Chrysin and its potential antineoplastic effect

  • Patrycja Chylińska-Wrzos Chair and Department of Histology and Embryology with Experimental Cytology Unit, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
  • Marta Lis-Sochocka Chair and Department of Histology and Embryology with Experimental Cytology Unit, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
  • Barbara Jodłowska-Jędrych Chair and Department of Histology and Embryology with Experimental Cytology Unit, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
Keywords: Chrysin, Flavonoids, Propolis, Anticancer activity


In 2012, in Europe, there were noticed over 3 million new cases of cancer and 1.75 million of deaths from cancer. Numerous anticancer agents are cytotoxic, can damage normal cells, and they can cause serious side effects. Currently, natural and non-toxic agents are being sought that reduce the cost of therapy, are more effective and targeted, and do not damage healthy cells. Chrysin which belong to flavonoids family as natural substance, has multiple anticancer activities. It has been reported that chrysin can induce apoptosis in tumour cells by different mechanism. In our work we demonstrated the potential use of chrysin in gastrointestinal, breast, cervical, and lung cancer. In conclusion it is proven that chrysin or combination of chrysin with other related drugs can effectively improve the effectiveness of anticancer therapy. Furthermore, new agents, such as nanoparticles, may show greater efficacy, and better targeting, hence, less side effects on healthy cells. Based on these results, nanochrysin it offers as new and effective drug delivery system. Moreover, it has been reported that chrysin is a potential antitumor but also an adjuvant agent that can be used in combination with other antimetastatic substances to reduce tumor metastasis.



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1. Bankova V. Chemical diversity of propolis and the problem of standardization. J Ethnopharmacol. 2005; 100: 114-117.
2. Kurek-Górecka A, Rzepecka-Stojko A, Górecki M, Stojko J, Sosada M, Swierczek-Zieba G. Structure and antioxidant activity of polyphenols derived from propolis. Molecules. 2014; 19(1): 78-101.
3. Lotfy M. Biological activity of bee propolis in health and disease. Asian Pac J Cancer Prev. 2006; 7: 22-31.
4. Bankova V, Popova M, Trusheva B. Propolis volatile compounds: chemical diversity and biological activity: a review. Chem Central J. 2014; 8: 28.
5. Bankova V, PopovaM, Trusheva B. New emerging fields of application of propolis. Maced J Chem Chem Engin. 2016; 35(1): 1-11.
6. De Castro SL. Propolis: biological and pharmacological activities. Therapeutic uses of this bee-product. Annu Rev Biomed Sci. 2001; 3: 49-83.
7. Miguel MG, Antunes MD. Is propolis safe as an alternative medicine? J Pharm BioAllied Sci. 2011; 3(4): 479-495.
8. Sabir A. The Effect of Propolis on Cytokines during Dental Pulp Inflammation. Journal of Apiculture. 2016; 31(1): 135-142.
9. Sforcin JM. Biological properties and therapeutic applications of propolis. Phytother Res. 2016; 30(6): 894-905.
10. Huang S, Zhang CP, Wang K, Li GQ, Hu FL. Recent advances in the chemical composition of propolis. Molecules. 2014; 19(12): 19610-19632.
11. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Scient World J. 2013: 162750.
12. Nabavi SF, Braidy N, Habtemariam S, Orhan IE, Daglia M, Manayi A, et al. Neuroprotective effects of chrysin: from chemistry to medicine. Neurochem Int. 2015; 90: 224-231.
13. Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev. 2014; 8(16): 122-146.
14. Brodowska KM. Natural flavonoids: classification, potential role, and application of flavonoid analogues. Eur J Biol Res. 2017; 7(2): 108-123.
15. Majewski G, Lubecka-Pietruszewska K, Kaufman-Szymczyk A, Fabianowska-Majewska K. Anticancer properties of selected plant polyphenols from the group of flavonoids and stilbenes. Zdr Publ. 2012; 122(4): 434-439.
