Capsaicin Induces Heme Oxygenase-1 Expression in HepG2 Cells<i>Via</i>Activation of PI3K-Nrf2 Signaling: NAD(P)H:Quinone Oxidoreductase as a Potential Target

Joung, Eun-Joo; Li, Meihua; Lee, Hee Geum; Somparn, Nuntiya; Jung, Young Suk; Na, Hye-Kyung; Kim, Sung Hoon; Cha, Young‐Nam; Surh, Young‐Joon

doi:10.1089/ars.2007.1827

Cited by 112 publications

(78 citation statements)

References 32 publications

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“…HO-1 is highly induced by oxidative stress, as well as a wide range of dietary antioxidants, such as a-lipoic acid found in broccoli and spinach, resveratrol found in grapes and isothiocyanates from brassica vegetables, according to in vitro and in vivo experiments (78)(79)(80)(81)(82). The higher exposure to exogenous antioxidants from higher intake of vegetables and fruits could increase the expression and activity of HO-1, particularly among participants who have the wild-type shorter promoters, thereby increasing its protective function in various tissues.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk

Li¹,

Ambrosone²,

McCullough

et al. 2009

Carcinogenesis

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Dietary antioxidants may interact with endogenous sources of pro-and antioxidants to impact breast cancer risk. A nested case-control study of postmenopausal women (505 cases and 502 controls) from the Cancer Prevention Study-II Nutrition Cohort was conducted to examine the interaction between oxidative stress-related genes and level of vegetable and fruit intake on breast cancer risk. Genetic variations in catalase (CAT) (C2262T), myeloperoxidase (MPO) (G2463A), endothelial nitric oxide synthase (NOS3) (G894T) and heme oxygenase-1 (HO-1) [(GT) n dinucleotide length polymorphism] were not associated with breast cancer risk. Women carrying the low-risk CAT CC [odds ratio (OR) 5 0.75, 95% confidence interval (CI) 0.50-1.11], NOS3 TT (OR 5 0.54, 95% CI 5 0.26-1.12, P-trend 5 0.10) or HO-1 S allele and MM genotype (OR 5 0.56, 95% CI 5 0.37-0.55), however, were found to be at non-significantly reduced breast cancer risk among those with high vegetable and fruit intake ( ‡median; P-interactions 5 0.04 for CAT, P 5 0.005 for NOS3 and P 5 0.07 for HO-1). Furthermore, those with ‡4 putative low-risk alleles in total had significantly reduced risk (OR 5 0.53, 95% CI 5 0.32-0.88, P-interaction 5 0.006) compared with those with £2 low-risk alleles. In contrast, among women with low vegetable and fruit intake (< median), the low-risk CAT CC (OR 5 1.33, 95% CI 5 0.89-1.99), NOS3 TT (OR 5 2.93, 95% CI 5 1.38-6.22) and MPO AA (OR 5 2.09, 95% CI 5 0.73-5.95) genotypes appeared to be associated with raised breast cancer risk, with significantly increased risks observed in those with ‡4 low-risk alleles compared with participants with £2 low-risk alleles (OR 5 1.77, 95% CI 5 1.05-2.99, P-interaction 5 0.006). Our results support the hypothesis that there are joint effects of endogenous and exogenous antioxidants.

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Section: Discussionmentioning

confidence: 99%

Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk

Li¹,

Ambrosone²,

McCullough

et al. 2009

Carcinogenesis

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“…Under the Nrf2 activation, it dissociates from Kelch-like ECHassociated protein 1 (Keap1) and translocates into the nucleus, where it binds ARE (18). Different pathways may activate Nrf2, including PI3K/Akt and MAPKs (6,13,38). We found that EP can activate Nrf2 by enhancing Nrf2 nuclear accumulation and the ARE-luciferase activity.…”

mentioning

confidence: 82%

Ethyl Pyruvate Induces Heme Oxygenase-1 Through p38 Mitogen-Activated Protein Kinase Activation by Depletion of Glutathione in RAW 264.7 Cells and Improves Survival in Septic Animals

