim et al, 2010) and Akt inhibitor XI (1 µM; Frampton et al,2012;Rybchyn et al, 2011 Inhibitor Cocktail 2). Cell lysates were scraped and clarified by centrifugation at 4°C for 10 min at 14000 x g prior to being assayed for TG activity using the biotin-labeled cadaverine incorporation assay (see below).…”

Section: Cell Extraction For Measurement Of Tg2 Activitymentioning

confidence: 99%

Role of transglutaminase 2 in PAC1 receptor mediated protection against hypoxia-induced cell death and neurite outgrowth in differentiating N2a neuroblastoma cells

Algarni

Hargreaves

Dickenson

2017

Biochemical Pharmacology

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“…Stat3 activation is a predictive marker of drug resistance because it is linked to the development of doxorubicin resistance in cancer cell lines. 11,45,46 We found that cucurbitacin D decreased the levels of p-Akt and p-Stat3 in MCF7, MDA-MB-231, and SKBR3 cells. However, doxorubicin alone did not decrease p-Akt and p-Stat3 levels.…”

Section: Discussionmentioning

confidence: 76%

Cucurbitacin D exhibits its anti-cancer effect in human breast cancer cells by inhibiting Stat3 and Akt signaling

Hong

Kim

et al. 2018

Eur J Inflamm

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Cucurbitacins are triterpenoids commonly found in Cucurbitaceae and Cruciferae and have long been used in traditional medicine. Cucurbitacins demonstrate anti-inflammatory and anti-cancer activities. We investigated whether cucurbitacin D affects viability in breast cancer cells and its mechanism of action. An MTT assay was used to measure the viability of breast cancer cells. Western blot analysis was used to measure the expression of various modulators, such as p-p53, p-Stat3, p-Akt, and p-NF-κB. Doxorubicin and cucurbitacin D affected the viability of MCF7, MDA-MB-231, and SKBR3 cells. Cucurbitacin D and doxorubicin increased p-p53 expression in MCF7, SKBR3, and MDA-MB-231 cells. Cucurbitacin D suppressed p-Akt, p-NF-κB, and p-Stat3 expression in MCF7, MDA-MB-231, and SKBR3 cells. Doxorubicin alone did not decrease p-Akt and p-Stat3 levels. Cucurbitacin D decreased p-NF-κB and p-Stat3 levels. Doxorubicin in combination with cucurbitacin D increased p-p53 levels and suppressed Akt, NF-κB, Stat3, and Bcl-2 expression more than cucurbitacin D alone. Our results clearly demonstrate that cucurbitacin D could be a useful compound for treating human breast cancer.

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Jnk signaling pathway-mediated regulation of Stat3 activation is linked to the development of doxorubicin resistance in cancer cell lines

Cited by 61 publications

References 34 publications

Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells

Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells

Role of transglutaminase 2 in PAC1 receptor mediated protection against hypoxia-induced cell death and neurite outgrowth in differentiating N2a neuroblastoma cells

Cucurbitacin D exhibits its anti-cancer effect in human breast cancer cells by inhibiting Stat3 and Akt signaling

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