Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling

Yang, Guang; Yuan, Yuhui; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

doi:10.1016/j.bbrc.2017.03.139

Cited by 49 publications

(40 citation statements)

References 34 publications

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“…Recently, Lee and colleagues reported that aspirin prevented the development of HCC [43]. We previously reported that aspirin suppressed the abnormal lipid metabolism in hepatoma cells [21]. However, whether aspirin could regulate the glucose metabolism in suppression of liver cancer is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Long-term follow-up study in several trials demonstrates that the nonsteroid anti-inflammatory agent aspirin prevents the development of HCC, colorectal adenomas, breast and pancreatic cancers [14,[17][18][19][20]. Our group has reported that aspirin is capable of suppressing the abnormal lipid metabolism in HCC cells [21]. In addition, aspirin treatment also resulted in a reduction in basal rates of glucose production and an improvement in insulin-stimulated peripheral glucose uptake under matched plasma insulin concentrations during the clamp [22].…”

Section: Introductionmentioning

confidence: 95%

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Aspirin inhibits the proliferation of hepatoma cells through controlling GLUT1-mediated glucose metabolism

et al. 2018

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Aspirin can efficiently inhibit liver cancer growth, but the mechanism is poorly understood. In this study, we report that aspirin modulates glucose uptake through downregulating glucose transporter 1 (GLUT1), leading to the inhibition of hepatoma cell proliferation. Our data showed that aspirin significantly decreased the levels of reactive oxygen species (ROS) and glucose consumption in hepatoma cells. Interestingly, we identified that GLUT1 and HIF1α could be decreased by aspirin. Mechanically, we demonstrated that the -1008/-780 region was the regulatory element of transcriptional factor NF-κB in GLUT1 promoter by luciferase report gene assays. PDTC, an inhibitor of NF-κB, could suppress the expression of GLUT1 in HepG2 and H7402 cells, followed by affecting the levels of ROS and glucose consumption. CoCl-activated HIF1α expression could slightly rescue the GLUT1 expression inhibited by aspirin or PDTC, suggesting that aspirin depressed GLUT1 through targeting NF-κB or NF-κB/HIF1α signaling. Moreover, we found that GLUT1 was highly expressed in clinical HCC tissues relating to their paired adjacent normal tissues. Importantly, we observed that high level of GLUT1 was significantly correlated with the poor relapse-free survival of HCC patients by analysis of public data. Functionally, overexpression of GLUT1 blocked the PDTC-induced or aspirin-induced inhibition of glucose metabolism in HepG2 cells. Conversely, aspirin failed to work when GLUT1 was stably knocked down in the cells. Administration of aspirin could depress the growth of hepatoma cells through controlling GLUT1 in vitro and in vivo. Thus, our finding provides new insights into the mechanism by which aspirin depresses liver cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Aspirin inhibits the proliferation of hepatoma cells through controlling GLUT1-mediated glucose metabolism

et al. 2018

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“…In light of these reported findings, we attempted to uncover the differences in signaling after each treatment. Fatty acids are the main substrates for energy production and membrane biogenesis; the shift in the lipid acquisition mechanism from lipid uptake toward de novo lipogenesis dramatically changes the membrane properties and protects cells from both endogenous and exogenous injury, thus maintaining tumorigenesis [37].…”

Section: Discussionmentioning

confidence: 99%

Compound C enhances the anticancer effect of aspirin in HER-2-positive breast cancer by regulating lipid metabolism in an AMPK-independent pathway

Wu¹,

Yan²,

Xu³

et al. 2020

Int. J. Biol. Sci.

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Various clinical studies have determined that aspirin shows anticancer effects in many human malignant cancers, including human epidermal growth factor receptor-2 (HER-2)-positive breast cancer. However, the anti-tumor mechanism of aspirin has not been fully defined. The aim of this study was to determine the role of Compound C in enhancing the anticancer effect of aspirin. HER-2-positive breast cancer cell lines were treated with aspirin with or without Compound C pre-treatment; their phenotypes and mechanisms were then analyzed in vitro and in vivo. Aspirin exhibited anticancer effects in HER-2-positive breast cancer by inhibiting cell growth and inducing apoptosis through the activation of AMP-activated protein kinase (AMPK). Unexpectedly, pre-treatment with Compound C, a widely used AMPK inhibitor, induced robust anticancer effects in cells compared to aspirin monotherapy. This anticancer effect was not distinct in HER-2 negative breast cancer MDA-MB-231 cells and may be due to the inhibition of lipid metabolism mediated by c-myc. Besides, c-myc re-expression or palmitic acid supply could partially restored cell proliferation. Aspirin exhibits anticancer effects in HER-2-positive breast cancer by regulating lipid metabolism mediated by c-myc, and Compound C strengthens these effects in an AMPK-independent manner. Our results potentially provide a novel therapeutic strategy exploiting combined aspirin and Compound C therapy for HER-2-positive breast cancer, which acts by reducing de novo lipid synthesis.

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“…In our study, the values of total and HDL cholesterol was higher in patients without DM2 taking ASA, while glucose and triglycerides were higher in DM2 patients not on ASA treatment. This is a possible consequence of ASA intake, which lowers plasma triglycerides (25) and suppresses the abnormal lipid metabolism (26). Higher levels of HDL cholesterol in nondiabetic patients taking ASA can also be related to the fact that diabetic patients have significantly lower levels of HDL than nondiabetic patients (27).…”

Section: Discussionmentioning

confidence: 99%

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients

et al. 2018

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Abstract. Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non-diabetic patients, have an inhibitory effect on cancer cell survival. The present population-based study conducted in the province of Trieste (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients. All permanent residents diagnosed with a CRC between 2004 and 2007 were ascertained through the regional health information system. CRC-specific and relative survival probabilities were computed for each group of patients defined by CRC stage, presence or absence of DM2 treated with metformin, and presence or absence of daily ASA therapy. A total of 515 CRC patients without DM2 and 156 with DM2 treated with metformin were enrolled in the study. At the time of CRC diagnosis, 71 (14%) nondiabetic and 39 (25%) diabetic patients were taking ASA daily. The five-year relative survival for stage III CRC was 101% [95% confidence interval (CI) =76-126] in the 18 patients with DM2 treated with metformin and ASA, 55% (95% CI=31-78) in the 23 without DM2 treated with ASA, 55% (95% CI=45-65) in the 150 without DM2 not taking ASA, and 29% (95% CI=13-45) in the 43 with DM2 treated with metformin, however not with ASA. The findings support the hypothesis of a possible inhibitory effect of metformin and ASA on CRC cells. Randomized controlled trials are required to verify this hypothesis.

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Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling

Cited by 49 publications

References 34 publications

Aspirin inhibits the proliferation of hepatoma cells through controlling GLUT1-mediated glucose metabolism

Aspirin inhibits the proliferation of hepatoma cells through controlling GLUT1-mediated glucose metabolism

Compound C enhances the anticancer effect of aspirin in HER-2-positive breast cancer by regulating lipid metabolism in an AMPK-independent pathway

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients

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