Bee Venom Toxic Effect on MDA-MB-231 Breast Cancer Cells and Caenorhabditis Elegans


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Abstract

Introduction:Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product.

Method:Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction.

Results:Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined.

Conclusion:Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.

About the authors

Yáskara Barros

Health Sciences Post-Graduate Program, Federal University of Sergipe

Email: info@benthamscience.net

Amanda de Andrade

Keizo Asami InstituKeizo Asami Institute, iLIKAte, Federal University of Pernambuco

Email: info@benthamscience.net

Larissa da Silva

ostgraduate Program in Biological Science, Federal University of Pernambuco

Email: info@benthamscience.net

Lucas Pedroza

Keizo Asami Institute, iLIKA,, Federal University of Pernambuco

Email: info@benthamscience.net

Iverson Bezerra

Keizo Asami Institute, iLIKA, Federal University of Pernambuco

Email: info@benthamscience.net

Iago Dillion Cavalcanti

Keizo Asami Institute, iLIKA,, Federal University of Pernambuco

Email: info@benthamscience.net

Mariane de Britto Lira Nogueira

Keizo Asami Institute, iLIKA, Federal University of Pernambuco

Email: info@benthamscience.net

Kristiana Mousinho

, CESMAC University Center

Email: info@benthamscience.net

Angelo Antoniolli

Department of Physiology, Federal University of Sergipe

Email: info@benthamscience.net

Luiz Alves

Keizo Asami Institute, iLIKA, Federal University of Pernambuco

Email: info@benthamscience.net

José de Lima Filho

Keizo Asami Institute, iLIKA,, Federal University of Pernambuco

Email: info@benthamscience.net

Alexandre Moura

MS4Life Laboratory of Mass Spectrometry, Health Sciences Postgraduate Program,, São Francisco University,

Email: info@benthamscience.net

Álex Rosini Silva

MS4Life Laboratory of Mass Spectrometry, Health Sciences Postgraduate Program,, São Francisco University

Email: info@benthamscience.net

Andréia de Melo Porcari

MS4Life Laboratory of Mass Spectrometry, Health Sciences Postgraduate Program, São Francisco University

