Plumbagin Inhibits Expression of Virulence Factors and Growth of Helicobacter pylori
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Helicobacter pylori primarily colonizes the human stomach. Infection by this bacterium is associated with various gastric diseases, including inflammation, peptic ulcer, and gastric cancer. Although there are antibiotic regimens for the eradication of H. pylori, the resistance of this species against antibiotics has been continuously increasing. The natural compound plumbagin has been reported as an antimicrobial and anticancer molecule. In this study, we analyzed the inhibitory effect of plumbagin on H. pylori strain ATCC 49503 as well as the expression of various molecules associated with H. pylori growth or virulence by immunoblotting and reverse transcription polymerase chain reaction (RT-PCR) analyses. We demonstrated the minimal inhibitory concentration of plumbagin on H. pylori through the agar dilution and broth dilution methods. Furthermore, we investigated the effect of plumbagin treatment on the expression of the RNA polymerase subunits and various virulence factors of H. pylori. Plumbagin treatment decreased the expression of RNA polymerase subunit alpha (rpoA), which is closely associated with bacterial survival. Moreover, the mRNA and protein levels of the major CagA and VacA toxins were decreased in plumbagintreated H. pylori cells. Likewise, the expression levels of urease subunit alpha (ureA) and an adhesin (alpA) were decreased by plumbagin treatment. Collectively, these results suggest that plumbagin may inhibit the growth, colonization, and pathogenesis of H. pylori by the mechanism demonstrated in this study.
Abstract
Helicobacter pylori primarily colonizes the human stomach. Infection by this bacterium is associated with various gastric diseases, including inflammation, peptic ulcer, and gastric cancer. Although there are antibiotic regimens for the eradication of H. pylori, the resistance of this species against antibiotics has been continuously increasing. The natural compound plumbagin has been reported as an antimicrobial and anticancer molecule. In this study, we analyzed the inhibitory effect of plumbagin on H. pylori strain ATCC 49503 as well as the expression of various molecules associated with H. pylori growth or virulence by immunoblotting and reverse transcription polymerase chain reaction (RT-PCR) analyses. We demonstrated the minimal inhibitory concentration of plumbagin on H. pylori through the agar dilution and broth dilution methods. Furthermore, we investigated the effect of plumbagin treatment on the expression of the RNA polymerase subunits and various virulence factors of H. pylori. Plumbagin treatment decreased the expression of RNA polymerase subunit alpha (rpoA), which is closely associated with bacterial survival. Moreover, the mRNA and protein levels of the major CagA and VacA toxins were decreased in plumbagintreated H. pylori cells. Likewise, the expression levels of urease subunit alpha (ureA) and an adhesin (alpA) were decreased by plumbagin treatment. Collectively, these results suggest that plumbagin may inhibit the growth, colonization, and pathogenesis of H. pylori by the mechanism demonstrated in this study.
참고문헌 (35)
- Borin BN, "Helicobacter pylori RNA polymerase alpha-subunit C-terminal domain shows features unique to varepsilon-proteobacteria and binds NikR", DNA complexes, 2014, pp.23, 454~463
- Bornschein J, "Helicobacter pylori and gastric cancer", Dig. Dis, 32, pp.249~264 (2014)
- Cover TL, "Helicobacter pylori VacA, a paradigm for toxin multifunctionality", Nat. Rev. Microbiol, 3, pp.320~332 (2005)
- Cover TL, "Helicobacter pylori in health and disease", Gastroenterology, 136, pp.1863~1873 (2009)
- Dailidiene D, "Urea sensitization caused by separation of Helicobacter pylori RNA polymerase beta and beta' subunits", Helicobacter, 12, pp.103~111 (2007)
- de Paiva SR, "Antimicrobial activity in vitro of plumbagin isolated from Plumbago species", Mem. Inst. Oswaldo. Cruz, 98, pp.959~961 (2003)
- Eldhose B, "Plumbagin reduces human colon cancer cell survival by inducing cell cycle arrest and mitochondria-mediated apoptosis", Int. J. Oncol, 45, pp.1913~1920 (2014)
