The Cytotoxicity and Anticancer Effects of Propolis against the Oral Squamous Cell Carcinoma: In Vitro Study

Mostafa Alam; Kamyar Abbasi; Farzad Nouri; Mohsen Golkar; Reza Ranjbar; Mohesn Yazdanian; Zahra Sadat Hosseini; Elahe Tahmasebi; Hamid Tebyaniyan

doi:10.3889/oamjms.2022.10882

Authors

Mostafa Alam Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Kamyar Abbasi Department of Prosthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Farzad Nouri Department of Oral and Maxillofacial Surgery, School of Dentistry, Zahedan University of Medical Sciences, Zahedan, Iran
Mohsen Golkar Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Reza Ranjbar Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran; Department of Oral and Maxillofacial Surgery, School of Dentistry, Baqiyatallah University of Medical Sciences, Tehran, Iran
Mohesn Yazdanian Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
Zahra Sadat Hosseini Varamin Pishva Branch, Islamic Azad University, Tehran, Iran; 7Islamic Azad University, Tehran, Iran
Elahe Tahmasebi Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
Hamid Tebyaniyan Islamic Azad University, Tehran, Iran

DOI:

https://doi.org/10.3889/oamjms.2022.10882

Keywords:

Propolis, Cell cytotoxicity, Apoptosis, Oral squamous cell carcinoma

Abstract

Background and aim: A wide range of therapeutic properties, including anti-cancer properties, are attributed to propolis, a resinous product obtained from several plants that possess a variety of medicinal properties. A study on honeybee-produced propolis showed that in mice, it showed a significant reduction in the progression of squamous cell carcinoma in the head and neck, but in humans, its role in HNSCC remains unclear.

Method and materials: Propolis was sampled from two types of Iranian. Extraction was done using ethanolic extracts of propolis. The cll viability was evaluated by MTT assay. Cancer cell lines were assessed for gene expression, such as mmp-2, mmp-9, bax, and bcl-2.

Results: Increased sample concentrations reduced cell viability but did not cause significant cytotoxicity. A RT-PCR indicated that the Khalkhal sample produced more effects among the two samples, and the level of bax mRNA gene expression in the Khalkhal sample was increased. With an increasing concentration of Khalkhal samples, the expression increased. Increasing Khalkhal sample concentration also reduced mRNA levels of bcl-2, mmp-2, and mmp-9.

Conclusion: Khalkhal’s propolis can be considered a suitable sample for the study of antiapoptotic and proapoptotic gene expression. Additionally, it can be used as a potential candidate for inhibiting the proliferation and spread of oral cancer cells.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Gupta B, Johnson NW, Kumar N. Global epidemiology of head and neck cancers: A continuing challenge. Oncology. 2016;91(1):13-23. https://doi.org/10.1159/000446117 PMid:27245686 DOI: https://doi.org/10.1159/000446117

Niyomtham N, Koontongkaew S, Yingyongnarongkul BE, Utispan K. Apis mellifera propolis enhances apoptosis and invasion inhibition in head and neck cancer cells. Peer J. 2021;9:e12139. https://doi.org/10.7717/peerj.12139 PMid:34589307 DOI: https://doi.org/10.7717/peerj.12139

Kuno T, Tsukamoto T, Hara A, Tanaka T. Cancer chemoprevention through the induction of apoptosis by natural compounds. J Biophys Chem. 2012;3(2):18. https://doi.org/10.4236/jbpc.2012.32018 DOI: https://doi.org/10.4236/jbpc.2012.32018

Maioral MF, do Nascimento Bodack C, Stefanes NM, Bigolin Á, Mascarello A, Chiaradia-Delatorre LD, et al. Cytotoxic effect of a novel naphthylchalcone against multiple cancer cells focusing on hematologic malignancies. Biochimie. 2017;140:48-57. https://doi.org/10.1016/j.biochi.2017.06.004 PMid:28610775 DOI: https://doi.org/10.1016/j.biochi.2017.06.004

Tan W, Lu J, Huang M, Li Y, Chen M, Wu G, et al. Anti-cancer natural products isolated from chinese medicinal herbs. Chin Med. 2011;6(1):27. https://doi.org/10.1186/1749-8546-6-27 PMid:21777476 DOI: https://doi.org/10.1186/1749-8546-6-27

