Pelargonidin Reduces the TPA Induced Transformation of Mouse Epidermal Cells -potential Involvement of Nrf2 Promoter Demethylation

Overview

Journal Chem Biol Interact

Publisher Elsevier

Specialties Biochemistry
Molecular Biology
Pharmacology

Date 2019 Jun 11

PMID 31181187

Citations 18

Authors

Shanyi Li

Wenji Li

Chao Wang

Renyi Wu

Ran Yin

Hsiao-Chen Kuo

Lujing Wang

Ah-Ng Kong

Affiliations

Soon will be listed here.

Abstract

Pelargonidin, a well-known natural anthocyanidin found in berries strawberries, blueberries, red radishes and other natural foods, has been found to possess health beneficial effects including anti-cancer effect. Herein, we investigated the effect of pelargonidin on cellular transformation in mouse skin epidermal JB6 (JB6 P+) cells induced by tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Pelargonidin treatment significantly decreased colony formation and suppressed cell viability of JB6 P+ cells. Pelargonidin also induced the anti-oxidant response element (ARE)-luciferase activation in HepG2-C8 cells overexpressing the ARE-luciferase reporter. Knockdown of nuclear factor E2-related factor 2 (Nrf2) in shNrf2 JB6 P+ cells enhanced TPA-induced colony formation and attenuated pelargonidin's blocking effect. Pelargonidin reduced the protein levels of genes encoding methyltransferases (DNMTs) and histone deacetylases (HDACs). Importantly, pelargonidin decreased the DNA methylation in the Nrf2 promoter region of JB6 P+ cells and increased Nrf2 downstream target genes expression, such as NAD(P)H/quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), involved in cellular protection. In summary, our results showed that pelargonidin blocks TPA-induced cell transformation. The possible molecular mechanisms of its potential anti-cancer effects against neoplastic transformation may be attributed to its activation of Nrf2-ARE signaling pathway and its cytoprotective effect.

Citing Articles

Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management.

Dewanjee S, Bhattacharya H, Bhattacharyya C, Chakraborty P, Fleishman J, Alexiou A Cell Commun Signal. 2024; 22(1):497.

PMID: 39407193 PMC: 11476647. DOI: 10.1186/s12964-024-01878-2.

Epigenetics of Dietary Phytochemicals in Cancer Prevention: Fact or Fiction.

Chou P, Peter R, Shannar A, Pan Y, Dave P, Xu J Cancer J. 2024; 30(5):320-328.

PMID: 39312452 PMC: 11573353. DOI: 10.1097/PPO.0000000000000742.

Exploring the Therapeutic Potential of Flavonoids in the Management of Cancer.

Singh S, Verma R Curr Pharm Biotechnol. 2024; 26(1):17-47.

PMID: 38591206 DOI: 10.2174/0113892010297456240327062614.

Pelargonidin alleviates acrolein-induced inflammation in human umbilical vein endothelial cells by reducing COX-2 expression through the NF-κB pathway.

Wan Y, Yang H, Zhang G Naunyn Schmiedebergs Arch Pharmacol. 2023; 397(3):1737-1748.

PMID: 37728621 DOI: 10.1007/s00210-023-02712-1.

Dietary Polyphenols Remodel DNA Methylation Patterns of NRF2 in Chronic Disease.

Divyajanani S, Harithpriya K, Ganesan K, Ramkumar K Nutrients. 2023; 15(15).

PMID: 37571283 PMC: 10420661. DOI: 10.3390/nu15153347.

