VCPA, a novel synthetic derivative of α-tocopheryl succinate, sensitizes human gastric cancer to doxorubicin-induced apoptosis via ROS-dependent mitochondrial dysfunction

Wu, Han; Liu, Shaoping; Gong, Jun; Liu, Jiuyang; Zhang, Qian; Leng, Xiaohong; Zhang, Nian; Li, Yan

doi:10.1016/j.canlet.2017.02.007

Cited by 29 publications

(19 citation statements)

References 46 publications

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“… 10 , 11 , 12 , 13 However, the development of resistance to apoptosis induced by chemotherapeutic drugs during treatment drastically decreases the efficacy of chemotherapy and is a key mechanism of the therapeutic escape of cancer cells and a major obstacle to cancer therapy. 14 , 15 , 16 In addition, all clinical chemotherapeutic agents have severe adverse effects, such as cardiomyopathy, typhlitis, acute myelotoxicity, and other non-specific toxicities induced by high drug doses. 10 , 11 , 12 , 13 Thus, it is urgent to explore potential mechanisms involved in chemotherapy resistance, develop new drugs targeting drug-resistant tumors, and explore new compounds for combination therapy to enhance the therapeutic effects of anti-tumor drugs with minimal adverse effects.…”

Section: Introductionmentioning

confidence: 99%

The Long Noncoding RNA D63785 Regulates Chemotherapy Sensitivity in Human Gastric Cancer by Targeting miR-422a

Zhou

Lin

et al. 2018

Molecular Therapy - Nucleic Acids

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Gastric cancer is one of the most prevalent tumor types in the world. Chemotherapy is the most common choice for cancer treatment. However, chemotherapy resistance and adverse side effects limit its clinical applications. Aberrant expression of long noncoding RNAs (lncRNAs) has been found in various stages of gastric cancer development and progression. In this study, we identified that an oncogenic lncRNA, long intergenic non-protein-coding RNA D63785 (lncR-D63785), is highly expressed in gastric cancer tissues and cells. Silencing of lncR-D63785 inhibited cell proliferation, cell migration and invasion in gastric cancer cell lines and reduced tumor volume and size in mice. We found that the expression of lncR-D63785 was inversely correlated with microRNA 422a (miR-422a) expression, which was involved in the downregulation of expression of myocyte enhancer factor-2D (MEF2D) and drug sensitivity. Knockdown of lncR-D63785 increased the expression of miR-422a and the sensitivity of gastric cancer cells to apoptosis induced by the anticancer drug doxorubicin (DOX). This indicates that lncR-D63785 acts as a competitive endogenous RNA (ceRNA) of miR-422a and promotes chemoresistance by blocking miR-422-dependent suppression of MEF2D. Together, our results suggest that the therapeutic suppression of lncR-D63785 alone or in combination with chemotherapeutic agents may be a promising strategy for treating gastric cancer.

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Section: Introductionmentioning

confidence: 99%

The Long Noncoding RNA D63785 Regulates Chemotherapy Sensitivity in Human Gastric Cancer by Targeting miR-422a

Zhou

Lin

et al. 2018

Molecular Therapy - Nucleic Acids

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“…6 Doxorubicin (DOX) is a chemotherapy medication used to treat various kinds of cancers, including breast cancer 32 and GC. 33 However, both clinical and fundamental studies have proved that the performance of DOX could be greatly impaired by MDR, especially acquired MDR, after cells have been exposed to a certain dosage of DOX. 34,35 Combination chemotherapy for cancer therapy is considered as an important protocol to enhance therapeutic effects and reduce systemic toxicity by simultaneously modulating multiple cell-signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Quercetin and doxorubicin co-delivery using mesoporous silica nanoparticles enhance the efficacy of gastric carcinoma chemotherapy

Fang

Zhang

Xue

et al. 2018

IJN

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BackgroundEffective gastric carcinoma (GC) chemotherapy is subject to many in vitro and in vivo barriers, such as tumor microenvironment and multidrug resistance.Materials and methodsHerein, we developed a hyaluronic acid (HA)-modified silica nanoparticle (HA-SiLN/QD) co-delivering quercetin and doxorubicin (DOX) to enhance the efficacy of GC therapy (HA-SiLN/QD). The HA modification was done to recognize overexpressed CD44 receptors on GC cells and mediate selective tumor targeting. In parallel, quercetin delivery decreased the expression of Wnt16 and P-glycoprotein, thus remodeling the tumor microenvironment and reversed multidrug resistance to facilitate DOX activity.ResultsExperimental results demonstrated that HA-SiLN/QD was nanoscaled particles with preferable stability and sustained release property. In vitro cell experiments on SGC7901/ADR cells showed selective uptake and increased DOX retention as compared to the DOX mono-delivery system (HA-SiLN/D).ConclusionIn vivo anticancer assays on the SGC7901/ADR tumor-bearing mice model also revealed significantly enhanced efficacy of HA-SiLN/QD than mono-delivery systems (HA-SiLN/Q and HA-SiLN/D).

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“…Excessive ROS and morphological change often impair the MMP [32]. We therefore analyzed the MMP using JC-1.…”

Section: Mitochondrial Membrane Potentialmentioning

confidence: 99%

The combined administration of parthenolide and ginsenoside CK in long circulation liposomes with targeted tLyp-1 ligand induce mitochondria-mediated lung cancer apoptosis

Jin

Zhou

Zhang

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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2018) The combined administration of parthenolide and ginsenoside CK in long circulation liposomes with targeted tLyp-1 ligand induce mitochondria-mediated lung cancer apoptosis, Artificial Cells, Nanomedicine, and Biotechnology, 46:sup3, S931-S942, ABSTRACT Background: Combinations of natural products with low toxicities using tumor-targeting carriers may improve cancer treatment. The combined parthenolide and ginsenoside compound K (CK) within tLyp-1 liposomes, with the aim of improving the efficacy of lung cancer treatment.Results: In vitro studies in A549 human pulmonary adenocarcinoma cells demonstrated that parthenolide/CK tLyp-1 liposomes increased reactive oxygen species levels and induced mitochondrial apoptosis. It enters into cells via receptor-mediated uptake and micropinocytosis, followed by endosomal/lysosomal escape. In vivo studies illustrated that it produced a greater antitumor effect than combined administration of these compounds, with minimal toxicity. Conclusion: The findings of this study indicated that combined application of natural products in nanocarriers could offer attractive therapeutic options.

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VCPA, a novel synthetic derivative of α-tocopheryl succinate, sensitizes human gastric cancer to doxorubicin-induced apoptosis via ROS-dependent mitochondrial dysfunction

Cited by 29 publications

References 46 publications

The Long Noncoding RNA D63785 Regulates Chemotherapy Sensitivity in Human Gastric Cancer by Targeting miR-422a

The Long Noncoding RNA D63785 Regulates Chemotherapy Sensitivity in Human Gastric Cancer by Targeting miR-422a

Quercetin and doxorubicin co-delivery using mesoporous silica nanoparticles enhance the efficacy of gastric carcinoma chemotherapy

The combined administration of parthenolide and ginsenoside CK in long circulation liposomes with targeted tLyp-1 ligand induce mitochondria-mediated lung cancer apoptosis

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