Email: info@benthamscience.net

Priscila Gubert

Keizo Asami Institute, iLIKA, Federal University of Pernambuco

Author for correspondence.
Email: info@benthamscience.net

References

  1. Zolfagharian, H.; Mohajeri, M.; Babaie, M. Honey bee venom (apis mellifera) contains anticoagulation factors and increases the blood-clotting time. J. Pharmacopuncture, 2015, 18(4), 7-11. doi: 10.3831/KPI.2015.18.031 PMID: 26998384
  2. Aufschnaiter, A.; Kohler, V.; Khalifa, S.; Abd El-Wahed, A.; Du, M.; El-Seedi, H.; Büttner, S. Apitoxin and its components against cancer, neurodegeneration and rheumatoid arthritis: limitations and possibilities. Toxins, 2020, 12(2), 66. doi: 10.3390/toxins12020066 PMID: 31973181
  3. Hossen, M.S.; Gan, S.H.; Khalil, M.I. Melittin, a potential natural toxin of crude bee venom: Probable future arsenal in the treatment of diabetes mellitus. J. Chem., 2017, 2017, 1-7. doi: 10.1155/2017/4035626
  4. Leandro, L.F.; Mendes, C.A.; Casemiro, L.A. Antimicrobial activity of apitoxin, melittin and phospholipase A2 of honey bee (Apis mellifera) venom against oral pathogens. An Acad. Bras. Cienc., 2015, 87, 147-155.
  5. Jung, G.B.; Huh, J.E.; Lee, H.J.; Kim, D.; Lee, G.J.; Park, H.K.; Lee, J.D. Anti-cancer effect of bee venom on human MDA-MB-231 breast cancer cells using Raman spectroscopy. Biomed. Opt. Express, 2018, 9(11), 5703-5718. doi: 10.1364/BOE.9.005703 PMID: 30460157
  6. Lim, H.; Baek, S.; Jung, H. Bee venom and its peptide component melittin suppress growth and migration of melanoma cells via inhibition of PI3K/AKT/mTOR and MAPK pathways. Molecules, 2019, 24(5), 929. doi: 10.3390/molecules24050929 PMID: 30866426
  7. Zheng, J.; Lee, H.L.; Ham, Y.W.; Song, H.S.; Song, M.J.; Hong, J.T. Anti-cancer effect of bee venom on colon cancer cell growth by activation of death receptors and inhibition of nuclear factor kappa B. Oncotarget, 2015, 6(42), 44437-44451. doi: 10.18632/oncotarget.6295 PMID: 26561202
  8. Łukasiewicz, S.; Czeczelewski, M.; Forma, A.; Baj, J.; Sitarz, R.; Stanisławek, A. Breast cancer—epidemiology, risk factors, classification, prognostic markers, and current treatment strategies: An updated review. Cancers, 2021, 13(17), 4287. doi: 10.3390/cancers13174287 PMID: 34503097
  9. Dai, X.; Li, T.; Bai, Z.; Yang, Y.; Liu, X.; Zhan, J.; Shi, B. Breast cancer intrinsic subtype classification, clinical use and future trends. Am. J. Cancer Res., 2015, 5(10), 2929-2943. PMID: 26693050
  10. Martins, L.C.; Rezende, R.M.D.; Cordeiro, J.A.B.L.; Paula, H.S.C.; Bastos, D.R.; Costa, A.S.T.V.; Saddi, V.A.; Silva, A.M.T.C. Pattern of metastasis in triple negative breast cancer. Brazilian J. Mastol., 2017, 27(1), 8-14. doi: 10.5327/Z201700010003RBM
  11. Tavares, D.F.; Cardoso-Júnior, L.M.; Ribeiro, V.C.; Britto, R.L. The state of the art of immunotherapy in the treatment of triple-negative breast cancer: Main drugs, associations, mechanisms of action and future perspectives. Rev. Bras. Cancerol., 2021, 67(2), 061014. doi: 10.32635/2176-9745.RBC.2021v67n2.1014
