Journal ArticleDOI
Hyaluronan oligosaccharides sensitize lymphoma resistant cell lines to vincristine by modulating P‐glycoprotein activity and PI3K/Akt pathway
Rosalia I. Cordo Russo,Mariana Garcia,Laura Alaniz,Guillermo A. Blanco,Elida Alvarez,Silvia E. Hajos +5 more
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TLDR
It is reported for the first time that oHA per se modulate MDR in lymphoma cells by decreasing p‐Akt as well as Pgp activity, thus suggesting that o HA could be useful in combination with classical chemotherapy in MDR hematological malignancies.Abstract:
Multidrug resistance (MDR) is one of the main reasons for failure of cancer therapy. It may be mediated by overexpression of ATP-dependent efflux pumps or by alterations in survival or apoptotic pathways. Fragments generated by enzymatic degradation of hyaluronan (oHA) were able to modulate growth and cell survival and sensitize MDR breast cancer cells to cytotoxic drugs. In this work the relationship between oHA and MDR in lymphoid malignancies was analyzed using murine lymphoma cell lines resistant to doxorubicin (LBR-D160) or vincristine (LBR-V160) and a sensitive line (LBR-). After oHA treatment, higher apoptosis levels were observed in the resistant cell lines than in the sensitive one. Besides, oHA sensitized LBR-D160 and LBR-V160 to vincristine showing increased apoptosis induction when used in combination with vincristine. Native hyaluronan failed to increase apoptosis levels. As different survival factors could be modulated by hyaluronan, we investigated the PI3K/Akt pathway through PIP3 production and phosphorylated Akt (p-Akt) and survivin expression was also evaluated. Our results showed that oHA decreased p-Akt in the 3 cell lines while anti-CD44 treatment abolished this effect. Besides, survivin was downregulated only in LBR-V160 by oHA. When Pgp function was evaluated, we observed that oHA were able to inhibit Pgp efflux in murine and human resistant cell lines in a CD44-dependent way. In summary, we report for the first time that oHA per se modulate MDR in lymphoma cells by decreasing p-Akt as well as Pgp activity, thus suggesting that oHA could be useful in combination with classical chemotherapy in MDR hematological malignancies.read more
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Hyaluronic acid for anticancer drug and nucleic acid delivery.
TL;DR: The rationale underlying approaches, chemical strategies, and recent advances in the use of HA to design drug carriers for delivering anticancer agents, are reviewed and descriptions are given of HA-based drug conjugates, particulate carriers, inorganic nanostructures, and hydrogels.
Journal ArticleDOI
Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells.
Lilly Y.W. Bourguignon,Karine Peyrollier,Karine Peyrollier,Weiliang Xia,Weiliang Xia,Eli Gilad,Eli Gilad +6 more
TL;DR: It is suggested that targeting HA/CD44-mediated Nanog-Stat-3 signaling pathways and ankyrin/cytoskeleton function may represent a novel approach to overcome chemotherapy resistance in some breast and ovarian tumor cells displaying stem cell marker properties during tumor progression.
Journal ArticleDOI
Hyaluronan-CD44 Interaction with Protein Kinase Cϵ Promotes Oncogenic Signaling by the Stem Cell Marker Nanog and the Production of MicroRNA-21, Leading to Down-regulation of the Tumor Suppressor Protein PDCD4, Anti-apoptosis, and Chemotherapy Resistance in Breast Tumor Cells
TL;DR: This study investigated the hyaluronan (HA)-induced interaction between CD44 (a primary HA receptor) and protein kinase Cϵ (PKCϵ), which regulates a number of human breast tumor cell functions, to provide important drug targets for sensitizing tumor cell apoptosis and overcoming chemotherapy resistance in breast cancer cells.
Journal ArticleDOI
Modulation of P-glycoprotein efflux pump: induction and activation as a therapeutic strategy
Renata Silva,Vânia Vilas-Boas,Helena Carmo,Ricardo Jorge Dinis-Oliveira,Ricardo Jorge Dinis-Oliveira,Félix Carvalho,Maria de Lourdes Bastos,Fernando Remião +7 more
TL;DR: In this review, a new focus is brought on the therapeutic interest of inducing and/or activating P-gp for limiting the toxicity caused by its substrates, and several in vivo and in vitro studies validating the use of such a therapeutic strategy are discussed.
Journal ArticleDOI
Hyaluronan: molecular size-dependent signaling and biological functions in inflammation and cancer.
Anastasia G. Tavianatou,Ilaria Caon,Marco Franchi,Zoi Piperigkou,Zoi Piperigkou,Devis Galesso,Nikos K. Karamanos,Nikos K. Karamanos +7 more
TL;DR: The primary goal of this review is to critically present the importance of HA molecular size on cellular signaling, functional cell properties, and morphology in normal and pathological conditions, including inflammation and cancer.
References
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Journal ArticleDOI
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