16. Marais JPJ, Deavours B, Dixon RA, Ferreira D. The stereochemistry of flavonoids. In: The science of flavonoids. Ohio, Springer, 2006: 1-4.
17. Rzepecka-Stojko A, Stojko J, Kurek-Górecka A, Górecki M, Kabała-Dzik A, Kubina R, et al. Polyphenols from bee pollen: structure, absorption, metabolism and biological activity. Molecules. 2015; 20(12): 21732-21749.
18. Kedika B, Thotla K, Noole V, Chepyala KR. Research progress of chrysin derivatives with potential biological activities. J Chem Pharm Res. 2016; 8(8): 1210-1222.
19. Basu A, Das AS, Majumder M, Mukhopadhyay R. Antiatherogenic roles of dietary flavonoids chrysin, quercetin, and luteolin. J Cardiovasc Pharmacol. 2016; 68(1): 89-96.
20. Kaidama WM, Gacche RN. Anti-inflammatory activity of chrysin in acute and chronic phases of inflammation in Guinea Pigs. Int J Scient Res Publ. 2015; 5(2): 427-431.
21. Song X, Liu Y, Ma J, He J, Zhenget X, Lei X, et al. Synthesis of novel amino acid derivatives containing chrysin as anti-tumor agents against human gastric carcinoma MGC-803 cells. Med Chem Res. 2015; 24: 1789-1798.
22. Tsuji PA, Winn RN, Walle T. Accumulation and metabolism of the anticancer flavonoid 5,7-dimethoxyflavone compared to its unmethylated analog chrysin in the Atlantic killifish. Chemico-Biol Interact. 2006; 164(1-2): 85-92.
23. Walle T, Otake Y, Brubaker JA, Walle UK, Halushka PV. Disposition and metabolism of the favonoidchrysin in normal volunteers. J Clin Pharmacol. 2001; 51: 143-146.
24. Tsuji PA, Walle T. Cytotoxic effects of the dietary flavones chrysin and apigenin in a normal trout liver cell line. Chemico-Biol Interact. 2008; 171(1): 37-44.
25. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer. 2013; 49(6): 1374-1403.
26. Khacha-Ananda S, Tragoolpua K, Chantawannakul P, Tragoolpua Y. Propolis extracts from the northern region of Thailand suppress cancer cell growth through induction of apoptosis pathways. Invest New Drugs. 2016; 34(6): 707-722.
27. Patel S. Emerging adjuvant therapy for cancer: propolis and its constituents. J Diet Suppl. 2006; 13(3): 245-268.
28. Samarghandian S, Afshari JT, Davoodi S. Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line pc-3. Clinics. 2011; 66(6): 1073-1079.
29. Xue C, Chen Y, Hu DN, Iacob C, Lu C, Huang Z. Chrysin induces cell apoptosis in human uveal melanoma cells via intrinsic apoptosis. Oncol Lett. 2016; 12: 4813-4820.
30. Zhang Q, Phan T, Patel PN, Jaskula-Sztul R, Chen H. Chrysin induces cell apoptosis via activation of the p53/Bcl 2/caspase 9 pathway in hepatocellular carcinoma cells. Exp Ther Med. 2016; 12(1): 469-474.
31. Pichichero E, Cicconi R, Mattei M, Muzi MG, Canini A. Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression. Int J Oncol. 2010; 37(4): 973-981.
32. Yu XM, Phan T, Patel PN, Jaskula-Sztul R, Chen H. Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic thyroid carcinoma in vitro and in vivo. Cancer. 2013; 119(4): 774-781.
33. Sun LP, Chen AL, Hung HC, Chien YH, Huang JS, Huang CY, et al. Chrysin: a histone deacetylase 8 inhibitor with anticancer activity and a suitable candidate for the standardization of chinese propolis. J Agric Food Chem. 2012; 60(47): 11748-11758.
34. Rugge M, Fassan M, Graham DY. Epidemiology of gastric cancer. In: Gastric cancer. Principles and practice. Springer, 2015: 23-34.
