REVIEW PAPER
 
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
Known for their strong antioxidant properties, flavonoids are the major polyphenolic compounds found in a wide variety of plants, vegetables, and fruits. A growing number of reports has indicated their anticancer effect. Affecting numerous cellular pathways, polyphenols suppress carcinogenesis which allows for new strategies developed to fight skin cancer. Given the high morbidity and mortality rates due to skin cancer, the aim of the review is to summarize earlier studies on the role of flavonoids in skin cancer prevention and treatment.

Review methods:
A search was conducted using the PubMed databases. Using keywords related to flavonoids and skin cancer, articles in Polish and English were manually searched. Duplicate papers were removed, and the bibliographies of selected studies as well as bibliographies from other reviews were reviewed in order to incorporate additional relevant studies into the review.

Brief description of the state of knowledge:
Flavonoids are effective immunomodulators since they modulate cell growth, induce apoptosis, and reduce reactive oxygen species production. They have DNA repair abilities that can be used to prevent various skin diseases caused by excessive sun exposure. They can prevent, postpone, or completely stop photocarcinogenesis.

Summary:
Because of their effect on numerous cellular pathways, flavonoids have been studied extensively to confirm their preventive and therapeutic potential in skin cancer. Flavonoids have been shown in studies to shrink cancerous tumours and prevent metastasis. Their use in prevention and anticancer therapies may contribute to lower skin cancer mortality rates.

 
REFERENCES (40)
1.
Juszczak AM, Wöelfle U, Končić MZ, Tomczyk M. Skin cancer, including related pathways and therapy and the role of luteolin derivatives as potential therapeutics. Med Res Rev. 2022;42(4):1423–1462. https://doi.org/10.1002/med.21....
 
2.
Imran M, Rauf A, Abu-Izneid T, Nadeem M, Shariati MA, Khan IA, Imran A, Orhan IE, Rizwan M, Atif M, Gondal TA, Mubarak MS. Luteolin, a flavonoid, as an anticancer agent: A review. Biomed Pharmacother. 2019;112:108612. https://doi.org/10.1016/j.biop....
 
3.
Islam SU, Ahmed MB, Ahsan H, Islam M, Shehzad A, Sonn JK, Lee YS. An Update on the Role of Dietary Phytochemicals in Human Skin Cancer: New Insights into Molecular Mechanisms. Antioxidants (Basel). 2020;9(10):916. https://doi.org/10.3390/antiox....
 
4.
Iqbal J, Abbasi BA, Ahmad R, Batool R, Mahmood T, Ali B, Khalil AT, Kanwal S, Afzal Shah S, Alam MM, Bashir S, Badshah H, Munir A. Potential phytochemicals in the fight against skin cancer: Current landscape and future perspectives. Biomed Pharmacother. 2019;109:1381–1393. https://doi.org/10.1016/j.biop....
 
5.
Afaq F, Katiyar SK. Polyphenols: skin photoprotection and inhibition of photocarcinogenesis. Mini Rev Med Chem. 2011;11(14):1200–1215. https://doi.org/10.2174/138955....
 
6.
Penta D, Somashekar BS, Meeran SM. Epigenetics of skin cancer: Interventions by selected bioactive phytochemicals. Photodermatol Photoimmunol Photomed. 2018;34(1):42–49. https://doi.org/10.1111/phpp.1....
 
7.
Aboul-Fettouh N, Morse D, Patel J, Migden MR. Immunotherapy and Systemic Treatment of Cutaneous Squamous Cell Carcinoma. Dermatol Pract Concept. 2021;11(S2):e2021169S. https://doi.org/10.5826/dpc.11....
 
8.
Kim HS, Kacew S, Lee BM. Genetic and epigenetic cancer chemo-prevention on molecular targets during multistage carcinogenesis. Arch Toxicol. 2016;90(10):2389–404. https://doi.org/10.1007/s00204....
 
9.
PDQ® Adult Treatment Editorial Board. PDQ Skin Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated 2022.02.11. Available at: https://www.cancer.gov/types/s.... (accessed: 2022.06.01).
 
10.
Sajadimajd S, Bahramsoltani R, Iranpanah A, Kumar Patra J, Das G, Gouda S, Rahimi R, Rezaeiamiri E, Cao H, Giampieri F, Battino M, Tundis R, Campos MG, Farzaei MH, Xiao J. Advances on Natural Polyphenols as Anticancer Agents for Skin Cancer. Pharmacol Res. 2020;151:104584. https://doi.org/10.1016/j.phrs....
 