Ramzan M, Karobari MI, Heboyan A, Mohamed RN, Mustafa M, Basheer SN, et al. Synthesis of silver nanoparticles from extracts of wild ginger (Zingiber zerumbet) with antibacterial activity against selective multidrug resistant oral bacteria. Molecules. 2022;27(6):2007. https://doi.org/10.3390/molecules27062007 PMid:35335369 DOI: https://doi.org/10.3390/molecules27062007

Heboyan A, Avetisyan A, Karobari MI, Marya A, Khurshid Z, Rokaya D, et al. Tooth root resorption: A review. Sci Prog. 2022;105(3):368504221109217. https://doi.org/10.1177/00368504221109217 PMid:35759366 DOI: https://doi.org/10.1177/00368504221109217

Bhargava P, Grover A, Nigam N, Kaul A, Doi M, Ishida Y, et al. Anticancer activity of the supercritical extract of Brazilian green propolis and its active component, artepillin C: Bioinformatics and experimental analyses of its mechanisms of action. Int J Oncol. 2018;52(3):925-32. https://doi.org/10.3892/ijo.2018.4249 PMid:29393408 DOI: https://doi.org/10.3892/ijo.2018.4249

Kujumgiev A, Tsvetkova I, Serkedjieva Y, Bankova V, Christov R, Popov S. Antibacterial, antifungal and antiviral activity of propolis of different geographic origin. J Ethnopharmacol. 1999;64(3):235-40. https://doi.org/10.1016/s0378-8741(98)00131-7 PMid:10363838 DOI: https://doi.org/10.1016/S0378-8741(98)00131-7

Pepeljnjak S, Jalsenjak I, Maysinger D. Flavonoid content in propolis extracts and growth inhibition of Bacillus subtilis. Pharmazie. 1985;40(2):122-3. PMid:3923500

Velikova M, Bankova V, Tsvetkova I, Kujumgiev A, Marcucci MC. Antibacterial ent-kaurene from Brazilian propolis of native stingless bees. Fitoterapia. 2000;71(6):693-6. https://doi.org/10.1016/s0367-326x(00)00213-6 PMid:11077178 DOI: https://doi.org/10.1016/S0367-326X(00)00213-6

Gao W, Wu J, Wei J, Pu L, Guo C, Yang J, et al. Brazilian green propolis improves immune function in aged mice. J Clin Biochem Nutr. 2014;55(1):7-10. https://doi.org/10.3164/jcbn.13-70 PMid:25120274 DOI: https://doi.org/10.3164/jcbn.13-70

Khayyal MT, El-Ghazaly MA, El-khatib AS. Mechanisms involved in the antiinflammatory effect of propolis extract. Drugs Exp Clin Res. 1993;19(5):197-203. PMid:7513636

Wang L, Yang L, Debidda M, Witte D, Zheng Y. Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Proc Natl Acad Sci U S A. 2007;104(4):1248. https://doi.org/10.1073/pnas.0609149104 PMid:17227869 DOI: https://doi.org/10.1073/pnas.0609149104

Sartori G, Pesarico AP, Pinton S, Dobrachinski F, Roman SS, Pauletto F, et al. Protective effect of brown Brazilian propolis against acute vaginal lesions caused by herpes simplex virus Type 2 in mice: Involvement of antioxidant and anti-inflammatory mechanisms. Cell Biochem Funct. 2012;30(1):1-10. https://doi.org/10.1002/cbf.1810 PMid:22025285 DOI: https://doi.org/10.1002/cbf.1810

Kashi TS, Kermanshahi RK, Erfan M, Dastjerdi EV, Rezaei Y, Tabatabaei FS. Evaluating the in-vitro antibacterial effect of Iranian propolis on oral microorganisms. Iran J Pharm Res. 2011;10(2):363-8. PMid:24250366

Fauzi AN, Norazmi MN, Yaacob NS. Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines. Food Chem Toxicol. 2011;49(4):871-8. https://doi.org/10.1016/j.fct.2010.12.010 PMid:21167897 DOI: https://doi.org/10.1016/j.fct.2010.12.010

Ghashm AA, Othman NH, Khattak MN, Ismail NM, Saini R. Antiproliferative effect of Tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines. BMC Complement Altern Med. 2010;10(1):49. https://doi.org/10.1186/1472-6882-10-49 PMid:20840769 DOI: https://doi.org/10.1186/1472-6882-10-49