- Ghotaslou R, "Prevalence of antibiotic resistance in Helicobacter pylori: A recent literature review", World J. Methodol, 5, pp.164~174 (2015)
- Hatakeyama M, "Oncogenic mechanisms of the Helicobacter pylori CagA protein", Nat. Rev. Cancer, 4, pp.688~694 (2004)
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, "Schistosomes, liver flukes and Helicobacter pylori", IARC Monogr. Eval. Carcinog. Risks Hum, 61, pp.1~241 (1994)
- Kaewbumrung S, "Antibacterial activity of plumbagin derivative-rich Plumbago indica root extracts and chemical stability", Nat. Prod. Res, 28, pp.835~837 (2014)
- Kalali B, "H. pylori virulence factors: influence on immune system and pathology", Mediators Inflamm, 2014, pp.426309~ (2014)
- Khaw AK, "Plumbagin alters telomere dynamics, induces DNA damage and cell death in human brain tumour cells", Mutat. Res. Genet. Toxicol. Environ. Mutagen, 793, pp.86~95 (2015)
- Kim SH, "Inhibitory effects of anthocyanins on secretion of Helicobacter pylori CagA and VacA toxins", Int. J. Med. Sci, 9, pp.838~842 (2012)
- Kimura M, "Functional map of the alpha subunit of Escherichia coli RNA polymerase: insertion analysis of the amino-terminal assembly domain", J. Mol. Biol, 248, pp.756~767 (1995)
- Krajewska B, "Ureases I. Functional, catalytic and kinetic properties: A review", J. Mol. Catal B Enzym, 59, pp.9~21 (2009)
- Lee JW, "Prevalence of primary and secondary antimicrobial resistance of Helicobacter pylori in Korea from 2003 through 2012", Helicobacter, 18, pp.206~214 (2013)
- 이상욱, "Treatment of Helicobacter pylori Infection in Korea: A Systematic Review and Meta-analysis", Journal of Korean Medical Science, 30(8), pp.1001~1009 (2015), 대한의학회
- Li YC, "Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K", Akt, Cancer Lett, pp.2014, 344[DOI]
- Mathew R, "The evolving story of the omega subunit of bacterial RNA polymerase", Trends Microbiol, 14, pp.450~455 (2006)
- Nakayama M, "Helicobacter pylori VacA-induced inhibition of GSK3 through the PI3K", Akt signaling pathway, 2009, pp.284, 1612~1619
- Nitharwal RG, "Helicobacter pylori chromosomal DNA replication: current status and future perspectives", FEBS Lett, 585, pp.7~17 (2011)
- Odenbreit S, "Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion", Science, 287, pp.1497~1500 (2000)
- Padhye S, "Perspectives on medicinal properties of plumbagin and its analogs", Med. Res. Rev, 32, pp.1131~1158 (2012)
- Park BS, "Antibacterial activity of Tabebuia impetiginosa Martius ex DC (Taheebo) against Helicobacter pylori", J. Ethnopharmacol, 105, pp.255~262 (2006)
- Saadat I, "Helicobacter pylori CagA targets PAR1", MARK kinase to disrupt epithelial cell polarity, 2007, pp.447, 330~333
- Smolka AJ, "How Helicobacter pylori infection controls gastric acid secretion", J. Gastroenterol, 47, pp.609~618 (2012)
- Solnick JV, "The major sigma factor (RpoD) from Helicobacter pylori and other gram-negative bacteria shows an enhanced rate of divergence", J. Bacteriol, 179, pp.6196~6200 (1997)
- Stein M, "c-Src", Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs, 2002, pp.43, 971~980
- Sunil C, "Antidiabetic effect of plumbagin isolated from Plumbago zeylanica L. root and its effect on GLUT4 translocation in streptozotocininduced diabetic rats", Food Chem. Toxicol, 50, pp.4356~4363 (2012)
- Terradot L, "Structural insight into Helicobacter pylori DNA replication initiation", Gut. Microbes, 1, pp.330~334 (2010)
- Wang YC, "High-performance liquid chromatography for quantification of plumbagin, an anti-Helicobacter pylori compound of Plumbago zeylanica L", J. Chromatogr A, 1094, pp.99~104 (2005)
- Wiedemann T, "Helicobacter pylori cag-Pathogenicity islanddependent early immunological response triggers later precancerous gastric changes in Mongolian gerbils", PLoS One, 4, pp.e4754~ (2009)
- Wu IT, "Five-year sequential changes in secondary antibiotic resistance of Helicobacter pylori in Taiwan", World J. Gastroenterol, 21, pp.10669~10674 (2015)
- Zhang YX, "Primary antibiotic resistance of Helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: a prospective serial study", World J. Gastroenterol, 21, pp.2786~2792 (2015)