  12. Daniluk, K.; Kutwin, M.; Grodzik, M.; Wierzbicki, M.; Strojny, B.; Szczepaniak, J.; Bałaban, J.; Sosnowska, M.; Chwalibog, A.; Sawosz, E.; Jaworski, S. Use of selected carbon nanoparticles as melittin carriers for MCF-7 and MDA-MB-231 human breast cancer cells. Materials, 2019, 13(1), 90. doi: 10.3390/ma13010090 PMID: 31878020
  13. Choi, D.I.; Kim, J.; Lee, H.; Kim, J.; Sung, Y.; Choi, J.E.; Venkat, S.J.; Park, P.; Jung, H.; Kaang, B.K. Synaptic correlates of associative fear memory in the lateral amygdala. Neuron, 2021, 109(17), 2717-2726.e3. doi: 10.1016/j.neuron.2021.07.003 PMID: 34363751
  14. Oršolić, N. Bee venom in cancer therapy. Cancer Metastasis Rev., 2012, 31(1-2), 173-194. doi: 10.1007/s10555-011-9339-3 PMID: 22109081
  15. Elieh Ali Komi, D.; Shafaghat, F.; Zwiener, R.D. Immunology of bee venom. Clin. Rev. Allergy Immunol., 2018, 54(3), 386-396. doi: 10.1007/s12016-017-8597-4 PMID: 28105558
  16. Ollert, M.; Blank, S. Anaphylaxis to insect venom allergens: Role of molecular diagnostics. Curr. Allergy Asthma Rep., 2015, 15(5), 26. doi: 10.1007/s11882-015-0527-z PMID: 26139335
  17. Hunt, P.R.; Camacho, J.A.; Sprando, R.L. Caenorhabditis elegans for predictive toxicology. Curr. Opin. Toxicol., 2020, 23-24, 23-28. doi: 10.1016/j.cotox.2020.02.004
  18. Huang, Z.; Ma, L.; Mishra, A.; Turnbull, J.E.; Tu, H. Editorial: C. elegans as an emerging model of pharmacological innovation. Front. Pharmacol., 2022, 13, 1029752. doi: 10.3389/fphar.2022.1029752 PMID: 36238559
  19. Markaki, M.; Tavernarakis, N. Caenorhabditis elegans as a model system for human diseases. Curr. Opin. Biotechnol., 2020, 63, 118-125. doi: 10.1016/j.copbio.2019.12.011 PMID: 31951916
  20. Zečić, A.; Braeckman, B.P. DAF-16/FoxO in caenorhabditis elegans and its role in metabolic remodeling. Cells, 2020, 9(1), 109. doi: 10.3390/cells9010109 PMID: 31906434
  21. Uno, M.; Tani, Y.; Nono, M.; Okabe, E.; Kishimoto, S.; Takahashi, C.; Abe, R.; Kurihara, T.; Nishida, E. Neuronal DAF-16-to-intestinal DAF-16 communication underlies organismal lifespan extension in C. elegans. iScience, 2021, 24(7), 102706. doi: 10.1016/j.isci.2021.102706 PMID: 34235410
  22. Back, P.; Braeckman, B.P.; Matthijssens, F. ROS in aging Caenorhabditis elegans: Damage or signaling? Oxid. Med. Cell. Longev., 2012, 2012, 1-14. doi: 10.1155/2012/608478 PMID: 22966416
  23. Hunt, P.R. The C. elegans model in toxicity testing. J. Appl. Toxicol., 2017, 37(1), 50-59. doi: 10.1002/jat.3357 PMID: 27443595
  24. Cavalcanti, I.D.L.; Ximenes, R.M.; Loiola Pessoa, O.D.; Santos Magalhães, N.S.; Lira-Nogueira, M.C.B. Fucoidan-coated PIBCA nanoparticles containing oncocalyxone A: Activity against metastatic breast cancer cells. J. Drug Deliv. Sci. Technol., 2021, 65, 102698. doi: 10.1016/j.jddst.2021.102698
  25. Lira, M.C.B.; Santos-Magalhães, N.S.; Nicolas, V.; Marsaud, V.; Silva, M.P.C.; Ponchel, G.; Vauthier, C. Cytotoxicity and cellular uptake of newly synthesized fucoidan-coated nanoparticles. Eur. J. Pharm. Biopharm., 2011, 79(1), 162-170. doi: 10.1016/j.ejpb.2011.02.013 PMID: 21349331
