Curcumin enhances the antitumor effect of ABT-737 via activation of the ROS-ASK1-JNK pathway in hepatocellular carcinoma cells

Ren, Zheng; You, Zhijian; Jia, Jun; Lin, Shunhuan; Han, Shuai; Liu, Aixue; Long, Huidong; Wang, Senming

doi:10.3892/mmr.2015.4715

Cited by 34 publications

(27 citation statements)

References 52 publications

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“…Synergistic Effect of DOX with ABT-199, ABT-263, or ABT-737. In previous reports, ABT-737 and chemotherapeutic agents had the synergistic effect during HCC treatment [32,33]. However, there was not a report of ABT-263 and ABT-199 in the combinational chemotherapy of HCC.…”

Section: Resultsmentioning

confidence: 94%

“…And it also depends on the induction of apoptosis. Moreover, they indicated that activation of the ROS-ASK1-c-Jun N-terminal kinase pathway should be an important factor of the synergy in the combination [33]. Thus, ABT-199, ABT-263, and ABT-737 have potential to be used for screening of more effective drug combinations in treatment of HCC.…”

Section: Introductionmentioning

confidence: 99%

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Doxorubicin and ABT-199 Coencapsulated Nanocarriers for Targeted Delivery and Synergistic Treatment against Hepatocellular Carcinoma

Zhou

Fan

et al. 2019

Journal of Nanomaterials

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For the patients with hepatocellular carcinoma (HCC), conventional chemotherapy is insufficient or has no benefit. Although combination chemotherapy has been proven as an efficient strategy to enhance anti-HCC efficacy, some barriers, such as low bioavailability and side effects, are limiting clinical development. In order to overcome disadvantages of combination chemotherapy in HCC, targeted nanoparticles (NPs) simultaneously loaded with doxorubicin (DOX) and ABT-199 in an optimal synergistic ratio were developed. First, the most synergistic combination with DOX was screened from ABT-199, ABT-263, and ABT-737. Among them, ABT-199 showed optimal synergy with DOX in a ratio of 10 : 1. Then, cationic amphipathic starch (CSaSt) and hyaluronic acid (HA) were used in coencapsulations of those two drugs. Dual-drug synergistic nanoparticles (DDS NPs) were constructed by absorption of DOX NPs around ABT-199 micelles with an optimal ratio via electrostatic interaction. The shape of DDS NPs was similar to a raspberry, and the size was 112 6 ± 13 4 nm. The encapsulation efficiencies of DOX and ABT-199 in DDS NPs were 90 2 ± 4 3% and 94 7 ± 2 8%, respectively; meanwhile, the drug loadings were 1 5 ± 0 4% and 14 1 ± 1 1%, respectively. After 72 h of dialysis, 95% of ABT-199 remained and less than 50% of DOX was released. In vitro investigation showed that the drugs in DDS NPs maintained the treated effect in three HCC cell lines; moreover, DDS NPs could perform intracellular delivery of dual drugs and exhibited continuous release of the drugs into different targets. Low in vivo toxicity was found after the acute toxicity test. In vivo fluorescent imaging revealed that DDS NPs could efficiently target and accumulate in the tumor tissues and be maintained more than 72 h after intravenous injection. Compared with free drugs, DDS NPs with the same dosages exhibited a more significant antitumor effect in the HCC xenograft mouse model. The results indicated that DDS NPs have great potential in HCC chemotherapy.Tables S1 and S2: CI and dose reduction values for inhibition of BEL-7402, SMMC-7721, and Huh-7 by combining DOX with ABT-263 or ABT-737. The synergistic effects of these two combinations were less than combined DOX with . Especially in ABT-263 combined with DOX, it showed few synergy in three HCC cell lines. Figure S1: WST assay results of BEL-7402, SMMC-7721, and Huh-7 cells treated with dual drugs and DDS NPs. As the result show, the toxicity of empty NPs was almost none, and DDS NPs and free dual drugs have equal antiproliferating effect against three HCC cell lines in vitro. The result indicated that the DDS NPs could perform the synergistic anti-HCC effect of ABT-199 combined with DOX. (Supplementary Materials)

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Section: Resultsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Doxorubicin and ABT-199 Coencapsulated Nanocarriers for Targeted Delivery and Synergistic Treatment against Hepatocellular Carcinoma

