Dergiler / Sakarya Tıp Dergisi / 2026 / Volume: 16 Issue: 2

Dose-Dependent Effects of Bee Venom (Apis mellifera anatoliaca) on Cell Viability and Migration in A549 Lung Adenocarcinoma Cells

Zeynep Yürekli Sarar(HATAY MUSTAFA KEMAL UNIVERSITY, TAYFUR ATA SOKMEN MEDICAL SCHOOL, DEPARTMENT OF MEDICAL BIOLOGY)0009-0002-2609-7755
Meral Urhan Küçük(HATAY MUSTAFA KEMAL UNIVERSITY, TAYFUR ATA SOKMEN MEDICAL SCHOOL, DEPARTMENT OF MEDICAL BIOLOGY)0000-0003-1704-1370
Aziz Gül(HATAY MUSTAFA KEMAL UNIVERSITY, FACULTY OF AGRICULTURE, DEPARTMENT OF ANIMAL SCIENCE)0000-0003-1158-5018
Tarık Mecit(BIRUNI UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF PHYSIOLOGY)0000-0002-3816-134X
İlter Değer(HATAY MUSTAFA KEMAL UNIVERSITY, TAYFUR ATA SOKMEN MEDICAL SCHOOL, DEPARTMENT OF PHARMACOLOGY)0000-0002-5701-9007
Aysel Günay Sakar(HATAY SCIENCE AND ART CENTER (BILSEM))0009-0000-7260-2594
Güven Yenmiş(HATAY MUSTAFA KEMAL UNIVERSITY, TAYFUR ATA SOKMEN MEDICAL SCHOOL, DEPARTMENT OF MEDICAL BIOLOGY)0000-0002-6688-9725
Sayfa
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Yayın Tarihi
2026-06-30
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Conclusions: These findings indicate that BV modulates cell migration in A549 cells without inducing pronounced cytotoxicity and may exhibit potential antimetastatic properties at higher concentrations.

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Amaç & Hipotez:Objective: Lung cancer remains one of the leading causes of cancer-related mortality worldwide, and the emergence of resistance to existing therapies together with severe adverse effects necessitates the investigation of novel therapeutic agents.
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Temel Bulgular & Veri:In this study, the effects of bee venom (BV) derived from Apis mellifera anatoliaca on the non-small cell lung cancer cell line A549 were evaluated with respect to cell viability and cell migration.
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Sonuç & Katkı:Conclusions: These findings indicate that BV modulates cell migration in A549 cells without inducing pronounced cytotoxicity and may exhibit potential antimetastatic properties at higher concentrations.
🔬Tür:Research Article
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Apis mellifera anatoliaca · A549 · Non-small cell lung cancer

Abstract

Objective: Lung cancer remains one of the leading causes of cancer-related mortality worldwide, and the emergence of resistance to existing therapies together with severe adverse effects necessitates the investigation of novel therapeutic agents. In this study, the effects of bee venom (BV) derived from Apis mellifera anatoliaca on the non-small cell lung cancer cell line A549 were evaluated with respect to cell viability and cell migration. Methods and Results: Cell viability was assessed using the MTT assay following treatment with BV at concentrations of 8, 16, and 32 ng/mL. At the sixth hour, statistically significant differences were detected among the experimental groups (p < 0.0001). While no significant difference was observed between the control group and the 8 ng/mL group (p = 0.83), treatment with 16 and 32 ng/mL BV resulted in a significant decrease in cell viability (p < 0.0001 for both). Time-course analyses performed using lower concentrations (0.5–12 ng/mL) revealed no statistically significant differences at the 6th, 18th, or 48th hours (p > 0.05); however, a limited but significant difference was observed at the 24th hour (p = 0.02). According to two-way repeated-measures ANOVA, BV concentration did not exert a significant main effect on cell viability (F(7,16) = 0.53; p = 0.80), whereas the time factor showed a strong and significant effect (F(3,41,54,52) = 146.3; p < 0.0001). Cell migration was evaluated using a wound-healing assay, which revealed a dose-dependent biphasic effect. Migration increased at lower concentrations (4 ng/mL: 91.31 ± 1.76%; 8 ng/mL: 85.83 ± 4.17%) compared with the control group (70.26 ± 7.96%), whereas higher concentrations significantly suppressed migration (12 ng/mL: 58.16 ± 6.42%; 32 ng/mL: 54.53 ± 8.05%; p < 0.05). Conclusions: These findings indicate that BV modulates cell migration in A549 cells without inducing pronounced cytotoxicity and may exhibit potential antimetastatic properties at higher concentrations.

