SIMSIR , Méliné

Resistance to chemotherapy can be studied comparatively to the study of resistance in microorganisms. Among the protein superfamily identified as being responsible for multidrug resistance are RND. Its members are widespread in bacterial organisms, but also in Archaea and Eukaryotes. Ptch1, a transmembrane protein, receptor of morphogen...

RND family proteins are transmembrane proteins identified as large spectrum drug transporters. A prototypical case in this superfamily, responsible for antibiotic resistance in selected gram negative bacteria, is AcrB. AcrB forms a trimer, which uses the proton motive force to efflux drugs, implementing a functional rotation mechanism....

RND family proteins are transmembrane proteins identified as large spectrum drug trans-porters involved in multi-drug resistance. A prototypical case in this superfamily, responsiblefor antibiotic resistance in selected gram negative bacteria, is AcrB. AcrB forms a trimer usingthe proton motive force to efflux drugs, implementing a functional...

Adrenocortical carcinoma (ACC) presents a high risk of relapse and metastases with outcomes not improving despite extensive research and new targeted therapies. We recently showed that the Hedgehog receptor Patched is expressed in ACC, where it strongly contributes to doxorubicin efflux and treatment resistance. Here, we report the...

International audience

International audience

We previously reported that methiothepin, a small molecule known as a nonselective serotonin 5-HT receptor antagonist, inhibited the doxorubicin efflux activity of the Hedgehog receptor Ptch1 and enhanced the cytotoxic, pro-apoptotic, anti-proliferative, and anti-clonogenic effects of doxorubicin on adrenocortical carcinoma cells. Here, we show...

The development of inhibitors of key biological mechanisms involved in multidrug resistance (MDR) burden meets an important medical need but still represents a challenging task. Major MDR targets in both bacterial and cancer cells are multidrug efflux systems. Several aspects should be considered in the attempt to design efficient inhibitors of...

We previously reported that methiothepin, a small molecule known as a nonselective serotonin 5-HT receptor antagonist, inhibited the doxorubicin efflux activity of the Hedgehog receptor Ptch1 and enhanced the cytotoxic, pro-apoptotic, anti-proliferative, and anti-clonogenic effects of doxorubicin on adrenocortical carcinoma cells. Here, we show...

We previously reported that methiothepin, a small molecule known as a nonselective serotonin 5-HT receptor antagonist, inhibited the doxorubicin efflux activity of the Hedgehog receptor Ptch1 and enhanced the cytotoxic, pro-apoptotic, anti-proliferative, and anti-clonogenic effects of doxorubicin on adrenocortical carcinoma cells. Here, we show...

Melanoma patients harboring the BRAF V600E mutation are treated with vemurafenib. Almost all of them ultimately acquire resistance, leading to disease progression. Here, we find that a small molecule from a marine sponge, panicein A hydroquinone (PAH), overcomes resistance of BRAF V600E melanoma cells to vemurafenib, leading to tumor...