11.
Magcwebeba TU, Swart P, Swanevelder S, Joubert E, Gelderblom WC. In Vitro Chemopreventive Properties of Green Tea, Rooibos and Honeybush Extracts in Skin Cells. Molecules. 2016;21(12):1622. https://doi.org/10.3390/molecu....
 
12.
Conney AH, Kramata P, Lou YR, Lu YP. Effect of caffeine on UVB-induced carcinogenesis, apoptosis, and the elimination of UVB-induced patches of p53 mutant epidermal cells in SKH-1 mice. Photochem Photobiol. 2008;84(2):330–8. https://doi.org/10.1111/j.1751....
 
13.
Meeran SM, Mantena SK, Elmets CA, Katiyar SK. Rtraction: (-)-Epigallocatechin-3-Gallate Prevents Photocarcinogenesis in Mice through Interleukin-12-Dependent DNA Repair. Cancer Res. 2018;78(23):6709. https://doi.org/10.1158/0008-5....
 
14.
Afaq F, Ahmad N, Mukhtar H. Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice. Oncogene. 2003;22:9254–64. https://doi.org/10.1038/sj.onc....
 
15.
Vayalil PK, Elmets CA, Katiyar SK. Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin. Retraction. Carcinogenesis. 2018;39(5):738. https://doi.org/10.1093/carcin....
 
16.
Mantena SK, Roy AM, Katiyar SK. Epigallocatechin-3-Gallate Inhibits Photocarcinogenesis Through Inhibition of Angiogenic Factors and Activation of CD8+ T Cells in Tumors. Photochem Photobiol. 2018;94(3):618. https://doi.org/10.1111/php.12....
 
17.
Ellis LZ, Liu W, Luo Y, Okamoto M, Qu D, Dunn JH, Fujita M. Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1beta secretion. Biochem Biophys Res Commun. 2011;414(3):551–556. https://doi.org/10.1016/j.bbrc....
 
18.
Singh T, Katiyar SK. Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by Targeting COX-2, PGE2 Receptors and Epithelial-to-Mesenchymal Transition. PLoS One. 2018;13(12):e0210345. https://doi.org/10.1371/journa....
 
19.
Montes de Oca MK, Pearlman RL, McClees SF, Strickland R, Afaq F. Phytochemicals for the Prevention of Photocarcinogenesis. Photochem Photobiol. 2017;93(4):956–974. https://doi.org/10.1111/php.12....
 
20.
Afaq F, Malik A, Syed D, Maes D, Matsui MS, Mukhtar H. Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes. Photochem Photobiol. 2005;81:38–45. https://doi.org/10.1562/2004-0....
 
21.
Marcílio Cândido T, Bueno Ariede M, Vieira Lima F, de Souza Guedes L, Robles Velasco MV, Rolim Baby A, Rosado C. Dietary Supplements and the Skin: Focus on Photoprotection and Antioxidant Activity-A Review. Nutrients. 2022;14(6):1248. https://doi.org/10.3390/nu1406....
 
22.
Liu C, Guo H, DaSilva NA, Li D, Zhang K, Wan Y, Gao XH, Chen HD, Seeram NP, Ma H. Pomegranate (Punica granatum) Phenolics Ameliorate Hydrogen Peroxide-Induced Oxidative Stress and Cytotoxicity in Human Keratinocytes. J Funct Foods. 2019;54:559–567. https://doi.org/10.1016/j.jff.....
 
23.
Koltai T, Fliegel L. Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions. J Evid Based Integr Med. 2022;27:2515690X211068826. https://doi.org/10.1177/251569....
 
24.
Mallikarjuna G, Dhanalakshmi S, Singh RP, Agarwal C, Agarwal R. Silibinin protects against photocarcinogenesis via modulation of cell cycle regulators, mitogen-activated protein kinases, and Akt signaling. Cancer Res. 2004;64:6349–56. https://doi.org/10.1158/0008-5....
 
25.
Ng CY, Yen H, Hsiao HY, Su SC. Phytochemicals in Skin Cancer Prevention and Treatment: An Updated Review. Int J Mol Sci. 2018;19(4):941. https://doi.org/10.3390/ijms19....
 
26.
Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA, Ahmad B, Atif M, Mubarak MS, Sytar O, Zhilina OM, Garsiya ER, Smeriglio A, Trombetta D, Pons DG, Martorell M, Cardoso SM, Razis AFA, Sunusi U, Kamal RM, Rotariu LS, Butnariu M, Docea AO, Calina D. Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits. Oxid Med Cell Longev. 2021;2021:3268136. https://doi.org/10.1155/2021/3....
 
27.
Yang Y, Wang H, Wang J, Li X, Ma M, Yang W. Effect of livin gene suppression by genistein on apoptosis, cell cycle and proliferation of malignant melanoma LiBr cells. Nan Fang Yi Ke Da Xue Xue Bao. 2012;32(8):1163–1167. https://pubmed.ncbi.nlm.nih.go....
 
