Synergistic Cytotoxic Effect of Honey Bee Venom and Cisplatin on Tongue Squamous Cell Carcinoma Cell Line

Authors

  • Sabreen Amar Department of Oral and Maxillofacial Pathology https://orcid.org/0000-0003-1858-1993
  • Amr Helmy Mustafa El-Bolok Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Minya University, Minya, Egypt
  • Sherif Farouk El-Gayar Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Minya University, Minya, Egypt
  • Maii Ibrahim Sholkamy Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Minya University, Minya, Egypt

DOI:

https://doi.org/10.3889/oamjms.2021.7672

Keywords:

Honey bee venom, Cisplatin, SCC-25 cells, Apoptosis

Abstract

BACKGROUND: Tongue cancer is one of the most common head and neck cancers in the world. Nowadays, natural compounds are important resources of many anti-cancer drugs. Venom from honey bees possesses potent anti-cancer activities. Cisplatin is a chemotherapeutic drug that has been used for decades to treat cancer cells. Recently, combination therapy has been a popular treatment choice for cancer patients.

AIM: This study was conducted to evaluate the synergistic cytotoxic effect of honey bee venom (BV) and cisplatin on tongue squamous cell carcinoma 25 (SCC-25) cell lines.

METHODS: The cytotoxic effect was determined using methyl thiazol tetrazolium assay, microscopic examination, real-time polymerase chain reaction (RT-PCR), and statistical analysis.

RESULTS: The findings revealed that the cytotoxic potential of the tested drugs on SCC-25 cells was dose-dependent. Microscopic examination showed that BV and cisplatin alone and in combination mainly produced apoptotic cell death. Regarding RT-PCR results, P53 and caspase-3 expression levels were significantly increased in SCC-25-treated cells (p = 0.0001).

CONCLUSION: The combined use of BV and cisplatin induced a marked synergistic cytotoxic effect on SCC-25 cell line.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, 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(3):209-49. http://doi.org/10.3322/caac.21660 PMid:33538338

Yosefof E, Hilly O, Stern S, Bachar G, Shpitzer T, Mizrachi A. Squamous cell carcinoma of the oral tongue: Distinct epidemiological profile disease. Head Neck. 2020;42(9):2316-20. http://doi.org/10.1002/hed.26177 PMid:32320105

Farah CS. Oral mucosal malignancies. In: Balasubramaniam R, McCullough MJ, editors. Contemporary Oral Medicine: A Comprehensive Approach to Clinical Practice. Cham: Springer International Publishing; 2019. p. 1249-436.

Cramer JD, Burtness B, Le AT, Ferris RL. The changing therapeutic landscape of head and neck cancer. Nat Rev Clin Oncol. 2019;16(11):669-83. http://doi.org/10.1038/s41571-019-0227-z PMid:31189965

Rayan A, Raiyn J, Falah M. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity. PLoS One. 2017;12(11):e0187925. http://doi.org/10.1371/journal.pone.0187925 PMid:29121120

Frangieh J, Salma Y, Haddad K, Mattei C, Legros C, Fajloun Z, et al. First characterization of the venom from Apis Mellifera syriaca, a honey bee from the Middle East region. Toxins. 2019;11(4):191. http://doi.org/10.3390/toxins11040191 PMid:30935025

Kim KH, Kim M, Lee J, Jeon HN, Kim SH, Bae H. Comparison of the protective effects of bee venom extracts with varying PLA2 compositions in a mouse model of parkinson’s disease. Toxins. 2019;11(6):358. http://doi.org/10.3390/toxins11060358 PMid:31248167

El Bakary NM, Alsharkawy AZ, Shouaib ZA, Barakat EM. Role of bee venom and melittin on restraining angiogenesis and metastasis in γ-irradiated solid ehrlich carcinoma-bearing mice. Integr Cancer Ther. 2020;19:1534735420944476.

Yaacoub C, Rifi M, El-Obeid D, Mawlawi H, Sabatier JM, Coutard B, et al. The cytotoxic effect of Apis mellifera venom with a synergistic potential of its two main components melittin and PLA2 on colon cancer HCT116 cell lines. Molecules. 2021;26(8):2264. http://doi.org/10.3390/molecules26082264 PMid:33919706

Wehbe R, Frangieh J, Rima M, El Obeid D, Sabatier JM, Fajloun Z. Bee Venom: Overview of main compounds and bioactivities for therapeutic interests. Molecules (Basel, Switzerland). 2019;24(16):2997. http://doi.org/10.3390/molecules24162997 PMid:31430861

Qi L, Luo Q, Zhang Y, Jia F, Zhao Y, Wang F. Advances in toxicological research of the anticancer drug cisplatin. Chem Res Toxicol. 2019;32(8):1469-86. http://doi.org/10.1021/acs.chemrestox.9b00204 PMid:31353895

Kleih M, Böpple K, Dong M, Gaißler A, Heine S, Olayioye MA, et al. Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells. Cell Death Dis. 2019;10(11):1-12.