Messerli SM, Ahn MR, Kunimasa K, Yanagihara M, Tatefuji T, Hashimoto K, et al. Artepillin C (ARC) in Brazilian green propolis selectively blocks oncogenic PAK1 signaling and suppresses the growth of NF tumors in mice. Phytother Res. 2009;23(3):423-7. https://doi.org/10.1002/ptr.2658 PMid:19003952 DOI: https://doi.org/10.1002/ptr.2658

Sawicka D, Car H, Borawska MH, Nikliński J. The anticancer activity of propolis. Folia Histochem Cytobiol. 2012;50(1):25-37. https://doi.org/10.2478/18693 PMid:22532133 DOI: https://doi.org/10.5603/FHC.2012.0004

Wadhwa R, Nigam N, Bhargava P, Dhanjal JK, Goyal S, Grover A, et al. Molecular characterization and enhancement of anticancer activity of caffeic acid phenethyl ester by γ _cyclodextrin. J Cancer. 2016;7(13):1755-71. https://doi.org/10.7150/jca.15170 PMid:27698914 DOI: https://doi.org/10.7150/jca.15170

Rao CV, Desai D, Simi B, Kulkarni N, Amin S, Reddy BS. Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon. Cancer Res. 1993;53(18):4182-8. PMid:8364913

Khacha-Ananda S, Tragoolpua K, Chantawannakul P, Tragoolpua Y. Antioxidant and anti-cancer cell proliferation activity of propolis extracts from two extraction methods. Asian Pac J Cancer Prev. 2013;14(11):6991-5. https://doi.org/10.7314/apjcp.2013.14.11.6991 PMid:24377638 DOI: https://doi.org/10.7314/APJCP.2013.14.11.6991

Machado BA, Silva RP, de Abreu Barreto G, Costa SS, da Silva DF, Brandão HN, et al. Chemical composition and biological activity of extracts obtained by supercritical extraction and ethanolic extraction of brown, green and red propolis derived from different geographic regions in Brazil. PLoS One. 2016;11(1):e0145954. https://doi.org/10.1371/journal.pone.0145954 PMid:26745799 DOI: https://doi.org/10.1371/journal.pone.0145954

Burdock GA. Review of the biological properties and toxicity of bee propolis (propolis). Food Chem Toxicol. 1998;36(4):347-63. https://doi.org/10.1016/s0278-6915(97)00145-2 PMid:9651052 DOI: https://doi.org/10.1016/S0278-6915(97)00145-2

Motallaei MN, Yazdanian M, Tebyanian H, Tahmasebi E, Alam M, Abbasi K, et al. The current strategies in controlling oral diseases by herbal and chemical materials. Evid Based Complement Alternat Med. 2021;2021:3423001. https://doi.org/10.1155/2021/3423001 PMid:34471415 DOI: https://doi.org/10.1155/2021/3423001

Benguedouar L, Boussenane HN, Wided K, Alyane M, Rouibah H, Lahouel M, et al. Efficiency of propolis extract against mitochondrial stress induced by antineoplasic agents (doxorubicin and vinblastin) in rats. 2008;46(2):112-9. PMid:18335809

Chen CN, Weng MS, Wu CL, Lin JK. Comparison of radical scavenging activity, cytotoxic effects and apoptosis induction in human melanoma cells by Taiwanese propolis from different sources. Evid Based Complement Alternat Med. 2004;1(2):175-85. https://doi.org/10.1093/ecam/neh034 PMid:15480443 DOI: https://doi.org/10.1093/ecam/neh034

Kumar S, Sharma VK, Yadav S, Dey S. Antiproliferative and apoptotic effects of black turtle bean extracts on human breast cancer cell line through extrinsic and intrinsic pathway. Chem Cent J. 2017;11(1):56. https://doi.org/10.1186/s13065-017-0281-5 PMid:29086840 DOI: https://doi.org/10.1186/s13065-017-0281-5

Li H, Qiu Z, Li F, Wang C. The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis. Oncol Lett. 2017;14(5):5865-70. https://doi.org/10.3892/ol.2017.6924 PMid:29113219 DOI: https://doi.org/10.3892/ol.2017.6924

Khurshid Z, Naseem M, Zafar MS, Najeeb S, Zohaib S. Propolis: A natural biomaterial for dental and oral healthcare. J Dent Res Dent Clin Dent Prospects. 2017;11(4):265-74. https://doi.org/10.15171/joddd.2017.046 PMid:29354255

Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013.

