Anti-Inflammatory Effect of Protopine through MAPK and NF-κB Signaling Regulation in HepG2 Cell
Abstract
:1. Introduction
2. Results
2.1. Effect of Protopine on the HepG2 Cell Viability
2.2. Inhibitory Effect of Protopine on the PMA-Induced Inflammatory Transcription Factor NF-κB Signals in HepG2 Cells
2.3. Effect of Protopine on the Inhibition of PMA-Induced Expression of COX-2 and MMP-9 in HepG2 Cells
2.4. Effect of Protopine on the PMA-Induced Inflammatory Signaling Pathway MAPK in HepG2 Cells
3. Discussion
4. Materials and Methods
4.1. Material
4.2. Cell Culture and Viability Measurement
4.3. Western Blot Analysis
4.4. Quantitative Polymerase Chain Reaction
4.5. Immunofluorescence
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Wada, Y.; Kaga, H.; Uchiito, S.; Kumazawa, E.; Tomiki, M.; Onozaki, Y.; Kurono, N.; Tokuda, M.; Ohkuma, T.; Orito, K. On the synthesis of protopine alkaloids. J. Org. Chem. 2007, 72, 7301–7306. [Google Scholar] [CrossRef] [PubMed]
- Alam, M.B.; Ju, M.-K.; Kwon, Y.-G.; Lee, S.H. Protopine attenuates inflammation stimulated by carrageenan and LPS via the MAPK/NF-κB pathway. Food Chem. Toxicol. 2019, 131, 110583. [Google Scholar] [CrossRef] [PubMed]
- He, K.; Gao, J.-L. Protopine inhibits heterotypic celladhesion in MDA-MB-231 cells through down-regulation of multi-adhesive factors. Afr. J. Tradit. Complementary Altern. Med. 2014, 11, 415–424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bae, D.-S.; Kim, Y.-H.; Pan, C.-H.; Nho, C.-W.; Samdan, J.; Yansan, J.; Lee, J.-K. Protopine reduces the inflammatory activity of lipopolysaccharide-stimulated murine macrophages. BMB Rep. 2012, 45, 108–113. [Google Scholar] [CrossRef] [Green Version]
- Garcia-Gil, M.; Turri, B.; Gabriele, M.; Pucci, L.; Agnarelli, A.; Lai, M.; Freer, G.; Pistello, M.; Vignali, R.; Batistoni, R. Protopine/gemcitabine combination induces cytotoxic or cytoprotective effects in cell type-specific and dose-dependent manner on human cancer and normal cells. Pharmaceuticals 2021, 14, 90. [Google Scholar] [CrossRef]
- Son, Y.; An, Y.; Jung, J.; Shin, S.; Park, I.; Gwak, J.; Ju, B.G.; Chung, Y.H.; Na, M.; Oh, S. Protopine isolated from Nandina domestica induces apoptosis and autophagy in colon cancer cells by stabilizing p53. Phytother. Res. 2019, 33, 1689–1696. [Google Scholar] [CrossRef]
- Rathi, A.; Srivastava, A.K.; Shirwaikar, A.; Rawat, A.K.S.; Mehrotra, S. Hepatoprotective potential of Fumaria indica Pugsley whole plant extracts, fractions and an isolated alkaloid protopine. Phytomedicine 2008, 15, 470–477. [Google Scholar] [CrossRef]
- Obata, T.; Brown, G.E.; Yaffe, M.B. MAP kinase pathways activated by stress: The p38 MAPK pathway. Crit. Care Med. 2000, 28, N67–N77. [Google Scholar] [CrossRef]
- Lee, W.-J.; Wu, L.-F.; Chen, W.-K.; Wang, C.-J.; Tseng, T.-H. Inhibitory effect of luteolin on hepatocyte growth factor/scatter factor-induced HepG2 cell invasion involving both MAPK/ERKs and PI3K–Akt pathways. Chem.-Biol. Interact. 2006, 160, 123–133. [Google Scholar] [CrossRef]
- Panahi, G.; Pasalar, P.; Zare, M.; Rizzuto, R.; Meshkani, R. High glucose induces inflammatory responses in HepG2 cells via the oxidative stress-mediated activation of NF-κB, and MAPK pathways in HepG2 cells. Arch. Physiol. Biochem. 2018, 124, 468–474. [Google Scholar] [CrossRef]
- Weng, C.-J.; Chau, C.-F.; Hsieh, Y.-S.; Yang, S.-F.; Yen, G.-C. Lucidenic acid inhibits PMA-induced invasion of human hepatoma cells through inactivating MAPK/ERK signal transduction pathway and reducing binding activities of NF-κB and AP-1. Carcinogenesis 2008, 29, 147–156. [Google Scholar] [CrossRef]
- Keshari, R.S.; Verma, A.; Barthwal, M.K.; Dikshit, M. Reactive oxygen species-induced activation of ERK and p38 MAPK mediates PMA-induced NETs release from human neutrophils. J. Cell. Biochem. 2013, 114, 532–540. [Google Scholar] [CrossRef] [PubMed]
- Kim, S.O.; Chun, K.S.; Kundu, J.K.; Surh, Y.J. Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-κB and p38 MAPK in mouse skin. Biofactors 2004, 21, 27–31. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Yuan, L.; Xiao, H.; Xiao, C.; Wang, Y.; Liu, X. Momordin Ic induces HepG2 cell apoptosis through MAPK and PI3K/Akt-mediated mitochondrial pathways. Apoptosis 2013, 18, 751–765. [Google Scholar] [CrossRef] [PubMed]