  26. Brenner, S. The genetics of Caenorhabditis elegans. Genetics, 1974, 77(1), 71-94. doi: 10.1093/genetics/77.1.71 PMID: 4366476
  27. Bischof, L.J.; Huffman, D.L.; Aroian, R.V. Assays for toxicity studies in <i&gt;C. elegans&lt;/i&gt; with Bt crystal proteins. In: C. elegans; Humana Press: New Jersey, 2006; pp. 139-154. doi: 10.1385/1-59745-151-7:139
  28. Wang, M.C.; O’Rourke, E.J.; Ruvkun, G. Fat metabolism links germline stem cells and longevity in C. elegans. Science, 2008, 322(1979), 957-960. doi: 10.1126/science.1162011
  29. Tsalik, E.L.; Hobert, O. Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans. J. Neurobiol., 2003, 56(2), 178-197. doi: 10.1002/neu.10245 PMID: 12838583
  30. Chalfie, M.; Sulston, J.E.; White, J.G.; Southgate, E.; Thomson, J.N.; Brenner, S. The neural circuit for touch sensitivity in Caenorhabditis elegans. J. Neurosci., 1985, 5(4), 956-964. doi: 10.1523/JNEUROSCI.05-04-00956.1985 PMID: 3981252
  31. Gubert, P.; Puntel, B.; Lehmen, T.; Bornhorst, J.; Avila, D.S.; Aschner, M.; Soares, F.A.A. Reversible reprotoxic effects of manganese through DAF-16 transcription factor activation and vitellogenin downregulation in Caenorhabditis elegans. Life Sci., 2016, 151, 218-223. doi: 10.1016/j.lfs.2016.03.016 PMID: 26972607
  32. Rangsinth, P.; Prasansuklab, A.; Duangjan, C.; Gu, X.; Meemon, K.; Wink, M.; Tencomnao, T. Leaf extract of Caesalpinia mimosoides enhances oxidative stress resistance and prolongs lifespan in Caenorhabditis elegans. BMC Complement. Altern. Med., 2019, 19(1), 164. doi: 10.1186/s12906-019-2578-5 PMID: 31286949
  33. Yin, J.; Hong, X.; Ma, L.; Liu, R.; Bu, Y. Non-targeted metabolomic profiling of atrazine in Caenorhabditis elegans using UHPLC-QE Orbitrap/MS. Ecotoxicol. Environ. Saf., 2020, 206, 111170. doi: 10.1016/j.ecoenv.2020.111170 PMID: 32861007
  34. Klupczynska, A.; Plewa, S.; Dereziński, P.; Garrett, T.J.; Rubio, V.Y.; Kokot, Z.J.; Matysiak, J. Identification and quantification of honeybee venom constituents by multiplatform metabolomics. Sci. Rep., 2020, 10(1), 21645. doi: 10.1038/s41598-020-78740-1 PMID: 33303913
  35. Azevedo, F.V.P.V.; Lopes, D.S.; Cirilo Gimenes, S.N.; Achê, D.C.; Vecchi, L.; Alves, P.T.; Guimarães, D.O.; Rodrigues, R.S.; Goulart, L.R.; Rodrigues, V.M.; Yoneyama, K.A.G. Human breast cancer cell death induced by BnSP-6, a Lys-49 PLA2 homologue from Bothrops pauloensis venom. Int. J. Biol. Macromol., 2016, 82, 671-677. doi: 10.1016/j.ijbiomac.2015.10.080 PMID: 26519876
  36. Bozorgi, A.; Khazaei, S.; Khademi, A.; Khazaei, M. Natural and herbal compounds targeting breast cancer, a review based on cancer stem cells. Iran. J. Basic Med. Sci., 2020, 23(8), 970-983. doi: 10.22038/ijbms.2020.43745.10270 PMID: 32952942
  37. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424. doi: 10.3322/caac.21492 PMID: 30207593
  38. Ip, S-W.; Liao, S-S.; Lin, S-Y.; Lin, J.P.; Yang, J.S.; Lin, M.L.; Chen, G.W.; Lu, H.F.; Lin, M.W.; Han, S.M.; Chung, J.G. The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. In Vivo, 2008, 22(2), 237-245. PMID: 18468409