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Bu Makaleye Atıf Yap

Sarar, Z. Y., Küçük, M. U., Gül, A., Mecit, T., Değer, İ., Sakar, A. G., Yenmiş, G. (2026). Dose-Dependent Effects of Bee Venom (Apis mellifera anatoliaca) on Cell Viability and Migration in A549 Lung Adenocarcinoma Cells. Sakarya Tıp Dergisi, Volume: 16 Issue: 2. https://doi.org/10.31832/smj.1866646

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Kaynakça (41)

  1. International Agency for Research on Cancer. (2020). GLOBOCAN 2020: Cancer today. World Health Organization[Online] Available: https://gco.iarc.fr/today
  2. Ibrahim HM, Alessa J, Khalil HB, Bekhet GA, Khalifa A. Synergistic anti-cancer activity of melittin and erlotinib in non-small cell lung cancer. Int J Mol Sci. 2025;26(7):2903. doi:10.3390/ijms26072903.
  3. Viegas S, Ladeira C, Costa-Veiga A, Perelman J, Gajski G. Forgotten public health impacts of cancer: an overview. Arh Hig Rada Toksikol. 2017;68(4):287–97. doi:10.1515/aiht-2017-68-3005.
  4. Bagyalakshmi B, Priyadarshini SL, Balamurugan A. Anticancer activity of bee venom against lung cancer cell line (A549 cells) enhanced by iron oxide nanoparticles synthesized from Syzygium aromaticum. J Drug Deliv Ther. 2019;9(3-s):248–54. doi:10.22270/jddt.v9i3-s.2983.
  5. Wild CP, Weiderpass E, Stewart BW (Eds.) (2020). World cancer report: Cancer research for cancer prevention. International Agency for Research on Cancer.
  6. Gajski G, Leonova E, Sjakste N. Bee venom: composition and anticancer properties. J Toxins. 2024;16(3):117. doi:10.3390/toxins16030117.
  7. Fratellone PM, Tsimis F, Fratellone G. Apitherapy products for medicinal use. J Altern Complement Med. 2016;2(12):1020–2. doi:10.1089/acm.2015.0346.
  8. Cherniack EP. Bugs as drugs, part two: worms, leeches, scorpions, snails, ticks, centipedes, and spiders. Altern Med Rev. 2011;16(1):50–8.
  9. Mehta RG, Murillo G, Naithani R, Peng X. Cancer chemoprevention by natural products: how far have we come?. Pharm Res. 2010;27(6), 950–61. doi:10.1007/s11095-010-0085-y.
  10. Siddiqui SA, Li C, Aidoo OF, Fernando I, Haddad MA, Pereira JAM, et al. Unravelling the potential of insects for medicinal purposes: a comprehensive review. Heliyon. 2023;9(5):e15938. doi:10.1016/j.heliyon.2023.e15938.
  11. Bordon KCF, Cologna CT, Fornari-Baldo EC, Pinheiro-Júnior EL, Cerni FA, Amorim FG, et al. From animal poisons and venoms to medicines: achievements, challenges and perspectives in drug discovery. Front Pharmacol. 2020;11:1132. doi:10.3389/fphar.2020.01132.
  12. Herzig V, Cristofori-Armstrong B, Israel MR, Nixon SA, Vetter I, King GF. Animal toxins: nature’s evolutionary-refined toolkit for basic research and drug discovery. Biochem Pharmacol. 2020;181:114096. doi:10.1016/j.bcp.2020.114096.
  13. Khalil A, Elesawy BH, Ali TM, Ahmed OM. Bee venom: from venom to drug. Molecules. 2021;26(16):4941. doi:10.3390/molecules26164941.
  14. Sjakste N, Gajski G. A review on genotoxic and genoprotective effects of biologically active compounds of animal origin. J Toxins. 2023;15(2):165. doi:10.3390/toxins15020165.
  15. Carpena M, Nuñez-Estevez B, Soria-Lopez A, Simal-Gandara J. Bee venom: an updating review of its bioactive molecules and health applications. Nutrients. 2020;12(11):3360. doi:10.3390/nu12113360.
  16. Zhang S, Liu Y, Ye Y, Wang XR, Lin LT, Xiao LY, et al. Bee venom therapy: potential mechanisms and therapeutic applications. Toxicon. 2018;64–73. doi:10.1016/j.toxicon.2018.04.012.
  17. Ahmed O, Fahim H, Mahmoud A, Ahmed EAE. Bee venom and hesperidin mitigate Freund’s adjuvant-induced arthritis. Arch Rheumatol. 2018;33(2):198–212. doi:10.5606/ArchRheumatol.2018.6519.
  18. Wehbe R, Frangieh J, Rima M, El Obeid D, Sabatier JM, Fajloun JMZ. Bee venom: overview of main compounds and bioactivities for therapeutic interests. Molecules (Basel, Switzerland). 2019;24(16):2997. doi:10.3390/molecules24162997.