- Huang, J.; Wu, L.; Tashiro, S.-i.; Onodera, S.; Ikejima, T. Reactive oxygen species mediate oridonin-induced HepG2 apoptosis through p53, MAPK, and mitochondrial signaling pathways. J. Pharmacol. Sci. 2008, 107, 370–379. [Google Scholar] [CrossRef] [Green Version]
- Arts, J.; Grimbergen, J.; Bosma, P.J.; Rahmsdorf, H.J.; Kooistra, T. Role of C-Jun and Proximal Phorbol 12-Myristate-13-Acetate-(PMA)-Responsive Elements in the Regulation of Basal and PMA-Stimulated Plasminogen-Activator Inhibitor-1 Gene Expression in HepG2. Eur. J. Biochem. 1996, 241, 393–402. [Google Scholar] [CrossRef]
- Wang, D.; Stroup, D.; Marrapodi, M.; Crestani, M.; Galli, G.; Chiang, J. Transcriptional regulation of the human cholesterol 7 alpha-hydroxylase gene (CYP7A) in HepG2 cells. J. Lipid Res. 1996, 37, 1831–1841. [Google Scholar] [CrossRef]
- Kubitz, R.; Huth, C.; Schmitt, M.; Horbach, A.; Kullak-Ublick, G.; Häussinger, D. Protein kinase C–dependent distribution of the multidrug resistance protein 2 from the canalicular to the basolateral membrane in human HepG2 cells. Hepatology 2001, 34, 340–350. [Google Scholar] [CrossRef]
- Kim, J.-B.; Han, A.-R.; Park, E.-Y.; Kim, J.-Y.; Cho, W.; Lee, J.; Seo, E.-K.; Lee, K.-T. Inhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin through the NF-κB inactivation in RAW 264.7 macrophage cells. Biol. Pharm. Bull. 2007, 30, 2345–2351. [Google Scholar] [CrossRef] [Green Version]
- Hseu, Y.-C.; Wu, F.-Y.; Wu, J.-J.; Chen, J.-Y.; Chang, W.-H.; Lu, F.-J.; Lai, Y.-C.; Yang, H.-L. Anti-inflammatory potential of Antrodia camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-κB pathway. Int. Immunopharmacol. 2005, 5, 1914–1925. [Google Scholar] [CrossRef]
- Kiemer, A.K.; Hartung, T.; Huber, C.; Vollmar, A.M. Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-κB pathway. J. Hepatol. 2003, 38, 289–297. [Google Scholar] [CrossRef]
- Bagherieh, M.; Kheirollahi, A.; Zamani-Garmsiri, F.; Emamgholipour, S.; Meshkani, R. Folic acid ameliorates palmitate-induced inflammation through decreasing homocysteine and inhibiting NF-κB pathway in HepG2 cells. Arch. Physiol. Biochem. 2021, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Yu, M.H.; Gwon Im, H.; Gyu Lee, S.; Kim, D.-I.; Jeong Seo, H.; Lee, I.-S. Inhibitory effect of immature plum on PMA-induced MMP-9 expression in human hepatocellular carcinoma. Nat. Prod. Res. 2009, 23, 704–718. [Google Scholar] [CrossRef] [PubMed]
- Arts, J.; Grimbergen, J.; Toet, K.; Kooistra, T. On the role of c-Jun in the induction of PAI-1 gene expression by phorbol ester, serum, and IL-1α in HepG2 cells. Arterioscler. Thromb. Vasc. Biol. 1999, 19, 39–46. [Google Scholar] [CrossRef] [Green Version]
- Dai, W.; Wang, F.; He, L.; Lin, C.; Wu, S.; Chen, P.; Zhang, Y.; Shen, M.; Wu, D.; Wang, C. Genistein inhibits hepatocellular carcinoma cell migration by reversing the epithelial–mesenchymal transition: Partial mediation by the transcription factor NFAT1. Mol. Carcinog. 2015, 54, 301–311. [Google Scholar] [CrossRef]
- Yu, M.-H.; Lee, S.-O. Hydroquinone stimulates cell invasion through activator protein-1-dependent induction of MMP-9 in HepG2 human hepatoma cells. Food Chem. Toxicol. 2016, 89, 120–125. [Google Scholar] [CrossRef]
- Weng, C.-J.; Wu, C.-F.; Huang, H.-W.; Wu, C.-H.; Ho, C.-T.; Yen, G.-C. Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells. J. Agric. Food Chem. 2010, 58, 2886–2894. [Google Scholar] [CrossRef]
- Roomi, M.; Monterrey, J.; Kalinovsky, T.; Rath, M.; Niedzwiecki, A. Patterns of MMP-2 and MMP-9 expression in human cancer cell lines. Oncol. Rep. 2009, 21, 1323–1333. [Google Scholar]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kim, M.; Kim, H.; Kim, H. Anti-Inflammatory Effect of Protopine through MAPK and NF-κB Signaling Regulation in HepG2 Cell. Molecules 2022, 27, 4601. https://doi.org/10.3390/molecules27144601
Kim M, Kim H, Kim H. Anti-Inflammatory Effect of Protopine through MAPK and NF-κB Signaling Regulation in HepG2 Cell. Molecules. 2022; 27(14):4601. https://doi.org/10.3390/molecules27144601
Chicago/Turabian StyleKim, MinGyu, Hyuck Kim, and Hojun Kim. 2022. "Anti-Inflammatory Effect of Protopine through MAPK and NF-κB Signaling Regulation in HepG2 Cell" Molecules 27, no. 14: 4601. https://doi.org/10.3390/molecules27144601