  39. Duffy, C.; Sorolla, A.; Wang, E.; Golden, E.; Woodward, E.; Davern, K.; Ho, D.; Johnstone, E.; Pfleger, K.; Redfern, A.; Iyer, K.S.; Baer, B.; Blancafort, P. Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer. NPJ Precis. Oncol., 2020, 4(1), 24. doi: 10.1038/s41698-020-00129-0 PMID: 32923684
  40. Jeong, Y.J.; Choi, Y.; Shin, J.M.; Cho, H.J.; Kang, J.H.; Park, K.K.; Choe, J.Y.; Bae, Y.S.; Han, S.M.; Kim, C.H.; Chang, H.W.; Chang, Y.C. Melittin suppresses EGF-induced cell motility and invasion by inhibiting PI3K/Akt/mTOR signaling pathway in breast cancer cells. Food Chem. Toxicol., 2014, 68, 218-225. doi: 10.1016/j.fct.2014.03.022 PMID: 24675423
  41. Shiassi Arani, F.; Karimzadeh, L.; Ghafoori, S.M.; Nabiuni, M. Antimutagenic and synergistic cytotoxic effect of cisplatin and honey bee venom on 4t1 invasive mammary carcinoma cell line. Adv. Pharmacol. Sci., 2019, 2019, 1-8. doi: 10.1155/2019/7581318 PMID: 30838042
  42. Oršolić, N.; Šver, L.; Verstovšek, S.; Terzić, S.; Bašić, I. Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in vivo by bee venom. Toxicon, 2003, 41(7), 861-870. doi: 10.1016/S0041-0101(03)00045-X PMID: 12782086
  43. Oršolić, N.; Terzić, S.; Šver, L.; Bašić, I. Honey‐bee products in prevention and/or therapy of murine transplantable tumours. J. Sci. Food Agric., 2005, 85(3), 363-370. doi: 10.1002/jsfa.2041
  44. Ahn, Y.; Shin, J.S.; Lee, J.; Lee, Y.J.; Kim, M.; Shin, Y.; Park, K.B.; Kim, E.J.; Kim, M.J.; Lee, J.; Lee, H.D.; Lee, Y.; Kim, S.; Chung, H.J.; Ha, I.H. Safety of essential bee venom pharmacopuncture as assessed in a randomized controlled double-blind trial. J. Ethnopharmacol., 2016, 194, 774-780. doi: 10.1016/j.jep.2016.11.012 PMID: 27840257
  45. Cherniack, E.P.; Govorushko, S. To bee or not to bee: The potential efficacy and safety of bee venom acupuncture in humans. Toxicon, 2018, 154, 74-78. doi: 10.1016/j.toxicon.2018.09.013 PMID: 30268393
  46. DeGrado, W.F.; Musso, G.F.; Lieber, M.; Kaiser, E.T.; Kézdy, F.J. Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue. Biophys. J., 1982, 37(1), 329-338. doi: 10.1016/S0006-3495(82)84681-X PMID: 7055625
  47. Pan, H.; Soman, N.R.; Schlesinger, P.H.; Lanza, G.M.; Wickline, S.A. Cytolytic peptide nanoparticles (‘NanoBees’) for cancer therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2011, 3(3), 318-327. doi: 10.1002/wnan.126 PMID: 21225660
  48. Peeler, D.J.; Thai, S.N.; Cheng, Y.; Horner, P.J.; Sellers, D.L.; Pun, S.H. pH-sensitive polymer micelles provide selective and potentiated lytic capacity to venom peptides for effective intracellular delivery. Biomaterials, 2019, 192, 235-244. doi: 10.1016/j.biomaterials.2018.11.004 PMID: 30458359
  49. Xing, L.; Dawei, C.; Liping, X.; Rongqing, Z. Oral colon-specific drug delivery for bee venom peptide: Development of a coated calcium alginate gel beads-entrapped liposome. J. Control. Release, 2003, 93(3), 293-300. doi: 10.1016/j.jconrel.2003.08.019 PMID: 14644579