Zhou

Fan

et al. 2019

Journal of Nanomaterials

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“…ASK1 acts as a serine/threonine protein kinase and participates in multiple biologic processes [43]. Upon accumulation of ROS in cancer cells, ASK1 is activated, leading to apoptotic cell death [25,26,44]. Therefore, ASK1 is a key intermediate in the ROS-dependent pathway of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…We thus demonstrated the importance of the ROS/ASK1 pathway in cytotoxicity of anti-miR-20a and cisplatin co-treatment in CRC. As JNK is an important substrate of ASK1 [26], we next investigated the role of JNK in anti-miR-20a-enhanced cell death. We found that addition of the JNK specific inhibitor SP600125 [27] significantly protected the LoVo cells from cisplatin and anti-miR-20a co-treatment (Fig.…”

Section: Anti-mir-20a Promotes Cisplatin-induced Cytotoxicity In Crc mentioning

confidence: 99%

Knockdown of MiR-20a Enhances Sensitivity of Colorectal Cancer Cells to Cisplatin by Increasing ASK1 Expression

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Platinum-based chemotherapy is one of the most important strategies for treatment of colorectal cancer. To improve the therapeutic efficiency, adjuvant drugs were sought to sensitize colorectal cancer cells to platinum-based agents such as cisplatin. As previous research has shown that miRNAs are associated with chemosensitivity, we aimed to alter miRNA regulation in colorectal cancer cells to increase their chemosensitivity. Methods: MTT assays were performed to determine the viability of HT29, SW480, and LoVo cells. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to examine the expression of miR-20a in these cell lines. Regulation of the miR-20a/ASK1 axis was confirmed by western blotting and luciferase reporter assays. After treatment with miR-20a inhibitor (anti-miR-20a) and cisplatin, production of reactive oxygen species (ROS), mitochondrial membrane potential, and apoptosis were measured by flow cytometry. Activation of ASK1, Bcl-xl, JNK, and caspase-9, -7, and -3 was detected by western blotting. Results: miR-20a was overexpressed in colorectal cancer cell lines. Furthermore, knockdown of miR-20a increased the sensitivity of colorectal cancer cells to cisplatin treatment in vitro and in vivo. We demonstrated that the ASK1 gene was the target of miR-20a, and knockdown of miR-20a increased the expression of ASK1 in colorectal cancer cells. As cisplatin treatment induced production of ROS, knockdown of miR-20a enhanced ROS signaling through promoting the phosphorylation of ASK1. Phosphorylation of JNK and the subsequent mitochondrial apoptosis were triggered by the combination of cisplatin and anti-miR-20a. Conclusions: Knockdown of miR-20a enhanced sensitivity of colorectal cancer cells to cisplatin through the ROS/ASK1/JNK pathway.

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“…Leukemia is one of the leading types of cancer across the globe. In 2014, data collected from United States revealed that total number of leukemia patients was 52,380 in which 30,100 patients were male while 22,280 were females. The number of deaths was as high as 24,090 in which 14,040 were females and 10,050 were males [14].…”

Section: Introductionmentioning

confidence: 99%

Molecular Targets of Curcumin and Future Therapeutic Role in Leukemia

Rafiq¹,

Raza²,

Younas³

et al. 2018

JBM

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Leukemia is a most prevalent type of cancer around the globe. Due to major side effects of Chemotherapy and radiotherapy, scientists worked to explore the alternative source to treat leukemia. An alternative source for the treatment of leukemia existed in the form of curcumin, a natural phenolic compound extracted from curcuma longa plant. It exhibited anticancer properties reducing the tumor load via apoptosis and cell cycle arrested in various cancer cell lines and controlled tumor proliferation by blocking tumor inducing gene such as FLT3, Akt gene, ROS and NF-κB inhibition. At molecular level, curcumin plays a key therapeutic role in protection of normal cells by up regulation of NRF-2 that induces production of cellular antioxidants. It regulates various signaling pathways including NF-KB, JAK/STAT, PI3K/AKT and JNK pathways, thereby affecting cancer initiation, progression, and metastasis. This review described the potential of curcumin for treatment of leukemia; it affects different signaling cascades and their regulation. This study provides a preclinical foundation for future usage of curcumin in the treatment of cancer.

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Curcumin enhances the antitumor effect of ABT-737 via activation of the ROS-ASK1-JNK pathway in hepatocellular carcinoma cells

Cited by 34 publications

References 52 publications

Doxorubicin and ABT-199 Coencapsulated Nanocarriers for Targeted Delivery and Synergistic Treatment against Hepatocellular Carcinoma

Doxorubicin and ABT-199 Coencapsulated Nanocarriers for Targeted Delivery and Synergistic Treatment against Hepatocellular Carcinoma

Knockdown of MiR-20a Enhances Sensitivity of Colorectal Cancer Cells to Cisplatin by Increasing ASK1 Expression

Molecular Targets of Curcumin and Future Therapeutic Role in Leukemia

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