28.
Pal HC, Hunt KM, Diamond A, Elmets CA, Afaq F. Phytochemicals for the Management of Melanoma. Mini Rev Med Chem. 2017;17(15):1500. https://doi.org/10.2174/138955....
 
29.
Pal HC, Sharma S, Strickland LR, Katiyar SK, Ballestas ME, Athar M, Elmets CA, Afaq F. Fisetin inhibits human melanoma cell invasion through promotion of mesenchymal to epithelial transition and by targeting MAPK and NFkappaB signaling pathways. PLoS One. 2014;9(1):e86338. https://doi.org/10.1371/journa....
 
30.
Yaghoubi F, Motlagh NSH, Naghib SM, Haghiralsadat F, Jaliani HZ, Moradi A. A functionalized graphene oxide with improved cytocompatibility for stimuli-responsive co-delivery of curcumin and doxorubicin in cancer treatment. Sci Rep. 2022;12(1):1959. https://doi.org/10.1038/s41598....
 
31.
Nocito MC, De Luca A, Prestia F, Avena P, La Padula D, Zavaglia L, Sirianni R, Casaburi I, Puoci F, Chimento A, Pezzi V. Antitumoral Activities of Curcumin and Recent Advances to ImProve Its Oral Bioavailability. Biomedicines. 2021;9(10):1476. https://doi.org/10.3390/biomed....
 
32.
Vallée A, Lecarpentier Y, Vallée JN. Curcumin: a therapeutic strategy in cancers by inhibiting the canonical WNT/ß-catenin pathway. J Exp Clin Cancer Res. 2019;38(1):323. https://doi.org/10.1186/s13046....
 
33.
Ghi?u A, Schwiebs A, Radeke HH, Avram S, Zupko I, Bor A, Pavel IZ, Dehelean CA, Oprean C, Bojin F, Farcas C, Soica C, Duicu O, Danciu C. A Comprehensive Assessment of Apigenin as an Antiproliferative, Proapoptotic, Antiangiogenic and Immunomodulatory Phyto com-pound. Nutrients. 2019;11(4):858. https://doi.org/10.3390/nu1104....
 
34.
Das S, Das J, Samadder A, Boujedaini N, Khuda-Bukhsh AR. Apigenin-induced apoptosis in A375 and A549 cells through selective action and dysfunction of mitochondria.Exp Biol Med (Maywood). 2012;237(12):1433–1448. https://doi.org/10.1258/ebm.20....
 
35.
Ahmed S, Khan H, Fratantonio D, Hasan MM, Sharifi S, Fathi N, Ullah H, Rastrelli L. Apoptosis induced by luteolin in breast cancer: Mechanistic and therapeutic perspectives. Phytomedicine. 2019;59:152883. https://doi.org10.1016/j.phyme....
 
36.
Ruan JS, Liu YP, Zhang L, Yan LG, Fan FT, Shen CS, Wang AY, Zheng SZ, Wang SM, Lu Y. Luteolin reduces the invasive potential of malignant melanoma cells by targeting beta3 integrin and the epithelial-mesenchymal transition. Acta Pharmacol Sin. 2012;33(10):1325–1331. https://doi.org/10.1038/aps.20....
 
37.
Yao X, Jiang W, Yu D, Yan Z. Luteolin Inhibits Proliferation and Induces Apoptosis of Human Melanoma Cells: InVivo and in Vitro by Suppressing MMP-2 and MMP-9 through the PI3K/AKT Pathway. Food Funct. 2019;10:703–712. https://doi.org/10.1039/c8fo02....
 
38.
Kim SH, Yoo ES, Woo JS, Han SH, Lee JH, Jung SH, Kim HJ, Jung JY. Antitumor and Apoptotic Effects of Quercetin on Human Melanoma Cells Involving JNK/P38 MAPK Signaling Activation. Eur J Pharmacol. 2019;860:172568. https://doi.org/10.1016/j.ejph....
 
39.
Michaud-Levesque J, Bousquet-Gagnon N, Béliveau R. Quercetin abrogates IL-6/STAT3 signaling and inhibits glioblastoma cell line growth and migration. Exp Cell Res. 2012;318(8):925–35. https://doi.org/10.1016/j.yexc....
 
40.
Momtaz S, Niaz K, Maqbool F, Abdollahi M, Rastrelli L, Nabavi SM. STAT3 targeting by polyphenols: Novel therapeutic strategy for melanoma. Biofactors. 2017;43(3):347–70. https://doi.org/10.1002/biof.1....
 
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