  50. Das, B.; Madhubala, D.; Mahanta, S.; Patra, A.; Puzari, U.; Khan, M.R.; Mukherjee, A.K. A novel therapeutic formulation for the improved treatment of indian red scorpion (mesobuthus tamulus) venom-induced toxicity-tested in caenorhabditis elegans and rodent models. Toxins, 2023, 15(8), 504. doi: 10.3390/toxins15080504 PMID: 37624261
  51. Kaletta, T.; Hengartner, M.O. Finding function in novel targets: C. elegans as a model organism. Nat. Rev. Drug Discov., 2006, 5(5), 387-399. doi: 10.1038/nrd2031 PMID: 16672925
  52. Boyd, W.A.; Smith, M.V.; Co, C.A.; Pirone, J.R.; Rice, J.R.; Shockley, K.R.; Freedman, J.H. Developmental effects of the toxcastTM phase i and phase ii chemicals in Caenorhabditis elegans and corresponding responses in zebrafish, rats, and rabbits. Environ. Health Perspect., 2016, 124(5), 586-593. doi: 10.1289/ehp.1409645 PMID: 26496690
  53. Chattopadhyay, D.; Thirumurugan, K. Longevity promoting efficacies of different plant extracts in lower model organisms. Mech. Ageing Dev., 2018, 171, 47-57. doi: 10.1016/j.mad.2018.03.002 PMID: 29526449
  54. da Silveira, T.L.; Zamberlan, D.C.; Arantes, L.P.; Machado, M.L.; da Silva, T.C.; Câmara, D.F.; Santamaría, A.; Aschner, M.; Soares, F.A.A. Quinolinic acid and glutamatergic neurodegeneration in Caenorhabditis elegans. Neurotoxicology, 2018, 67, 94-101. doi: 10.1016/j.neuro.2018.04.015 PMID: 29702159
  55. Zečić, A.; Dhondt, I.; Braeckman, B.P. The nutritional requirements of Caenorhabditis elegans. Genes Nutr., 2019, 14(1), 15. doi: 10.1186/s12263-019-0637-7 PMID: 31080524
  56. Branicky, R.; Hekimi, S. What keeps C. elegans regular: The genetics of defecation. Trends Genet., 2006, 22(10), 571-579. doi: 10.1016/j.tig.2006.08.006 PMID: 16911844
  57. Gonzalez-Moragas, L.; Roig, A.; Laromaine, A.C. elegans as a tool for in vivo nanoparticle assessment. Adv. Colloid Interface Sci., 2015, 219, 10-26. doi: 10.1016/j.cis.2015.02.001 PMID: 25772622
  58. Treinin, M.; Jin, Y. Cholinergic transmission in C. elegans: Functions, diversity, and maturation of ACh‐activated ion channels. J. Neurochem., 2021, 158(6), 1274-1291. doi: 10.1111/jnc.15164 PMID: 32869293
  59. Mitchell, H.K.; Lowy, P.H.; Sarmiento, L.; Dickson, L. Melittin: Toxicity to Drosophila and inhibition of acetylcholinesterase. Arch. Biochem. Biophys., 1971, 145(1), 344-348. doi: 10.1016/0003-9861(71)90045-2 PMID: 5001227
  60. Philippsen, D.F.; Tamagno, W.A.; Vanin, A.P.; Concato, A.C.; Bragagnolo, L.; Prestes, E.; Korf, E.P.; Kaizer, R.R. Copper uses in organic production are safe to the nervous system of Caenorhabditis elegans? Environ. Qual. Manage., 2021, 30(4), 61-70. doi: 10.1002/tqem.21736
  61. Anderson, G.L.; Cole, R.D.; Williams, P.L. Assessing behavioral toxicity with Caenorhabditis elegans. Environ. Toxicol. Chem., 2004, 23(5), 1235-1240. doi: 10.1897/03-264 PMID: 15180374
  62. Mansur, F.; Luoga, W.; Buttle, D.J.; Duce, I.R.; Lowe, A.; Behnke, J.M. The anthelmintic efficacy of natural plant cysteine proteinases against two rodent cestodes Hymenolepis diminuta and Hymenolepis microstomain vitro. Vet. Parasitol., 2014, 201(1-2), 48-58. doi: 10.1016/j.vetpar.2013.12.018 PMID: 24462509