Oun R, Moussa YE, Wheate NJ. The side effects of platinum-based chemotherapy drugs: A review for chemists. Dalton Trans. 2018;47(19):6645-53. http://doi.org/10.1039/c8dt00838h PMid:29632935

Gajski G, Čimbora-Zovko T, Rak S, Osmak M, Garaj-Vrhovac V. Antitumour action on human glioblastoma A1235 cells through cooperation of bee venom and cisplatin. Cytotechnology. 2016;68(4):1197-205. http://doi.org/10.1007/s10616-015-9879-4 PMid:25916941

Ciccarone F, De Falco P, Ciriolo MR. Aconitase 2 sensitizes MCF-7 cells to cisplatin eliciting P53-mediated apoptosis in a ROS-dependent manner. Biochem Pharmacol. 2020;180:114202. http://doi.org/10.1016/j.bcp.2020.114202 PMid:32818504

Yadav P, Yadav R, Jain S, Vaidya A. Caspase-3, a primary target for natural and synthetic compounds for cancer therapy. Chem Biol Drug Des. 2021;98(1):144-65. http://doi.org/10.1111/cbdd.13860 PMid:33963665

Xu X, Lai Y, Hua ZC. Apoptosis and apoptotic body: Disease message and therapeutic target potentials. Biosci Rep. 2019;39(1):BSR20180992. http://doi.org/10.1042/BSR20180992 PMid:30530866

Arandjelovic S, Ravichandran KS. Phagocytosis of apoptotic cells in homeostasis. Nat Immunol. 2015;16(9):907-17. http://doi.org/10.1038/ni.3253 PMid:26287597

Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY), 2016;8(4):603. http://doi.org/10.18632/aging.100934 PMid:27019364

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. http://doi.org/10.3322/caac.21262 PMid:25651787

Pires FR, Ramos AB, de Oliveira JB, Tavares AS, da Luz PS, dos Santos TC. Oral squamous cell carcinoma: Clinicopathological features from 346 cases from a single oral pathology service during an 8-year period. J Appl Oral Sci. 2013;21(5):460-7. http://doi.org/10.1590/1679-775720130317 PMid:24212993

Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist. 2019;2(2):141-60. http://doi.org/10.20517/cdr.2019.10 PMid:34322663

Carpena M, Nuñez-Estevez B, Soria-Lopez A, Simal-Gandara J. Bee Venom: An updating review of its bioactive molecules and its health applications. Nutrients. 2020;12(11):3360. http://doi.org/10.3390/nu12113360 PMid:33142794

Lee HS, Kim YS, Lee KS, Seo HS, Lee CY, Kim KK. Detoxification of bee venom increases its anti-inflammatory activity and decreases its cytotoxicity and allergenic activity. Appl Biochem Biotechnol. 2021;193(12):4068-82. http://doi.org/10.1007/s12010-021-03653-2 PMid:34542820

Zhu H, Luo H, Zhang W, Shen Z, Hu X, Zhu X. Molecular mechanisms of cisplatin resistance in cervical cancer. Drug Design Dev Ther. 2016;10:1885. http://doi.org/10.2147/DDDT.S106412 PMid:27354763

Alonezi S, Tusiimire J, Wallace J, Dufton MJ, Parkinson JA, Young LC, et al. Metabolomic profiling of the synergistic effects of melittin in combination with cisplatin on ovarian cancer cells. Metabolites. 2017;7(2):14. http://doi.org/10.3390/metabo7020014 PMid:28420117

He Y, Zhu Q, Chen M, Huang Q, Wang W, Li Q, et al. The changing 50% inhibitory concentration (IC50) of cisplatin: A pilot study on the artifacts of the MTT assay and the precise measurement of density-dependent chemoresistance in ovarian cancer. Oncotarget. 2016;7(43):70803-21. http://doi.org/10.18632/oncotarget.12223 PMid:27683123

Goldar S, Khaniani MS, Derakhshan SM, Baradaran B. Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac J Cancer Prev. 2015;16(6):2129-44. http:// doi.org/10.7314/apjcp.2015.16.6.2129 PMid:25824729

Kiraz Y, Adan A, Yandim MK, Baran Y. Major apoptotic mechanisms and genes involved in apoptosis. Tumor Biol. 2016;37(7):8471-86. http://doi.org/10.1007/s13277-016-5035-9 PMid:27059734

Follis AV, Llambi F, Merritt P, Chipuk JE, Green DR, Kriwacki RW. Pin1-induced proline isomerization in cytosolic P53 mediates BAX activation and apoptosis. Mol Cell. 2015;59(4):677-84. http://doi.org/10.1016/j.molcel.2015.06.029 PMid:26236013

Jo DW, Kim YK, Yun PY. The influence of P53 mutation status on the anti-cancer effect of cisplatin in oral squamous cell carcinoma cell lines. J Korean Assoc Oral Maxillofac Surg. 2016;42(6):337-44. http://doi.org/10.5125/jkaoms.2016.42.6.337 PMid:28053903

Downloads

Published

2021-11-29

How to Cite

1.
Amar S, El-Bolok AHM, El-Gayar SF, Sholkamy MI. Synergistic Cytotoxic Effect of Honey Bee Venom and Cisplatin on Tongue Squamous Cell Carcinoma Cell Line. Open Access Maced J Med Sci [Internet]. 2021 Nov. 29 [cited 2026 Oct. 16];9(B):1739-44. Available from: https://oamjms.eu/index.php/mjms/article/view/7672