Heboyan A, Avetisyan A, Skallevold HE, Rokaya D, Marla V, Vardanyan A. Occurrence of recurrent aphthous stomatitis (RAS) as a rare oral manifestation in a patient with Gilbert’s syndrome. Case Rep Dent. 2021;2021:6648729. https://doi.org/10.1155/2021/6648729 PMid:33953989 DOI: https://doi.org/10.1155/2021/6648729

Heboyan A, Syed AU, Rokaya D, Cooper PR, Manrikyan M, Markaryan M. Cytomorphometric analysis of inflammation dynamics in the periodontium following the use of fixed dental prostheses. Molecules. 2020;25(20):4650. https://doi.org/10.3390/molecules25204650 PMid:33053882 DOI: https://doi.org/10.3390/molecules25204650

Yadalam PK, Sivasankari T, Rengaraj S, Mugri MH, Sayed M, Khan SS, et al. Gene interaction network analysis reveals IFI44L as a drug target in rheumatoid arthritis and periodontitis. Molecules. 2022;27(9):2749. https://doi.org/10.3390/molecules27092749 PMid:35566100 DOI: https://doi.org/10.3390/molecules27092749

van Oijen MG, Slootweg PJ. Oral field cancerization: Carcinogen-induced independent events or micrometastatic deposits? Cancer Epidemiol Biomarkers Prev. 2000;9(3):249-56. PMid:10750662

Yilmaz B, Erdal B. Anti-cancer activities of curcumin and propolis extracts on MCF-7 breast cancer cell line model. Medicine. 2020;9(4):877-84. DOI: https://doi.org/10.5455/medscience.2020.06.098

Banskota AH, Nagaoka T, Sumioka LY, Tezuka Y, Awale S, Midorikawa K, et al. Antiproliferative activity of the Netherlands propolis and its active principles in cancer cell lines. J Ethnopharmacol. 2002;80(1):67-73. https://doi.org/10.1016/s0378-8741(02)00022-3 PMid:11891088 DOI: https://doi.org/10.1016/S0378-8741(02)00022-3

Zheng Y, Wu Y, Chen X, Jiang X, Wang K, Hu F. Chinese propolis exerts anti-proliferation effects in human melanoma cells by targeting NLRP1 inflammatory pathway, inducing apoptosis, cell cycle arrest, and autophagy. Nutrients. 2018;10(9):1170. https://doi.org/10.3390/nu10091170 PMid:30149677 DOI: https://doi.org/10.3390/nu10091170

Jiang XS, Xie HQ, Li CG, You MM, Zheng YF, Li GQ, et al. Chinese propolis inhibits the proliferation of human gastric cancer cells by inducing apoptosis and cell cycle arrest. Evid Based Complement Alternat Med. 2020;2020:2743058. https://doi.org/10.1155/2020/2743058 PMid:32774408 DOI: https://doi.org/10.1155/2020/2743058

Russo A, Cardile V, Sanchez F, Troncoso N, Vanella A, Garbarino JA. Chilean propolis: Antioxidant activity and antiproliferative action in human tumor cell lines. Life Sci. 2004;76(5):545-58. https://doi.org/10.1016/j.lfs.2004.07.019 PMid:15556167 DOI: https://doi.org/10.1016/j.lfs.2004.07.019

Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, et al. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 2015;35:S78-103. https://doi.org/10.1016/j.semcancer.2015.03.001 PMid:25936818 DOI: https://doi.org/10.1016/j.semcancer.2015.03.001

Findley HW, Gu L, Yeager AM, Zhou M. Expression and regulation of Bcl-2, Bcl-xl, and bax correlate with p53 Status and sensitivity to apoptosis in childhood acute lymphoblastic leukemia. Blood. 1997;89(8):2986-93. PMid:9108419 DOI: https://doi.org/10.1182/blood.V89.8.2986

Fan H, Li X, Wang W, Lai Q, Tang X, Gao D, et al. Effects of NMDA-receptor antagonist on the expressions of Bcl-2 and bax in the subventricular zone of neonatal rats with hypoxia-ischemia brain damage. Cell Biochem Biophys. 2015;73(2):323-30. https://doi.org/10.1007/s12013-015-0586-8 PMid: 27352318 DOI: https://doi.org/10.1007/s12013-015-0586-8

Youle RJ, Strasser A. The BCL-2 protein family: Opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9(1):47-59. https://doi.org/10.1038/nrm2308 PMid:18097445 DOI: https://doi.org/10.1038/nrm2308