  19. Šuligoj M. Origins and development of apitherapy and apitourism. J Apic Res. 2021;60(3):369–74. doi:10.1080/00218839.2021.1874178.
  20. Hellner M, Winter D, von Georgi R, Münstedt K. Apitherapy: usage and experience in German beekeepers. eCAM. 2008;5(4):475–9. doi:10.1093/ecam/nem052.
  21. Son DJ, Lee JW, Lee YH, Song HS, Lee CK, Hong JT. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Ther. 2007;115(2):246–70. doi:10.1016/j.pharmthera.2007.04.004.
  22. Bagyalakshmi B, Priyadarshini SL, Balamurugan A. Anticancer activity of bee venom against lung cancer cell line (A549 cells). J Drug Deliv Ther. 2019;9(3-s):248–254. doi:10.22270/jddt.v9i3-s.2983.
  23. Terwilliger TC, Weissman L, Eisenberg D. Structure of melittin crystals and implications for lytic activity. Biophys J. 1982;37(1):353–61. doi:10.1016/S0006-3495(82)84683-3.
  24. Terwilliger TC, Eisenberg D. The structure of melittin II: interpretation. J Biol Chem. 1982;257(11):6016–22.
  25. Terwilliger TC, Eisenberg D. The structure of melittin I: structure determination. J Biol Chem. 1982;257(11):6010–5.
  26. Lee G, Bae H. Bee venom phospholipase A2. Toxins. 2016;8(2):48. doi:10.3390/toxins8020048.
  27. Habermann E. Neurotoxicity of apamin and MCD peptide. Naunyn-Schmiedeb. Arch. Pharmacol. 1977;300(2):189–91. doi:10.1007/BF00505050.
  28. Habermann E. Apamin. Pharmacol Ther. 1984;25(2):255–70. doi:10.1016/0163-7258(84)90046-9.
  29. Hider RC, Ragnarsson U. Proposal for the structure of apamin. FEBS Lett. 1980;111(1):189–93. doi:10.1016/0014-5793(80)80790-3.
  30. Dotimas EM, Hamid KR, Hider RC, Ragnarsson U. Isolation and structure analysis of bee venom mast cell degranulating peptide. Biochim Biophys Acta. 1987;911(3):285–93. doi:10.1016/0167-4838(87)90069-0.
  31. Ziai MR, Russek S, Wang HC, Beer B, Blume AJ. Mast cell degranulating peptide: a multi-functional neurotoxin. J Pharm Pharmacol. 1990;42(7):457–61. doi:10.1111/j.2042-7158.1990.tb06595.x.
  32. Cherniack EP, Govorushko S. Bee venom acupuncture in humans. Toxicon. 2018;154:74–8. doi:10.1016/j.toxicon.2018.09.013.
  33. Havas LJ. Effect of bee venom on colchicine-induced tumours. Nature. 1950;166(4222):567–8. doi:10.1038/166567a0.
  34. de Graaf DC, Brochetto Braga MR, de Abreu, S Blank RMM, Bridts CH, De Clerck LS, et al. Standard methods for Apis mellifera venom research. J Apic Res. 2021;60(4):1–31. doi:10.1080/00218839.2020.1801073.
  35. Sengul F, Vatansev H, Ozturk B. Effects of bee venom and H-dental-derived mesenchymal stem cells on A549 cells. Mol Biol Rep. 2023;51(1):2. doi.org/10.1007/s11033-023-09002-2.
  36. Jeong YJ, Park YY, Park KK, Choi YH, Kim CH, Chang YC. Bee venom suppresses EGF-induced epithelial-mesenchymal transition and tumor invasion in lung cancer cells. Am J Chin Med. 2019;47(8):1869–83. doi:10.1142/S0192415X19500952.
  37. Choi KE, Hwang CJ, Gu SM, Park MH, Kim JH, Park JH, et al. Cancer cell growth inhibitory effect of bee venom via increase of death receptor 3 expression and inactivation of NF-kappa B in NSCLC cells. Toxins. 2014;6(8):2210–28. doi:10.3390/toxins6082210.
  38. Rady I, Siddiqui IA, Rady M, Mukhtar H. Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy. Cancer Lett. 2017;402:16–31. doi:10.1016/j.canlet.2017.05.010.
  39. Calabrese EJ. Biphasic dose responses in biology, toxicology and medicine: accounting for their generalizability and quantitative features. Environ Pollut. (Barking, Essex: 1987). 2013;182:452–60. doi:10.1016/j.envpol.2013.07.046.
  40. Nalbantsoy A, Varol E, Çaglar A, Yücel B. Cytotoxic and apoptotic effectiveness of Cypriot honeybee (Apis mellifera cypria) venom on various cancer cells. Turk J Biochem. 2024;49(3):446-54. doi:10.1515/tjb-2023-0109.
  41. Shi P, Xie S, Yang J, Zhang Y, Han S, Su S, Yao H. Pharmacological effects and mechanisms of bee venom and its main components: recent progress and perspective. Front Pharmacol. 2022;13:1001553. doi:10.3389/fphar.2022.1001553.