Carnosic acid induces apoptosis of hepatocellular carcinoma cells via ROS-mediated mitochondrial pathway

Zhang, Xinrui; Cai, Guangsheng; Li, Xin; Wang, Di

doi:10.1016/j.cbi.2017.09.005

Cited by 46 publications

(41 citation statements)

References 37 publications

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“…ROS participates in many intracellular pathological changes 6, 7. In accord with our and other previous studies, ROS triggers programmed cell death through the mitochondrial pathway, death receptor pathway, and endoplasmic reticulum stress‐mediated pathway 8, 9, 10. Previous studies indicated that AGEs induced endothelial cell apoptosis by exacerbating ROS‐mediated apoptosis 11…”

Section: Introductionsupporting

confidence: 91%

“…6,7 In accord with our and other previous studies, ROS triggers programmed cell death through the mitochondrial pathway, death receptor pathway, and endoplasmic reticulum stress-mediated pathway. [8][9][10] Previous studies indicated that AGEs induced endothelial cell apoptosis by exacerbating ROSmediated apoptosis. 11 Activation of antioxidant response element (ARE) is believed to be a modulator of the intracellular antioxidant defense system, which protects against ROS-mediated cell death.…”

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confidence: 99%

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Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

Liu

Zhang

et al. 2017

JAHA

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BackgroundThe matrine‐type alkaloids are bioactive components extracted from Sophora flavescens, which is used in treatment of diabetes mellitus in traditional Chinese medicine. Advanced glycation end products mediate diabetic vascular complications. This study was aimed to investigate the protective effects and molecular mechanisms of matrine‐type alkaloids on advanced glycation end products–induced reactive oxygen species–mediated endothelial apoptosis.Methods and ResultsRats aorta and cultured rat aortic endothelial cells were exposed to advanced glycation end products. Matrine‐type alkaloids, p38 mitogen‐activated protein kinase (MAPK) inhibitor, and small interference RNAs against p38 MAPK kinases MAPK kinase kinase (MKK)3 and MKK6 were administrated. Intracellular reactive oxygen species production, cell apoptosis, phosphorylation of MKKs/p38 MAPK, and expression levels of heme oxygenase/NADPH quinone oxidoreductase were assessed. The nuclear factor erythroid 2‐related factor 2 nuclear translocation and the binding activity of nuclear factor erythroid 2‐related factor 2 with antioxidant response element were also evaluated. Matrine‐type alkaloids suppressed intracellular reactive oxygen species production and inhibited endothelial cell apoptosis in vivo and in vitro by recovering phosphorylation of MKK3/6 and p38 MAPK, nuclear factor erythroid 2‐related factor 2 nuclear translocation, and antioxidant response element binding activity, as well as the expression levels of heme oxygenase/NADPH quinone oxidoreductase. p38 MAPK inhibitor treatment impaired the effects of matrine‐type alkaloids in vivo and in vitro. MKK3/6 silencing impaired the effects of matrine‐type alkaloids in vitro.ConclusionsMatrine‐type alkaloids exert endothelial protective effects against advanced glycation end products induced reactive oxygen species–mediated apoptosis by targeting MKK3/6 and enhancing their phosphorylation.

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Section: Introductionsupporting

confidence: 91%

mentioning

confidence: 99%

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

Liu

Zhang

et al. 2017

JAHA

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“…Many scientific studies have shown that CA has anti-inflammatory, antioxidant, and anti-carcinogenic activities. Specifically, carnosic acid could inhibit cancer progression by inducing apoptosis in cancer cells through stimulating the production of reactive oxygen species (ROS) and promoting the Caspase-3 signaling pathway 58,59 . Some researchers believe that CA also reduces cancer cell viability through the inactivation of STAT3 signaling and AKT/mTOR pathway 60,61 .…”

Section: Discussionmentioning

confidence: 99%

BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression

Elsarraj

Limback

et al. 2020

npj Breast Cancer

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The molecular processes by which some human ductal carcinoma in situ (DCIS) lesions advance to the more aggressive form, while others remain indolent, are largely unknown. Experiments utilizing a patient-derived (PDX) DCIS Mouse INtraDuctal (MIND) animal model combined with ChIP-exo and RNA sequencing revealed that the formation of protein complexes between B Cell Lymphoma-9 (BCL9), phosphoserine 727 STAT3 (PS-727-STAT3) and non-STAT3 transcription factors on chromatin enhancers lead to subsequent transcription of key drivers of DCIS malignancy. Downregulation of two such targets, integrin β3 and its associated metalloproteinase, MMP16, resulted in a significant inhibition of DCIS invasive progression. Finally, in vivo targeting of BCL9, using rosemary extract, resulted in significant inhibition of DCIS malignancy in both cell line and PDX DCIS MIND animal models. As such, our studies provide compelling evidence for future testing of rosemary extract as a chemopreventive agent in breast cancer.npj Breast Cancer (2020) 6:12 ; https://doi.

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“…Histopathological examination. The liver, spleen and kidney tissues were fixed in 4% paraformaldehyde and subjected to histopathological examination using hematoxylin and eosin staining, as described in our previous study (15).…”

Section: Mcf-7mentioning

confidence: 99%

“…One such compound is 18-β-glycyrrhetinic acid, which is mainly obtained from Glycyrrhiza plants and displays pro-apoptotic properties in pituitary adenoma cells via the regulation of ROS and mitogen-activated protein kinases (MAPKs) (14). It has also been reported that carnosic acid induces the apoptosis of hepatocellular carcinoma cells via an ROS-mediated mitochondrial apoptosis pathway (15). Astilbin is a flavonoid that is commonly found in various herbal medicines and foods, such as Smilax glabra Roxb., Sarcandra glabra (Thunb.)…”

Section: Introductionmentioning

confidence: 99%

Caspase-dependent mitochondrial apoptotic pathway is involved in astilbin-mediated cytotoxicity in breast carcinoma cells

Sun¹,

Zhang²,

Zhang³

et al. 2018

Oncol Rep

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Astilbin exhibits several pharmacological activities, including hypoglycemic, anti-oxidant and anti-inflammatory properties. The aim of the present study was to investigate the pro-apoptotic activities of astilbin on breast cancer in cells and mice. It was demonstrated that astilbin significantly reduced the cell viability, increased the cell apoptosis rate, suppressed the migration ability, caused the dissipation of the mitochondrial membrane potential and induced the overaccumulation of intracellular reactive oxygen species in MCF-7 and MDA-MB-231 cells after 12 or 24 h of exposure. Data obtained from western blotting suggested that astilbin suppressed the expression levels of B-cell lymphoma 2 (Bcl-2), while it increased the expression levels of cleaved caspase-3, -8 and -9, and Bcl-2-associated X protein in breast carcinoma cells. Furthermore, astilbin inhibited the growth of MCF-7-xenografted tumors in nude mice without influencing their bodyweights or organ (liver, spleen and kidney) functions. Additionally, astilbin enhanced the expression of pro-apoptotic proteins and suppressed the expression of anti-apoptotic proteins in tumor tissues. All these results revealed that astilbin exhibits pro-apoptotic properties in breast carcinoma cells via modulation of the caspase-dependent pathway, which highlights the feasibility of astilbin as a candidate agent for breast cancer treatment.

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Carnosic acid induces apoptosis of hepatocellular carcinoma cells via ROS-mediated mitochondrial pathway

Cited by 46 publications

References 37 publications

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression

Caspase-dependent mitochondrial apoptotic pathway is involved in astilbin-mediated cytotoxicity in breast carcinoma cells

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