Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the VEGFR2/Src/FAK Pathway

Chung-Yu, Ku; Ying-Ren, Wang; H, Lin; Lu, Shao‐Chun; Lin, Jung‐Yaw

doi:10.1371/journal.pone.0126725

Cited by 48 publications

(47 citation statements)

References 37 publications

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“…The principal compounds are triterpenes, which exhibit remarkable anticancer effects in HCC [7–9]. Other compounds have also shown cytotoxic activity including the phenolic constituents and isomeric flavonoids [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9

Hou

Wang

et al. 2017

Oncotarget

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Actinidia chinensis Planch root extract (acRoots) is a traditional Chinese medicine with anti-tumor efficacy. To investigate the mechanisms responsible for this activity, we examined the effects of acRoots on cholesterol metabolism in hepatocellular carcinoma (HCC). mRNA chip analysis was used to identify the metabolic genes regulated by acRoots. The effects of acRoots on cholesterol synthesis and uptake were evaluated by measuring intracellular cholesterol levels and 3,3′-dioctadecylindocarbocyanine-labeled low-density lipoprotein (Dil-LDL) uptake. Expression of metabolic genes was analyzed using quantitative reverse transcription PCR, western blotting, and flow cytometry. acRoots reduced the viability of LM3 and HepG2 cells at 5 mg/mL and HL-7702 cells at 30 mg/mL. Gene expression profiling revealed that treatment with acRoots altered expression of genes involved in immune responses, inflammation, proliferation, cell cycle control, and metabolism. We also confirmed that acRoots enhances expression of PCSK9, which is important for cholesterol metabolism. This resulted in decreased LDL receptor expression, inhibition of LDL uptake by LM3 cells, decreased total intracellular cholesterol, and reduced proliferation. These effects were promoted by PCSK9 overexpression and rescued by PCSK9 knockdown. Our data demonstrate that acRoots is a novel anti-tumor agent that inhibits cholesterol metabolism though a PCSK9-mediated signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9

Hou

Wang

et al. 2017

Oncotarget

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“…Corosolic acid, a natural triterpenoid compound derived from banaba leaves and apples, has been shown to have anti-tumor effects on a variety of tumor models, such as glioblastoma 118 , prostate cancer 119,120 , retinoblastoma 121 , renal carcinoma 122 , gastric cancer 123 , breast cancer 124 , liver cancer 125,126 , colon cancer 127 , lung adenocarcinoma 128 , cervix adenocarcinoma 129 , osteosarcoma 130,131 . Similar to curcumin and resveratrol, CA is a potent STAT3 inhibitor, suppressing cell growth of ovarian cancer and glioblastoma by abrogating STAT3 activity 118,132 .…”

Section: Corosolic Acidmentioning

confidence: 99%

STAT3 signaling in ovarian cancer: a potential therapeutic target

Liang¹,

Chen²,

Chen³

et al. 2020

J. Cancer

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Accumulating evidence has shown that Signal Transducer and Activator of Transcription 3 (STAT3) is thought to be a promising target for cancer therapy as STAT3 is frequently overexpressed in a wide range of cancer cells as well as clinical specimens, promoting tumor progression. It is widely accepted that STAT3 regulates a variety of cellular processes, such as tumor cell growth, survival, invasion, cancer stem cell-like characteristic, angiogenesis and drug-resistance. In this review, we focus on the role of STAT3 in tumorigenesis in ovarian cancer and discuss the existing inhibitors of STAT3 signaling that can be promisingly developed as the strategies for ovarian cancer therapy.

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“…An in vivo mouse model showed that Corosolic acid exhibited a significant effect on tumor growth with a relative low dose. Ku et al [34] further demonstrated that the combination of Corosolic acid and sorafenib can synergistically affect tumor growth with a wide range of concentrations.…”

Section: Clinical Experience With Inhibitors Of Src Signalingmentioning

confidence: 99%

Role and inhibition of Src signaling in the progression of liver cancer

et al. 2016

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During 2012, about 782,500 new liver cancer cases were diagnosed and 745,500 deaths occurred all around the world. Liver cancer is the 2nd major cause of cancer death in men around the world and in underdeveloped countries. Dysregulation of the balance between proliferation and cell death, hepatitis B virus infection and hepatitis C virus chronic infection, and carcinogenic micro RNAs mainly contribute to the development and progression of liver cancer. Under physiological status, Src maintained the foundation of cells. While in liver cancer, it is known that the basic activities of cells are apparently disturbed possibly by Src. The mechanisms underlying the development and progression of liver cancer is needed to elucidate. In this study, we summarized newly found regulation pathway of SRC signaling, and clinical experience with inhibitors of Src signaling, such as, novel molecules that directly or indirectly targeted Src signaling which can be utilized in the treatment of liver cancer.

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Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the VEGFR2/Src/FAK Pathway

Cited by 48 publications

References 37 publications

Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9

Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9

STAT3 signaling in ovarian cancer: a potential therapeutic target

Role and inhibition of Src signaling in the progression of liver cancer

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