References

Noda Y, Kaneyuki T, Mori A, Packer L . Antioxidant activities of pomegranate fruit extract and its anthocyanidins: delphinidin, cyanidin, and pelargonidin. J Agric Food Chem. 2002; 50(1):166-71. DOI: 10.1021/jf0108765. View

Bird A . DNA methylation patterns and epigenetic memory. Genes Dev. 2002; 16(1):6-21. DOI: 10.1101/gad.947102. View

Ehrlich M . DNA methylation in cancer: too much, but also too little. Oncogene. 2002; 21(35):5400-13. DOI: 10.1038/sj.onc.1205651. View

Zheng W, Wang S . Oxygen radical absorbing capacity of phenolics in blueberries, cranberries, chokeberries, and lingonberries. J Agric Food Chem. 2003; 51(2):502-9. DOI: 10.1021/jf020728u. View

Shaker S, Bernstein M, Momparler L, Momparler R . Preclinical evaluation of antineoplastic activity of inhibitors of DNA methylation (5-aza-2'-deoxycytidine) and histone deacetylation (trichostatin A, depsipeptide) in combination against myeloid leukemic cells. Leuk Res. 2003; 27(5):437-44. DOI: 10.1016/s0145-2126(02)00222-9. View

Esteller M . Relevance of DNA methylation in the management of cancer. Lancet Oncol. 2003; 4(6):351-8. DOI: 10.1016/s1470-2045(03)01115-x. View

Mersch-Sundermann V, Knasmuller S, Wu X, Darroudi F, Kassie F . Use of a human-derived liver cell line for the detection of cytoprotective, antigenotoxic and cogenotoxic agents. Toxicology. 2004; 198(1-3):329-40. DOI: 10.1016/j.tox.2004.02.009. View

Egger G, Liang G, Aparicio A, Jones P . Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004; 429(6990):457-63. DOI: 10.1038/nature02625. View

Iida K, Itoh K, Kumagai Y, Oyasu R, Hattori K, Kawai K . Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis. Cancer Res. 2004; 64(18):6424-31. DOI: 10.1158/0008-5472.CAN-04-1906. View

10.

Zhang Y, Vareed S, Nair M . Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables. Life Sci. 2005; 76(13):1465-72. DOI: 10.1016/j.lfs.2004.08.025. View

11.

Waris G, Ahsan H . Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog. 2006; 5:14. PMC: 1479806. DOI: 10.1186/1477-3163-5-14. View

12.

Halliwell B . Oxidative stress and cancer: have we moved forward?. Biochem J. 2006; 401(1):1-11. DOI: 10.1042/BJ20061131. View

13.

Ou J, Torrisani J, Unterberger A, Provencal N, Shikimi K, Karimi M . Histone deacetylase inhibitor Trichostatin A induces global and gene-specific DNA demethylation in human cancer cell lines. Biochem Pharmacol. 2007; 73(9):1297-307. DOI: 10.1016/j.bcp.2006.12.032. View

14.

Seifried H, Anderson D, Fisher E, Milner J . A review of the interaction among dietary antioxidants and reactive oxygen species. J Nutr Biochem. 2007; 18(9):567-79. DOI: 10.1016/j.jnutbio.2006.10.007. View

15.

Bostick M, Kim J, Esteve P, Clark A, Pradhan S, Jacobsen S . UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science. 2007; 317(5845):1760-4. DOI: 10.1126/science.1147939. View

16.

Bralley E, Greenspan P, Hargrove J, Wicker L, Hartle D . Topical anti-inflammatory activity of Polygonum cuspidatum extract in the TPA model of mouse ear inflammation. J Inflamm (Lond). 2008; 5:1. PMC: 2267461. DOI: 10.1186/1476-9255-5-1. View

17.

Wang R, An J, Ji F, Jiao H, Sun H, Zhou D . Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues. Biochem Biophys Res Commun. 2008; 373(1):151-4. DOI: 10.1016/j.bbrc.2008.06.004. View

18.

Wang L, Stoner G . Anthocyanins and their role in cancer prevention. Cancer Lett. 2008; 269(2):281-90. PMC: 2582525. DOI: 10.1016/j.canlet.2008.05.020. View

19.

Nguyen T, Nioi P, Pickett C . The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009; 284(20):13291-5. PMC: 2679427. DOI: 10.1074/jbc.R900010200. View

20.

Yu S, Khor T, Cheung K, Li W, Wu T, Huang Y . Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice. PLoS One. 2010; 5(1):e8579. PMC: 2799519. DOI: 10.1371/journal.pone.0008579. View