Showing papers by "Quan Chen published in 2009"
TL;DR: Combination of the 2 agents synergistically arrests the cell cycle, decreases activity of BCR/ABL, and leads to activation of intrinsic and extrinsic apoptosis pathways through complex modifications to both transcription and protein levels suggest potential clinical benefits of IM/AS combination therapy for human CML.
Abstract: In this study, we show that combined use of Imatinib (IM) and arsenic sulfide [As4S4 (AS)] exerts more profound therapeutic effects in a BCR/ABL-positive mouse model of chronic myeloid leukemia (CML) than either drug as a single agent. A systematic analysis of dynamic changes of the proteome, phosphoproteome, and transcriptome in K562 cells after AS and/or IM treatment was performed to address the mechanisms underlying this synergy. Our data indicate that AS promotes the activities of the unfolded protein reaction (UPR) and ubiquitination pathway, which could form the biochemical basis for the pharmacological effects of this compound. In this CML model, AS targets BCR/ABL through the ubiquitination of key lysine residues, leading to its proteasomal degradation, whereas IM inhibits the PI3K/AKT/mTOR pathway. Combination of the 2 agents synergistically arrests the cell cycle, decreases activity of BCR/ABL, and leads to activation of intrinsic and extrinsic apoptosis pathways through complex modifications to both transcription and protein levels. Thus, these results suggest potential clinical benefits of IM/AS combination therapy for human CML.
119 citations
TL;DR: It is shown for the first time that selenite can activate the apoptotic machinery through redox-dependent activation of Bax and further suggest that seenite could be useful in cancer therapy.
63 citations
TL;DR: It is reported that targeted expression of UCP2 to mouse liver increases susceptibility to acute liver injury induced by lipopolysaccharide (LPS) and galactosamine (GalN) and suggests a potential role of U CP2 in the development of liver diseases.
49 citations
TL;DR: It is reported for the first time that Parkin modulates sensitivity of the chemotherapeutic agent paclitaxel in breast cancer, via a microtubule‐dependent mechanism and suggests that patients harbouring tumours with high Parkin level would be more likely to benefit from pac litaxel‐containing regimens.
Abstract: Parkin is an E3 ubiquitin ligase encoded by the Parkin gene (also called PARK2, located at 6q25.2-q27) and is involved in the pathogenesis of Parkinson's disease and the development of cancer. Recently, Parkin has been demonstrated to interact with the microtubule cytoskeleton. However, the biological implication of the Parkin-microtubule axis has been poorly explored. In this study, we report for the first time that Parkin modulates sensitivity of the chemotherapeutic agent paclitaxel in breast cancer, via a microtubule-dependent mechanism. Our data reveal that Parkin binds to the outer surface of microtubules and increases paclitaxel-microtubule interaction, resulting in enhanced paclitaxel-induced microtubule assembly and stabilization. Our data further show that Parkin promotes the activity of paclitaxel to trigger multinucleation and apoptosis, rendering breast cancer cells more sensitive to this drug. Moreover, Parkin expression correlates with the pathological response of tumours to preoperative paclitaxel-containing chemotherapy. In addition, expression of Parkin also correlates with the sensitivity of paclitaxel in primary cultures of breast cancer cells. Our results identify Parkin as a novel mediator of paclitaxel sensitivity in breast cancer. In addition, our study suggests that patients harbouring tumours with high Parkin level would be more likely to benefit from paclitaxel-containing regimens.
49 citations
TL;DR: The results reveal a new mechanism by which caveolin-1 negatively regulates TRAIL-induced apoptosis in human hepatocarcinoma cells.
35 citations
TL;DR: The proprieties of gossypol family are revisited, their using as anticancer agents for cancer therapy and the diverse group of BH3-only proteins facilitate MOMP and thus promote cell death.
Abstract: It is widely thought that Bcl-2 family proteins regulate commitment to apoptosis primarily through their capacity to control the permeability of the mitochondrial outer membrane permeabilization (MOMP) triggers the release of multiple apoptogenic factors into the cytosol and, thereby apoptosis. Various Bcl-2 family members affect this key event of the apoptotic cascade in different ways, determining their pro- or anti-apoptotic status. The Bcl-2-type proteins inhibit MOMP, thereby preserving cell viability. In contrast, Bax-type proteins and the diverse group of BH3-only proteins facilitate MOMP and thus promote cell death. Recently, several drugs that act as BH3 mimetics have been identified, including Gossypol. This review revisits the proprieties of gossypol family, their using as anticancer agents for cancer therapy.
3 citations