Effects of Chrysin on Oral Squamous Cell Carcinoma In Vitro

Abstract

Objective Chrysin is a hydroxylated flavonoid derived from “propolis or bee glue,” a natural product. Previous research on chrysin's biological functions, including anticancer activity, had been reported. However, chrysin's effect on oral squamous cell carcinoma (OSCC) is still scarce. This article aimed to test the cytotoxicity, antiproliferative, antimigration, anti-invasion, and apoptotic effects of purified chrysin in two OSCC cell lines, HSC4 and SCC25.

Materials and Methods The malignant phenotype was assessed using cell proliferation, wound healing, and transwell assays. Cell apoptosis was determined using flow cytometry. The positive control was OSCC cells treated with cisplatin, and the negative control was OSCC cells incubated with 0.1% dimethyl sulfoxide.

Results Chrysin at concentrations of 100 and 200 µM could inhibit OSCC cell proliferation, migration, and invasion, as well as enhance cell apoptosis, particularly in the early stages of apoptosis.

Conclusion In OSCC cell lines, chrysin has been demonstrated to be an effective antioncogenic agent. Additional research is required to confirm the results. Chrysin should be suggested as a possible alternative therapeutic application for OSCC.

Keywords

chrysin - oral squamous cell carcinoma - proliferation - migration - invasion - apoptosis

Publikationsverlauf

Artikel online veröffentlicht:
27. September 2022

• References

• 1 Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 2020; 6 (01) 92
• 2 Sung H, Ferlay J, Siegel RL. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (03) 209-249
• 3 Ringash J, Bernstein LJ, Devins G. et al. Head and neck cancer survivorship: learning the needs, meeting the needs. Semin Radiat Oncol 2018; 28 (01) 64-74
• 4 Talebi M, Talebi M, Farkhondeh T. et al. An updated review on the versatile role of chrysin in neurological diseases: chemistry, pharmacology, and drug delivery approaches. Biomed Pharmacother 2021; 141: 111906
• 5 Siess M-H, Le Bon A-M, Canivenc-Lavier M-C. et al. Flavonoids of honey and propolis:  characterization and effects on hepatic drug-metabolizing enzymes and benzo[a]pyrene − DNA binding in rats. J Agri Food Chem 1996; 44 (08) 2297-2301
• 6 Khoo BY, Chua SL, Balaram P. Apoptotic effects of chrysin in human cancer cell lines. Int J Mol Sci 2010; 11 (05) 2188-2199
• 7 Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Scientific World Journal 2013;2013:162750
• 8 Celińska-Janowicz K, Zaręba I, Lazarek U. et al. Constituents of propolis: chrysin, caffeic acid, p-coumaric acid, and ferulic acid induce PRODH/POX-dependent apoptosis in human tongue squamous cell carcinoma cell (CAL-27). Front Pharmacol 2018; 9: 336
• 9 Jiang L, Ji N, Zhou Y. et al. CAL 27 is an oral adenosquamous carcinoma cell line. Oral Oncol 2009; 45 (11) e204-e207
• 10 Thanakappan P, Venkata NS, Amudala R, Botu M. Adenosquamous carcinoma of oral cavity. J Cancer Res Ther 2015; 11 (04) 1034
• 11 Vajrabhaya LO, Korsuwannawong S, Surarit R. Cytotoxic and the proliferative effect of cuttlefish bone on MC3T3-E1 osteoblast cell line. Eur J Dent 2017; 11 (04) 503-507
• 12 Colombo M, Ceci M, Felisa E, Poggio C, Pietrocola G. Cytotoxicity evaluation of a new ozonized olive oil. Eur J Dent 2018; 12 (04) 585-589
• 13 Rujirachotiwat A, Suttamanatwong S. Curcumin promotes collagen type I, keratinocyte growth factor-1, and epidermal growth factor receptor expressions in the in vitro wound healing model of human gingival fibroblasts. Eur J Dent 2021; 15 (01) 63-70
• 14 Amir LR, Soeroso Y, Fatma D. et al. Periodontal ligament cell sheets and RGD-modified chitosan improved regeneration in the horizontal periodontal defect model. Eur J Dent 2020; 14 (02) 306-314
• 15 Momose F, Araida T, Negishi A, Ichijo H, Shioda S, Sasaki S. Variant sublines with different metastatic potentials selected in nude mice from human oral squamous cell carcinomas. J Oral Pathol Med 1989; 18 (07) 391-395
• 16 Bair EL, Massey CP, Tran NL. et al. Integrin- and cadherin-mediated induction of the matrix metalloprotease matrilysin in cocultures of malignant oral squamous cell carcinoma cells and dermal fibroblasts. Exp Cell Res 2001; 270 (02) 259-267
• 17 Moghadam ER, Ang HL, Asnaf SE. et al. Broad-spectrum preclinical antitumor activity of chrysin: current trends and future perspectives. Biomolecules 2020; 10 (10) E1374
• 18 Friedl P, Gilmour D. Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol 2009; 10 (07) 445-457
• 19 Bravo-Cordero JJ, Hodgson L, Condeelis J. Directed cell invasion and migration during metastasis. Curr Opin Cell Biol 2012; 24 (02) 277-283
• 20 Samarghandian S, Nezhad MA, Mohammadi G. Role of caspases, Bax and Bcl-2 in chrysin-induced apoptosis in the A549 human lung adenocarcinoma epithelial cells. Anticancer Agents Med Chem 2014; 14 (06) 901-909
• 21 Dong W, Chen A, Chao X. et al. Chrysin inhibits proinflammatory factor-induced EMT phenotype and cancer stem cell-like features in HeLa cells by blocking the NF-κB/twist axis. Cell Physiol Biochem 2019; 52 (05) 1236-1250
• 22 Ryu S, Lim W, Bazer FW, Song G. Chrysin induces death of prostate cancer cells by inducing ROS and ER stress. J Cell Physiol 2017; 232 (12) 3786-3797
• 23 Xu Y, Tong Y, Ying J. et al. Chrysin induces cell growth arrest, apoptosis, and ER stress and inhibits the activation of STAT3 through the generation of ROS in bladder cancer cells. Oncol Lett 2018; 15 (06) 9117-9125
• 24 Zhong X, Liu D, Jiang Z. et al. Chrysin induced cell apoptosis and inhibited invasion through regulation of TET1 expression in gastric cancer cells. OncoTargets Ther 2020; 13: 3277-3287
• 25 Raina R, Afroze N, Kedhari Sundaram M. et al. Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways. Eur Rev Med Pharmacol Sci 2021; 25 (05) 2206-2220
• 26 Samarghandian S, Afshari JT, Davoodi S. Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line pc-3. Clinics (São Paulo) 2011; 66 (06) 1073-1079
• 27 Bin-Alee F, Arayataweegool A, Buranapraditkun S. et al. Evaluation of lymphocyte apoptosis in patients with oral cancer. J Appl Oral Sci 2020; 28: e20200124
• 28 Voss AK, Strasser A. The essentials of developmental apoptosis. F1000Res. 2020 ;9.