  63. Williams, A.R.; Fryganas, C.; Ramsay, A.; Mueller-Harvey, I.; Thamsborg, S.M. Direct anthelmintic effects of condensed tannins from diverse plant sources against Ascaris suum. PLoS One, 2014, 9(5), e97053. doi: 10.1371/journal.pone.0097053 PMID: 24810761
  64. Rehman, A.; Ullah, R.; Jaiswal, N.; Khan, M.A.H.; Rehman, L.; Beg, M.A.; Malhotra, S.K.; Abidi, S.M.A. Low virulence potential and in vivo transformation ability in the honey bee venom treated Clinostomum Complanatum. Exp. Parasitol., 2017, 183, 33-40. doi: 10.1016/j.exppara.2017.10.007 PMID: 29069571
  65. Hashmi, S.; Zhang, J.; Oksov, Y.; Ji, Q.; Lustigman, S. The Caenorhabditis elegans CPI-2a cystatin-like inhibitor has an essential regulatory role during oogenesis and fertilization. J. Biol. Chem., 2006, 281(38), 28415-28429. doi: 10.1074/jbc.M600254200 PMID: 16857685
  66. Jang, S.H.; Park, Y.; Park, S.C.; Il Kim, P.; Lee, D.G.; Hahm, K.S. Antinematodal activity and the mechanism of the antimicrobial peptide, HP (2-20), against Caenorhabditis elegans. Biotechnol. Lett., 2004, 26(4), 287-291. doi: 10.1023/B:BILE.0000015427.26410.d4 PMID: 15055763
  67. DiLoreto, R.; Murphy, C.T. The cell biology of aging. Mol. Biol. Cell, 2015, 26(25), 4524-4531. doi: 10.1091/mbc.E14-06-1084 PMID: 26668170
  68. Kenyon, C. A pathway that links reproductive status to lifespan in Caenorhabditis elegans. Ann. N. Y. Acad. Sci., 2010, 1204(1), 156-162. doi: 10.1111/j.1749-6632.2010.05640.x PMID: 20738286
  69. Dues, D.J.; Andrews, E.K.; Schaar, C.E.; Bergsma, A.L.; Senchuk, M.M.; Van Raamsdonk, J.M. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways. Aging, 2016, 8(4), 777-795. doi: 10.18632/aging.100939 PMID: 27053445
  70. Henderson, S.T.; Johnson, T.E. daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr. Biol., 2001, 11(24), 1975-1980. doi: 10.1016/S0960-9822(01)00594-2 PMID: 11747825
  71. Farhan, M.; Silva, M.; Xingan, X.; Huang, Y.; Zheng, W. Role of FOXO transcription factors in cancer metabolism and angiogenesis. Cells, 2020, 9(7), 1586. doi: 10.3390/cells9071586 PMID: 32629884
  72. Wan, Q.L.; Shi, X.; Liu, J.; Ding, A.J.; Pu, Y.Z.; Li, Z.; Wu, G.S.; Luo, H.R. Metabolomic signature associated with reproduction-regulated aging in Caenorhabditis elegans. Aging, 2017, 9(2), 447-474. doi: 10.18632/aging.101170 PMID: 28177875
  73. Lemieux, G.A.; Ashrafi, K. Investigating connections between metabolism, longevity, and behavior in Caenorhabditis elegans. Trends Endocrinol. Metab., 2016, 27(8), 586-596. doi: 10.1016/j.tem.2016.05.004 PMID: 27289335
  74. Utkin, Y.N. Animal venom studies: Current benefits and future developments. World J. Biol. Chem., 2015, 6(2), 28-33. doi: 10.4331/wjbc.v6.i2.28 PMID: 26009701
  75. Nelson, D.A.; O’Connor, R. The venom of the honeybee (Apis mellifera): Free amino acids and peptides. Can. J. Biochem., 1968, 46(10), 1221-1226. doi: 10.1139/o68-182 PMID: 5687646