35. Yang F, Gong L, Jin H, Pi J, Bai H, Wang H, et al. Chrysin-organogermanium (IV) complex induced Colo205 cell apoptosis-associated mitochondrial function and anti-angiogenesis. Scanning. 2015; 37(4): 246-257.
36. Xia Y, Lian S, Khoi PN, Yoon HJ, Joo YE, Chay KO, et al. Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells. PLOS ONE. 2015; 10(4): e0124007.
37. Xia Y, Lian S, Khoi PN, Yoon HJ, Han JY, Oh Chay K, et al. Chrysin inhibits cell invasion by inhibition of Recepteur d'origine Nantais via suppressing early growth response-1 and NF-κB transcription factor activities in gastric cancer cells. Int J Oncol. 2015a; 46: 1835-1843.
38. Catchpole O, Mitchell K, Bloor S, Davis P, Suddes A. Antiproliferative activity of New Zealand propolis and phenolic compounds vs human colorectal adenocarcinoma cells. Fitoterapia. 2015; 106: 167-174.
39. León IE, Cadavid-Vargas JF, Tiscornia I, Porro V, Castelli S, Katkar P, et al. Oxidovanadium (IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model. J Biol Inorg Chem. 2015; 20(7): 1175-1191.
40. Ronnekleiv-Kelly SM, Nukaya M, Díaz-Díaz CJ, Megna BW, Carney PR, Geiger PG, et al. Aryl hydrocarbon receptor-dependent apoptotic cell death induced by the flavonoid chrysin in human colorectal cancer cells. Cancer Lett. 2016; 370(1): 91-99.
41. Bhardwaj M, Kim NH, Paul S, Jakhar R, Han J, Kang SC. 5-hydroxy-7-methoxyflavone triggers mitochondrial-associated cell death via reactive oxygen species signaling in human colon carcinoma cells. PLOS ONE. 2016; 11(4): e0154525.
42. Mohammadian F, Abhari A, Dariushnejad H, Nikanfar A, Pilehvar-Soltanahmadi Y, Zarghami N. Effects of Chrysin-PLGA-PEG nanoparticles on proliferation and gene expression of miRNAs in gastric cancer cell line. Iran J Cancer Prev. 2016; 9(4): e4190.
43. Li X, Huang JM, Wang JN, Xiong XK, Yang XF, Zou F. Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53. Chemico-Biol Interact. 2015; 232: 12-20.
44. Huang C, Wei YX, Shen MC, Tu YH, Wang CC, Huang HC. Chrysin H-Ch.: abundant in Morinda citrifolia fruit water-EtOAc extracts, combined with apigenin synergistically induced apoptosis and inhibited migration in human breast and liver cancer cells. J Agric Food Chem. 2016; 1, 64(21): 4235-4245.
45. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global Cancer Statistics, 2012. Ca Cancer J Clin. 2015; 65(2): 87-108.
46. Weiderpass E, Labrèche F. Malignant tumors of the female reproductive system. Saf Health Work. 2012; 3: 166-180.
47. Lirdprapamongkol K, Sakurai H, Abdelhamed S, Yokoyama S, Maruyama T, Athikomkulchai S, et al. A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse breast cancer cells. Oncol Rep. 2013; 30(5): 2357-2364.
48. ZhaoXC, Cao XC, Liu F, Quan MF, Ren KQ, Cao JG. Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells. Oncol Lett. 2013;5(3): 929-934.
49. Pan D, Li W, Miao H, Yao J, Li Z, Wei L, et al. LW-214, a newly synthesized flavonoid, induces intrinsic apoptosis pathway by down-regulating Trx-1 in MCF-7 human breast cells. Biochem Pharmacol. 2014; 87(4): 598-610.
50. Ding Q, Chen Y, Zhang Q, Guo Y, Huang Z, Dai L, et al. 8 bromo 7 methoxychrysin induces apoptosis by regulating Akt/FOXO3a pathway in cisplatin sensitive and resistant ovarian cancer cells. Mol Med Rep. 2015; 12(4): 5100-5108.
