Isatis indigotica Induces Hepatocellular Cancer Cell Death via Caspase-Independent Apoptosis-Inducing Factor Translocation Apoptotic Pathway In Vitro and In Vivo

Chung, Ying-Cheng; Tang, Feng‐Yao; Liao, Jiunn‐Wang; Chung, Chaeuk; Jong, Ting‐Ting; Chen, Shih-Shiung; Tsai, Ching‐Hsiu; Chiang, En‐Pei Isabel

doi:10.1177/1534735410387420

Cited by 21 publications

(12 citation statements)

References 29 publications

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“…Apart from the caspase-dependent apoptotic pathway, there is a caspase-independent apoptotic pathway in which AIF translocates from cytoplasm to nucleus [44,45]. AIF is a flavoprotein inducing DNA damage, chromatin condensation, and DNA degradation [31,46], which is normally present in mitochondria and will translocate into nucleus upon apoptotic induction.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside compound K induces apoptosis in nasopharyngeal carcinoma cells via activation of apoptosis-inducing factor

et al. 2014

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BackgroundNasopharyngeal carcinoma (NPC) has a high incidence rate in Southern China. Although there are conventional therapies, the side effects and toxicities are not always tolerable for patients. Recently, the tumoricidal effect of ginsenosides on different cancer cells has been studied. This study aims to investigate the anti-cancer effect of ginsenosides on NPC cells and their underlying mechanism.MethodsThe cytotoxicity of ginsenosides on NPC cell line HK-1 was measured by MTT assay. Apoptosis was detected by propidium iodide staining followed by flow cytometry. A xenograft tumor model was established by injecting nude mice with HK-1 cells. The activation of caspases and apoptosis-inducing factor (AIF) were evaluated by Western blot analysis. Nuclear translocation of AIF was also studied by immunofluorescence staining. Mitochondrial membrane potential was measured by JC-1 dye using flow cytometry.ResultsFour ginsenosides, 20 (S)-Rh2, compound K (CK), panaxadiol (PD) and protopanaxadiol (PPD), induced apoptotic cell death in HK-1 cells in a concentration-dependent manner. CK inhibited HK-1 xenograft tumor growth most extensively and depleted mitochondrial membrane potential depolarization and induced translocation of AIF from cytoplasm to nucleus in HK-1 cells. In addition, depletion of AIF by siRNA abolished CK-induced HK-1 cell death.ConclusionGinsenoside CK-induced apoptosis of HK-1 cells was mediated by the mitochondrial pathway and could significantly inhibit tumor growth in vivo.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside compound K induces apoptosis in nasopharyngeal carcinoma cells via activation of apoptosis-inducing factor

et al. 2014

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“…Isatis indigotica Fortune has been used in traditional Chinese medicine for more than two millennia and is listed in the Chinese Pharmacopoeia (National Pharmacopoeia Committee, 2010 ). The root and leaves of I. indigotica demonstrate notable anti-viral (Chang et al, 2012 ), anti-inflammatory (Tang et al, 2014 ), anti-tumor (Chung et al, 2011 ), and anti-anaphylaxis (Recio et al, 2006 ) activity, and are used in clinical applications as “Banlengen” and “Daqingye,” respectively. In previous researches, lignans including lariciresinol and larch lignan glycosides were considered as the material base of those activities (Yang et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Gene-to-metabolite network for biosynthesis of lignans in MeJA-elicited Isatis indigotica hairy root cultures

Chen

Tan

et al. 2015

Front. Plant Sci.

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Root and leaf tissue of Isatis indigotica shows notable anti-viral efficacy, and are widely used as “Banlangen” and “Daqingye” in traditional Chinese medicine. The plants' pharmacological activity is attributed to phenylpropanoids, especially a group of lignan metabolites. However, the biosynthesis of lignans in I. indigotica remains opaque. This study describes the discovery and analysis of biosynthetic genes and AP2/ERF-type transcription factors involved in lignan biosynthesis in I. indigotica. MeJA treatment revealed differential expression of three genes involved in phenylpropanoid backbone biosynthesis (IiPAL, IiC4H, Ii4CL), five genes involved in lignan biosynthesis (IiCAD, IiC3H, IiCCR, IiDIR, and IiPLR), and 112 putative AP2/ERF transcription factors. In addition, four intermediates of lariciresinol biosynthesis were found to be induced. Based on these results, a canonical correlation analysis using Pearson's correlation coefficient was performed to construct gene-to-metabolite networks and identify putative key genes and rate-limiting reactions in lignan biosynthesis. Over-expression of IiC3H, identified as a key pathway gene, was used for metabolic engineering of I. indigotica hairy roots, and resulted in an increase in lariciresinol production. These findings illustrate the utility of canonical correlation analysis for the discovery and metabolic engineering of key metabolic genes in plants.

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“…There are only a few herbs which are known to regulate the expression of AIF. Isatis indigotica [44] and polyphyllin D [45] increase the release of AIF from mitochondria, causing apoptosis, while berberine inhibits AIF and therefore suppresses apoptosis [46]. …”

Section: Discussionmentioning

confidence: 99%

Paeonol Protects Memory after Ischemic Stroke via Inhibiting β-Secretase and Apoptosis

Cheng

Tsai³

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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Poststroke dementia commonly occurs following stroke, with its pathogenesis related to β-amyloid production and apoptosis. The present study evaluate the effects of paeonol, one of the phenolic phytochemicals isolated from the Chinese herb Paeonia suffruticosa Andrews (MC), on protection from memory loss after ischemic stroke in the subacute stage. Rats were subjected to transient middle cerebral artery occlusion (tMCAo) with 10 min of ischemia. The data revealed that paeonol recovered the step-through latency in the retrieval test seven days after tMCAo, but did not improve the neurological deficit induced by tMCAo. Levels of Amyloid precursor protein (APP)- and beta-site APP cleaving enzyme (BACE; β-secretase)-immunoreactive cells, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells decreased in the paeonol-administered group. Western blotting revealed decreased levels of Bax protein in mitochondria and apoptosis-inducing factor (AIF) in cytosol following paeonol treatment. In conclusion, we speculate that paeonol protected memory after ischemic stroke via reducing APP, BACE, and apoptosis. Supression the level of Bax and blocking the release of AIF into cytosol might participate in the anti-apoptosis provided by paeonol.

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Isatis indigotica Induces Hepatocellular Cancer Cell Death via Caspase-Independent Apoptosis-Inducing Factor Translocation Apoptotic Pathway In Vitro and In Vivo

Cited by 21 publications

References 29 publications

Ginsenoside compound K induces apoptosis in nasopharyngeal carcinoma cells via activation of apoptosis-inducing factor

Ginsenoside compound K induces apoptosis in nasopharyngeal carcinoma cells via activation of apoptosis-inducing factor

Gene-to-metabolite network for biosynthesis of lignans in MeJA-elicited Isatis indigotica hairy root cultures

Paeonol Protects Memory after Ischemic Stroke via Inhibiting β-Secretase and Apoptosis

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