Jang

Kim

Tsoyi

et al. 2012

Antioxidants & Redox Signaling

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Aims: We investigated the molecular mechanism by which ethyl pyruvate (EP) induces heme oxygenase-1 (HO-1) in RAW 264.7 cells and its effect on survival rate in cecal ligation and puncture (CLP)-induced wild-type (WT) and HO-1 knockout (HO-1 -/ -) septic mice. Results: EP induced HO-1 in a dose-and time-dependent manner, which was mediated through p38 mitogen-activated protein kinase (MAPK) and NF-E2-related factor 2 (Nrf2) signaling cascade in RAW 264.7 cells. EP significantly inhibited the lipopolysaccharide (LPS)-stimulated inducible nitric oxide synthase (iNOS) expression and high-mobility group box 1 (HMGB1) release in RAW 264.7 cells. The inhibitory effect of EP on LPS-stimulated iNOS expression and HMGB1 release was reversed by transfection with siHO-1RNA in RAW 264.7 cells, but EP failed to reduce them in HO-1 -/ -peritoneal macrophages treated with LPS. Moreover, treatment of cells with glutathione ethyl ester (GSH-Et), SB203580 (p38 MAPK inhibitor), siHO-1, or p38-siRNA transfection inhibited anti-inflammatory effect of EP. Interestingly, both HO-1 induction and phosphorylation of p38 by EP were reversed by GSH-Et, and antioxidant redox elementluciferase activity by EP was reversed by SB203580 in LPS-activated cells. EP increased survival and decreased serum HMGB1 in CLP-WT mice, whereas it did not increase survival or decrease circulating HMGB1 in HO-1 -/ -CLP-mice. Innovation and Conclusion: Our work provides new insights into the understanding the molecular mechanism by showing that EP induces HO-1 through a p38 MAPK-and NRF2-dependent pathway by decreasing GSH cellular levels. We conclude that EP inhibits proinflammatory response to LPS in macrophages and increases survival in CLP-induced septic mice by upregulation of HO-1 level, in which p38 MAPK and Nrf2 play an important role. Antioxid. Redox Signal. 17, 878-889.

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“…Capsaicin induced apoptosis in the hepatocellular carcinoma cell line HepG2 with the involvement of intracellular Ca 2+ , ROS, Bcl-2 family, cytochrome c protein expression, and caspase-3 activity (Huang et al 2009). In the same cells, capsaicin increased ROS production and induced expression of heme oxygenase-1 (HO-1) (Lee et al 2004;Joung et al 2007). Likewise, capsaicin sensitized hepatocellular carcinoma cells as well as breast cancer cells and leukemia cells to apoptosis induced by tumor necrosis factor-related, apoptosis-inducing ligand (TRAIL) (Moon et al 2012).…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

The Potential Antitumor Effects of Capsaicin

Díaz‐Laviada

Rodríguez-Henche

2014

Capsaicin as a Therapeutic Molecule

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Capsaicin, one of the major pungent ingredients found in red peppers, has been recently demonstrated to induce apoptosis in many types of malignant cell lines including colon adenocarcinoma, pancreatic cancer, hepatocellular carcinoma, prostate cancer, breast cancer, and many others. The mechanism whereby capsaicin induces apoptosis in cancer cells is not completely elucidated but involves intracellular calcium increase, reactive oxygen species generation, disruption of mitochondrial membrane transition potential, and activation of transcription factors such as NFκB and STATS. Recently, a role for the AMP-dependent kinase (AMPK) and autophagy pathways in capsaicin-triggered cell death has been proposed. In addition, capsaicin shows antitumor activity in vivo by reducing the growth of many tumors induced in mice. In this chapter, we report the last advances performed in the antitumor activity of capsaicin and review the main signaling pathways involved. CapsaicinCapsaicin (8-methyl-N-vanillyl-6-noneamide) is the major constituent of the peppers belonging to the genus Capsicum and responsible for their spicy flavor and burning sensation, also known as pungency. Besides capsaicin, a family of related compounds are present in Capsicum sp. plants, all referred as capsaicinoids. These compounds are capsaicin, dihydrocapsaicin, nordihydrocapsaicin, and homocapsaicin. Capsaicin

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Capsaicin Induces Heme Oxygenase-1 Expression in HepG2 CellsViaActivation of PI3K-Nrf2 Signaling: NAD(P)H:Quinone Oxidoreductase as a Potential Target

Cited by 112 publications

References 32 publications

Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk

Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk

Ethyl Pyruvate Induces Heme Oxygenase-1 Through p38 Mitogen-Activated Protein Kinase Activation by Depletion of Glutathione in RAW 264.7 Cells and Improves Survival in Septic Animals

The Potential Antitumor Effects of Capsaicin

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