Berberine induces apoptosis by suppressing the arachidonic acid metabolic pathway in hepatocellular carcinoma

Li, Jing; Ou, Li; Kan, Mujie; Zhang, Ming; Shao, Dan; Pan, Yue; Zheng, Huilin; Zhang, Xuewen; Chen, Li; Liu, Song-Yan

doi:10.3892/mmr.2015.3926

Cited by 55 publications

(50 citation statements)

References 28 publications

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“…A recent CE-TOFMS-based metabolomics study suggested that the metabolic profile of DEN model is effective to identify novel biomarkers for early diagnosis of human hepatocellular carcinoma (30). Indeed, inhibition of AA metabolic pathway has been recently reported to associate with the chemoprevention of high fat diet-enhanced colorectal carcinogenesis (41) and the apoptosis of hepatocellular carcinoma cells (42). Furthermore, significantly elevated content of AA was also reported in hepatocellular carcinoma patients compared with the healthy controls (11).…”

Section: Discussionmentioning

confidence: 99%

Metabolome Analyses Uncovered a Novel Inhibitory Effect of Acyclic Retinoid on Aberrant Lipogenesis in a Mouse Diethylnitrosamine-Induced Hepatic Tumorigenesis Model

Qin¹,

Tatsukawa

Hitomi

et al. 2016

Cancer Prevention Research

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Acyclic retinoid (ACR) is a promising drug under clinical trials for preventing recurrence of hepatocellular carcinoma. The objective of this study was to gain insights into molecular basis of the antitumorigenic action of ACR from a metabolic point of view. To achieve this, comprehensive cationic and lipophilic liver metabolic profiling was performed in mouse diethylnitrosamine (DEN)-induced hepatic tumorigenesis model using both capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry. ACR significantly counteracted against acceleration of lipogenesis but not glucose metabolism in DEN-treated mice liver, suggesting an important role of lipid metabolic reprogramming in the initiation step of hepatic tumorigenesis. Knowledge-based pathway analysis suggested that inhibition of linoleic acid metabolites such as arachidonic acid, a proinflammatory precursor, played a crucial role in the prevention by ACR of DEN-induced chronic inflammationmediated tumorigenesis of the liver. As a molecular mechanism of the ACR's effect to prevent the aberrant lipogenesis, microarray analysis identified that a key transcription regulator of both embryogenesis and tumorigenesis, COUP transcription factor 2, also known as NR2F2, was associated with the metabolic effect of ACR in human hepatocellular carcinoma cells. Our study provided potential therapeutic targets for the chemoprevention of hepatocellular carcinoma as well as new insights into the mechanisms underlying prevention of hepatic tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Metabolome Analyses Uncovered a Novel Inhibitory Effect of Acyclic Retinoid on Aberrant Lipogenesis in a Mouse Diethylnitrosamine-Induced Hepatic Tumorigenesis Model

Qin¹,

Tatsukawa

Hitomi

et al. 2016

Cancer Prevention Research

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“…Induction of apoptosis and tumour growth inhibition both in vitro and in vivo. Li et al [37] T47D and MCF7 cell lines.…”

Section: Cell Type or Animal Modelmentioning

confidence: 99%

Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

Habtemariam

2020

Molecules

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Berberine is multifunctional natural product with potential to treat diverse pathological conditions. Its broad-spectrum anticancer effect through direct effect on cancer cell growth and metastasis have been established both in vitro and in vivo. The cellular targets that account to the anticancer effect of berberine are incredibly large and range from kinases (protein kinase B (Akt), mitogen activated protein kinases (MAPKs), cell cycle checkpoint kinases, etc.) and transcription factors to genes and protein regulators of cell survival, motility and death. The direct effect of berberine in cancer cells is however relatively weak and occur at moderate concentration range (10–100 µM) in most cancer cells. The poor pharmacokinetics profile resulting from poor absorption, efflux by permeability-glycoprotein (P-gc) and extensive metabolism in intestinal and hepatic cells are other dimensions of berberine’s limitation as anticancer agent. This communication addresses the research efforts during the last two decades that were devoted to enhancing the anticancer potential of berberine. Strategies highlighted include using berberine in combination with other chemotherapeutic agents either to reduce toxic side effects or enhance their anticancer effects; the various novel formulation approaches which by order of magnitude improved the pharmacokinetics of berberine; and semisynthetic approaches that enhanced potency by up to 100-fold.

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“…BBR altered the viability and apoptosis of HCC cells in a dose-dependent fashion by inducing the translocation of apoptosis-inducing factor between the mitochondria and nucleus. BBR suppressed the levels of cytosolic phospholipase A2 (cPLA) and COX2 which increase the ratio of AA to PEG2 [272]. …”

Section: Introductionmentioning

confidence: 99%

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

McCubrey¹,

Lertpiriyapong²,

Steelman³

et al. 2017

aging

189

128

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Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric (Curcuma longa). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants (e.g., Coptis chinensis) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.

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Berberine induces apoptosis by suppressing the arachidonic acid metabolic pathway in hepatocellular carcinoma

Cited by 55 publications

References 28 publications

Metabolome Analyses Uncovered a Novel Inhibitory Effect of Acyclic Retinoid on Aberrant Lipogenesis in a Mouse Diethylnitrosamine-Induced Hepatic Tumorigenesis Model

Metabolome Analyses Uncovered a Novel Inhibitory Effect of Acyclic Retinoid on Aberrant Lipogenesis in a Mouse Diethylnitrosamine-Induced Hepatic Tumorigenesis Model

Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

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