51. Mohammadinejad S, Akbarzadeh A, Rahmati-Yamchi M, Hatam S, Kachalaki S, Zohreh S, et al. Preparation and Evaluation of Chrysin Encapsulated in PLGAPEG Nanoparticles in the T47-D Breast Cancer Cell Line. Asian Pac J Cancer Prev. 2015; 16(9): 3753-3758.
52. Eatemadi A, Daraee H, Aiyelabegan HT, Negahdari B, Rajeian B, Zarghami N. Synthesis and Characterization of chrysin-loaded PCL-PEG-PCL nanoparticle and its effect on breast cancer cell line. Biomed Pharmacother. 2016; 84: 1915-1922.
53. Anari E, Akbarzadeh A, Zarghami N. Chrysin-loaded PLGA-PEG nanoparticles designed for enhanced effect on the breast cancer cell line. Artif Cells Nanomed Biotechnol. 2016; 44(6): 1410-1416.
54. Yang B, Huang J, Xiang T, Yin X, Luo X, Huang J, et al. Chrysin inhibits metastatic potential of human triple-negative breast cancer cells by modulating matrix metalloproteinase-10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway. J Appl Toxicol. 2014; 34: 105-112.
55. Huang C, Chen YJ, Chen WJ, Lin CL, Wei YX, Huang HC. Combined treatment with chrysin and 1,2,3,4,6-penta-O-galloyl-b-D-glucose synergistically inhibits LRP6 and Skp2 activation in triple-negative breast cancer and xenografts. Mol Carcinogen. 2015; 54(12): 1613-1625.
56. Laishram S, Moirangthem DS, Borah JC, Pal BC, Suman P, Gupta SK, et al. Chrysin rich Scutellaria discolor Colebr. induces cervical cancer cell death via the induction of cell cycle arrest and caspase-dependent apoptosis. Life Sci. 2015; 143: 105-113.
57. Warth A, Muley T, Meister M, Stenzinger A, Thomas M, Schirmacher P, et al. The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol. 2012; 30: 1438-1446
58. Shao JJ, Zhang AP, Qin W, Zheng L, Zhu YF, Chen X. AMP-activated protein kinase (AMPK) activation is involved in chrysin-induced growth inhibition and apoptosis in cultured A549 lung cancer cells. Biochem Biophys Res Commun. 2012; 423(3): 448-453.
59. Kasala ER, Boddulurua LN, Baruab CC, Madhanaa RM, Dahiyaa V, Budhania MK, et al. Chemopreventive effect of chrysin, a dietary flavone against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice. Pharmacol Rep. 2016; 68: 310-318.
60. Lim HK, Kim KM, Jeong SY, Choi EK, Jung J. Chrysin increases the therapeutic efficacy of docetaxel and mitigates docetaxel-induced edema. Integr Cancer Ther. 2016: 1-9.
61. Brechbuhlf HM, Kachadourian R, Min E, Chan D, Day BJ. Chrysin enhances doxorubicin-induced cytotoxicity in human lung epithelial cancer cell lines: the role of glutathione. Toxicol Appl Pharmacol. 2012; 1, 258(1): 1-9.
62. Lirdprapamongkol K, Sakurai H, Abdelhamed S, Yokoyama S, Athikomkulchai S, Viriyaroj A, et al. Chrysin overcomes TRAIL resistance of cancer cells through Mcl-1 downregulation by inhibiting STAT3 phosphorylation. Int J Oncol. 2013; 43(1): 329-337.
63. Narayan C, Kumar A. Antineoplastic and immunomodulatory effect of polyphenolic components of Achyranthes aspera (PCA) extract on urethane induced lung cancer in vivo. Mol Biol Rep. 2014; 41(1): 179-191.
How to Cite
Chylińska-Wrzos, P.; Lis-Sochocka, M.; Jodłowska-Jędrych, B. Chrysin and Its Potential Antineoplastic Effect. European Journal of Biological Research 2017, 7, 245-254.
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