  76. Surendra, N.S.; Ravikumar, H.; Reddy, M.R.S. Evaluation of catecholamines and amino acids from venom reservoir extract of Indian honey bee (Apis) species. J. Apic. Res., 2014, 53(5), 514-519. doi: 10.3896/IBRA.1.53.5.05
  77. Popplewell, J.F.; Swann, M.J.; Freeman, N.J.; McDonnell, C.; Ford, R.C. Quantifying the effects of melittin on liposomes. Biochim. Biophys. Acta Biomembr., 2007, 1768(1), 13-20. doi: 10.1016/j.bbamem.2006.05.016 PMID: 17092481
  78. Molenaars, M.; Schomakers, B.V.; Elfrink, H.L.; Gao, A.W.; Vervaart, M.A.T.; Pras-Raves, M.L.; Luyf, A.C.; Smith, R.L.; Sterken, M.G.; Kammenga, J.E.; van Kampen, A.H.C.; Janssens, G.E.; Vaz, F.M.; van Weeghel, M.; Houtkooper, R.H. Metabolomics and lipidomics in Caenorhabditis elegans using a single-sample preparation. Dis. Model. Mech., 2021, 14(4), dmm047746. doi: 10.1242/dmm.047746 PMID: 33653825
  79. Jin, J.; Byun, J.K.; Choi, Y.K.; Park, K.G. Targeting glutamine metabolism as a therapeutic strategy for cancer. Exp. Mol. Med., 2023, 55(4), 706-715. doi: 10.1038/s12276-023-00971-9 PMID: 37009798
  80. Butler, M.; van der Meer, L.T.; van Leeuwen, F.N. Amino acid depletion therapies: Starving cancer cells to death. Trends Endocrinol. Metab., 2021, 32(6), 367-381. doi: 10.1016/j.tem.2021.03.003 PMID: 33795176
  81. Dallière, N.; Bhatla, N.; Luedtke, Z.; Ma, D.K.; Woolman, J.; Walker, R.J.; Holden-Dye, L.; O’Connor, V. Multiple excitatory and inhibitory neural signals converge to fine‐tune Caenorhabditis elegans feeding to food availability. FASEB J., 2016, 30(2), 836-848. doi: 10.1096/fj.15-279257 PMID: 26514165
  82. Lieu, E.L.; Nguyen, T.; Rhyne, S.; Kim, J. Amino acids in cancer. Exp. Mol. Med., 2020, 52(1), 15-30. doi: 10.1038/s12276-020-0375-3 PMID: 31980738
  83. Eren, C.Y.; Gurer, H.G.; Gursoy, O.O.; Sezer, C.V. Antitumor effects of l-citrulline on hela cervical cancer cell lines. Anticancer. Agents Med. Chem., 2022, 22(18), 3157-3162. doi: 10.2174/1871520622666220426101409 PMID: 35473537
  84. Corsetto, P.A.; Zava, S.; Rizzo, A.M.; Colombo, I. The critical impact of sphingolipid metabolism in breast cancer progression and drug response. Int. J. Mol. Sci., 2023, 24(3), 2107. doi: 10.3390/ijms24032107 PMID: 36768427
  85. Nagahashi, M.; Tsuchida, J.; Moro, K.; Hasegawa, M.; Tatsuda, K.; Woelfel, I.A.; Takabe, K.; Wakai, T. High levels of sphingolipids in human breast cancer. J. Surg. Res., 2016, 204(2), 435-444. doi: 10.1016/j.jss.2016.05.022 PMID: 27565080
  86. Li, Y.; Kong, D.; Fu, Y.; Sussman, M.R.; Wu, H. The effect of developmental and environmental factors on secondary metabolites in medicinal plants. Plant Physiol. Biochem., 2020, 148, 80-89. doi: 10.1016/j.plaphy.2020.01.006 PMID: 31951944
  87. Barfeld, S.J.; Fazli, L.; Persson, M.; Marjavaara, L.; Urbanucci, A.; Kaukoniemi, K.M.; Rennie, P.S.; Ceder, Y.; Chabes, A.; Visakorpi, T.; Mills, I.G. Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer. Oncotarget, 2015, 6(14), 12587-12602. doi: 10.18632/oncotarget.3494 PMID: 25869206

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