Hyaluronan oligosaccharides sensitize lymphoma resistant cell lines to vincristine by modulating P‐glycoprotein activity and PI3K/Akt pathway

Russo, R; Garcı́a, Mariana; Alaniz, Laura; Blanco, Guillermo; Álvarez, Élida; Hajos, Silvia E.

doi:10.1002/ijc.23122

Cited by 71 publications

(47 citation statements)

References 35 publications

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“…When hyaluronan oligosaccharides inhibit the interaction between hyaluronan and cancer cells, PI3K/Akt survival signaling in vitro is suppressed, and tumor growth in vivo is reduced (Ghatak et al 2002). Hyaluronan oligosaccharides also modulate MDR in lymphoma cells by decreasing the phosphorylation of Akt and P-glycoprotein activity (Cordo-Russo et al 2008). Furthermore, hyaluronan oligosaccharide treatment decreases BCRP expression and inhibits Akt activation in malignant glioma cells (Gilg et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling

Liu

Chang

et al. 2009

Cell Tissue Res

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Little information is available concerning multidrug resistance (MDR) in mesenchymal stem cells, although several studies have reported that MDR is associated with hyaluronan in neoplastic cells. We have evaluated whether a hyaluronan-coated surface modulates MDR in placenta-derived human mesenchymal stem cells (PDMSCs). We have found that PDMSCs cultured on a tissue-culture polystyrene surface coated with 30 microg/cm(2) hyaluronan are more resistant than control PDMSCs to doxorubicin. Inhibiting PI3K/Akt signaling has shown that the PI3K/Akt pathway modulates both P-glycoprotein activity and doxorubicin resistance. In addition, 10 microM verapamil dramatically suppresses the doxorubicin resistance induced by the hyaluronan-coated surface, indicating that P-glycoprotein activity is necessary for MDR. We have further found that PDMSCs treated with CD44 small interfering RNA (siRNA) and grown on a polystyrene surface coated with 30 microg/cm(2) hyaluronan have fewer P-glycoprotein(+) cells and lower CD44 expression levels (less than 60% in both cases) than PDMSCs not treated with CD44 siRNA and grown on the hyaluronan-coated surface. Moreover, treatment with CD44 siRNA suppresses the hyaluronan-substratum-induced doxorubicin resistance. We conclude that a hyaluronan substratum induces MDR in PDMSCs through CD44 signaling.

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Section: Discussionmentioning

confidence: 99%

Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling

Liu

Chang

et al. 2009

Cell Tissue Res

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“…In addition, it was reported that long-term treatment of genistein could induce the related protein expression of first-pass metabolism in mice [14,15] and the activities of phase II metabolic enzymes in mice could be mediated by oligosaccharides [13,16,17]. Moreover, some non-digestible carbohydrates, such as hyaluronan oligosaccharides and astragalus polysaccharides, were shown to inhibit P-gp, MRP1, and MRP2 expression, thereby contributing to an increase in intracellular concentration of food ingredients or drugs [18,19]. Accordingly, we suppose that stachyose promoting absorption of genistein may be closely related to inhibition of first-pass metabolism of genistein in the small intestine.…”

Section: Introductionmentioning

confidence: 99%

Non-digestible stachyose promotes bioavailability of genistein through inhibiting intestinal degradation and first-pass metabolism of genistein in mice

Lin

et al. 2017

Food & Nutrition Research

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This study was designed to explore the molecular mechanism of stachyose in enhancing the gastrointestinal stability and absorption of soybean genistein in mice. Male Kunming mice in each group (n = 8) were administered by intragastric gavage with saline, stachyose (250 mg/kg·bw), genistein (100 mg/kg·bw), and stachyose (50, 250, and 500 mg/kg·bw) together with genistein (100 mg/kg·bw) for 4 consecutive weeks, respectively, and then their urine, feces, blood, gut, and liver were collected. UPLC-qTOF/MS analysis showed that levels of genistein and its metabolites (dihydrogenistein, genistein 7-sulfate sodium salt, genistein 4’-β-D-glucuronide, and genistein 7-β-D-glucuronide) in serum and urine were increased with an increase in stachyose dosages in mice. Furthermore, the feces level of genistein aglycone was also elevated by co-treatment of stachyose with genistein. However, the feces concentration of dihydrogenistein, a characteristic metabolite of genistein by gut microorganism, was decreased by stachyose administration in a dose-dependent manner. Additionally, the simultaneous administration with stachyose and genistein in mice could decrease intestinal SULT, UGT, P-gp, and MRP1 expression, relative to the treatment with individual stachyose or genistein. These results demonstrate that stachyose-mediated inhibition against the intestinal degradation of genistein and expression of phase II enzymes and efflux transporters can largely contribute to the elevated bioavailability of soybean genistein.

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“…It has been established that many cancer chemopreventive agents are known to lower cancer risk by suppressing HA/CD44-signaling pathway (Bourguignon et al , 2009; Cordo Russo et al , 2008), which subsequently leads to attenuation of pro-inflammatory mediators and their activities. Natural anti-oxidants like ITSCs found in cruciferous vegetables have been under investigation due to their potential anti-cancer effects.…”

Section: Resultsmentioning

confidence: 99%

Isothiocyanate analogs targeting CD44 receptor as an effective strategy against colon cancer

et al. 2014

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Inflammatory pathway plays an important role in tumor cell progression of colorectal cancers. Although colon cancer is considered as one of the leading causes of death worldwide, very few drugs are available for its effective treatment. Many studies have examined the effects of specific COX-2 and 5-LOX inhibitors on human colorectal cancer, but the role of isothiocyanates (ITSCs) as COX–LOX dual inhibitors engaged in hyaluronan–CD44 interaction has not been studied. In the present work, we report series of ITSC analogs incorporating bioisosteric thiosemicarbazone moiety. These inhibitors are effective against panel of human colon cancer cell lines including COX-2 positive HCA-7, HT-29 cells lines, and hyaluronan synthase-2 (Has2) enzyme over-expressing transformed intestinal epithelial Apc10.1Has2 cells. Specifically, our findings indicate that HA-CD44v6-mediated COX-2/5-LOX signaling mediate survivin production, which in turn, supports anti-apoptosis and chemo-resistance leading to colon cancer cell survival. The over-expression of CD44v6shRNA as well as ITSC treatment significantly decreases the survival of colon cancer cells. The present results thus offer an opportunity to evolve potent inhibitors of HA synthesis and CD44v6 pathway and thus underscoring the importance of the ITSC analogs as chemopreventive agents for targeting HA/CD44v6 pathway.

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Hyaluronan oligosaccharides sensitize lymphoma resistant cell lines to vincristine by modulating P‐glycoprotein activity and PI3K/Akt pathway

Cited by 71 publications

References 35 publications

Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling

Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling

Non-digestible stachyose promotes bioavailability of genistein through inhibiting intestinal degradation and first-pass metabolism of genistein in mice

Isothiocyanate analogs targeting CD44 receptor as an effective strategy against colon cancer

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