A novel indirubin derivative PHII-7 potentiates adriamycin cytotoxicity via inhibiting P-glycoprotein expression in human breast cancer MCF-7/ADR cells

Shi, Ruizan; Li, Wei; Zhang, Xiuli; Zhang, Yanjun; Peng, Hongwei; Xie, Yinliang; Fan, Daiming; Liu, Rong; Liu, Xuyi; Xiong, Dongsheng

doi:10.1016/j.ejphar.2011.07.047

Cited by 20 publications

(14 citation statements)

References 41 publications

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“…A similar study in HT-29 cells and DU145 human prostate carcinoma cells showed UA-mediated apoptosis is enhanced by inhibition of upstream inducers of p38 such as Src (23). Also, while one report showed a number of chemoresistant cancer cell types were sensitive to UA, UA-mediated cytotoxicity was still stronger in the parental cell types (24), which have lower levels of P-gp (25, 26). In addition, another study showed that UA inhibits substrate efflux through P-gp at high concentrations.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol and P-glycoprotein Inhibitors Enhance the Anti-Skin Cancer Effects of Ursolic Acid

Junco

Mancha

Malik

et al. 2013

Molecular Cancer Research

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Ursolic acid (UA), present in apples, rosemary, and other sources, is known to inhibit tumor formation and tumor cell viability in multiple systems, including skin. However, various cancers are resistant to UA treatment. Herein, skin carcinoma cells (Ca3/7) as compared to skin papilloma cells (MT1/2) displayed more resistance to UA-induced cytotoxicity. Interestingly, Ca3/7 cells had elevated levels of P-glycoprotein (P-gp), an ATP-dependent efflux pump that mediates resistance to chemotherapy in pre-clinical and clinical settings, and not only accumulated less but also more rapidly expelled the P-gp substrate Rhodamine 123 (Rh123) indicating UA is transported by P-gp. To determine if P-gp inhibition can enhance UA-mediated cytotoxicity, cells were challenged with P-gp inhibitors verapamil (VRP) or cyclosporin A (CsA). Alternatively, cells were pre-treated with the natural compound resveratrol (RES), a known chemotherapy sensitizer. VRP and RES enhanced the effects of UA in both cell lines, while CsA only did so in Ca3/7 cells. Similarly, VRP inhibited Rh123 efflux in both lines, while CsA only inhibited Rh123 efflux in Ca3/7 cells. RES did not inhibit Rh123 efflux in either line, indicating the synergistic effects of RES and UA are not manifest by inhibition of P-gp-mediated efflux of UA. These results indicate that the anti-skin cancer effects of UA are enhanced with P-gp inhibitors. In addition, RES and UA interact synergistically, but not through inhibition of P-gp. Implications Resveratrol and/or p-glycoprotein inhibitors in combination with ursolic acid are an effective anti-skin cancer regimen.

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Section: Introductionmentioning

confidence: 99%

Resveratrol and P-glycoprotein Inhibitors Enhance the Anti-Skin Cancer Effects of Ursolic Acid

Junco

Mancha

Malik

et al. 2013

Molecular Cancer Research

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“…To select for MCF-7/ADR cells that were nearly 40 times more resistant to doxorubicin than MCF-7 cells, doxorubicin (1μg/ml) was added to cultures of MCF-7/ADR cells until 2 weeks before the cells were exposed to experimental conditions. Cell density was adjusted every 3 days by separating the cells with 0.25% trypsin with 0.02% ethylenediaminetetraacetic acid (EDTA) in phosphate-buffered saline, then diluting them with fresh growth medium [14].…”

Section: Methodsmentioning

confidence: 99%

“…The derivative PHII-7 (which resembles indirubin [ Figure 1], the active agent of the traditional Chinese herbal medicine, Danggui Longhui Wan, used to treat human chronic myelogenous leukemia [12,13]) can overcome multidrug resistance effectively. By decreasing the level of P-glycoprotein in multidrug resistant cancers, PHII-7 allows an intracellular concentration of anti-cancer drugs sufficient to induce apoptosis [14]. Our primary objective was to determine whether treating human metastatic cancer cells with slightly toxic doses of PHII-7 would decrease their migration and invasion.…”

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confidence: 99%

Inhibitory effects of indirubin derivative PHII-7 on invasion and migration in metastatic cancer

Xue¹,

Yang²,

Wu³

et al. 2015

neo

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“…Several mechanisms of drug resistance have been examined. Overexpression of a membrane efflux transporter, P-glycoprotein (P-gp) (Shi et al, 2011) (Romero et al, 2011), changes in topoisomerase II activity (Romero et al, 2011), modifications in glutathione S-transferase (Romero et al, 2012), and altered expression of apoptosis-associated protein Bcl-2 (Bjerre et al, 2012;Larsen et al, 2012) and tumor suppressor protein p53 . ERα status, although lesser known, have also been studied in connection with MDR.…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor α Roles in Breast Cancer Chemoresistance

Jiang²,

Zhou³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor α, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. ERα is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive ERα expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of ERα with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

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A novel indirubin derivative PHII-7 potentiates adriamycin cytotoxicity via inhibiting P-glycoprotein expression in human breast cancer MCF-7/ADR cells

Cited by 20 publications

References 41 publications

Resveratrol and P-glycoprotein Inhibitors Enhance the Anti-Skin Cancer Effects of Ursolic Acid

Resveratrol and P-glycoprotein Inhibitors Enhance the Anti-Skin Cancer Effects of Ursolic Acid

Inhibitory effects of indirubin derivative PHII-7 on invasion and migration in metastatic cancer

Estrogen Receptor α Roles in Breast Cancer Chemoresistance

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