Research Article
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Arı zehiri bileşenlerinin akciğer kanserine karşı antikanser etkisi

Year 2024, Volume: 95 Issue: 1, 29 - 36, 15.01.2024
https://doi.org/10.33188/vetheder.1354383

Abstract

Bu çalışma ile arı zehrinin Calu-3 hücrelerinin proliferasyon kapasitesi ve hücrelerin migrasyonu yeteneği üzerindeki etkilerini belirlemeyi amaçlanmaktadır. Bu amaçla, Muğla ilinde yetiştirilen anadolu bal arısı (Apis mellifera anatolica) kolonilerinden arı zehri örnekleri toplanmıştır ve Calu-3 hücreleri bu arı zehirine maruz bırakılmıştır. Değişen dozlarda (20 μg/mL, 18 μg/mL, 15 μg/mL, 12 μg/mL, 10 μg/mL, 9 μg/mL, 7,5 μg/mL, 5 μg/mL, 2,5 μg/mL, 1,25 μg/mL, 0,625 μg/mL ve 0,312) arı zehri verilen Calu-3 kullanılarak hücre canlılığı testi gerçekleştirilmiştir. Çeşitli dozlarda (15 μg/mL, 10 μg/mL, 7,5 μg/mL, 1,25 μg/mL ve 0,312 μg/mL) arı zehrine maruz bırakılan Calu-3 hücrelerinde yara iyileştirme deneyi yapılmış ve hücreler 24 saat boyunca her iki saatte bir görüntülenmiştir. Çalışmamızın hücre proliferasyonu ve yara iyileşmesi deneyi sonuçlarına göre, arı zehirinin Calu-3 hücreleri üzerinde doza bağlı olarak değişebilen sitotoksik ve proliferatif etkisi olduğu görülmüştür. Çalışma, akciğer kanseri çalışmalarında arı zehrinin sitotoksik etkisinden dolayı kullanımında doz ayarlamasının ne kadar önemli olduğunu ortaya koymaktadır. Arı zehiri bileşenlerinin nasıl çalıştığını daha iyi anlamış olsak da arı zehirinin diğer maddelerle birleştirildiğinde Calu-3 hücrelerini nasıl etkilediğine bakılarak veya arı zehiri için saflaştırma yöntemi geliştirilerek arı zehri hakkında bilinenler geliştirilebilir.

References

  • Somwongin S, Chantawannakul P, Chaiyana W. Antioxidant activity and irritation property of venoms from Apis species. Toxicon 2018;145:32-39.
  • Bellik Y. Bee venom: its potential use in alternative medicine. Anti-infective agents 2015;13: 3-16.
  • Moreno M, Giralt E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: melittin, apamin and mastoparan. Toxins 2015;7:1126-1150.
  • 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 2019;24(16):2997-2298.
  • Hozzein WN, Badr G, Al Ghamdi AA, Sayed A, Al-Waili NS, Garraud O. Topical application of propolis enhances cutaneous wound healing by promoting TGF-beta/Smad-mediated collagen production in a streptozotocin-induced type I diabetic mouse model. Cellular Physiology and Biochemistry 2015;37(3):940-954.
  • Goharshenasan P, Amini S, Atria A, Abtahi H, Khorasani G. Topical application of honey on surgical wounds: A randomized clinical trial. Complementary Medicine Research 2016;23(1):12-15.
  • Oršolić, N. Bee venom in cancer therapy. Cancer and metastasis reviews 2012;31:173-194.
  • Khamis AA, Ali EM, Abd El-Moneim MA, Abd-Alhaseeb MM, El-Magd MA, Salim EI. Hesperidin, piperine and bee venom synergistically potentiate the anticancer effect of tamoxifen against breast cancer cells. Biomedicine & pharmacotherapy 2018;105:1335-1343.
  • Małek A, Strzemski M, Kurzepa J, Kurzepa J. Can Bee Venom Be Used as Anticancer Agent in Modern Medicine? Cancers 2023;15(14):3714.
  • Foster KA, Avery ML, Yazdanian M, Audus KL. Characterization of the Calu-3 cell line as a tool to screen pulmonary drug delivery. International journal of pharmaceutics 2000; 208(1-2):1-11.
  • Hutchinson BD, Shroff GS, Truong MT, Ko JP. Spectrum of lung adenocarcinoma. In Seminars in Ultrasound, CT and MRI 2019;40(3):255-264.
  • Denisenko TV, Budkevich IN, Zhivotovsky B. Cell death-based treatment of lung adenocarcinoma. Cell death & disease 2018;9(2):117.
  • Kreft ME, Jerman UD, Lasič E, Hevir-Kene N, Rižner TL, Peternel L, Kristan K. The characterization of the human cell line Calu-3 under different culture conditions and its use as an optimized in vitro model to investigate bronchial epithelial function. European Journal of Pharmaceutical Sciences 2015; 69:1-9.
  • DiGuilio KM, Rybakovsky E, Baek Y, Valenzano MC, Mullin JM. The multiphasic TNF-α-induced compromise of Calu-3 airway epithelial barrier function. Experimental Lung Research 2023;1-14.
  • Zhu Y, Chidekel A, Shaffer TH. Cultured human airway epithelial cells (calu-3): a model of human respiratory function, structure, and inflammatory responses. Critical care research and practice 2010;2010:1-8.
  • Liu CC, Hao DJ, Zhang Q, An J, Zhao JJ, Chen B, Yang, H. Application of bee venom and its main constituent melittin for cancer treatment. Cancer Chemother. Pharmacol 2016;78(6):1113-1130.
  • Gajski G, Garaj-Vrhovac V. Melittin: a lytic peptide with anticancer properties. Environ Toxicol Pharmacol 2013;36:697-705.
  • Jo M, Park MH, Kollipara PS, An BJ, Song HS, Han SB, Kim JH, Song MJ, Hong JT. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicol Appl Pharmacol 2012;258:72-81.
  • Jamasbi E, Batinovic S, Sharples RA, Sani MA, Robins- Browne RM, Wade JD, Separovic F, Hossain MA. Melittin peptides exhibit different activity on different cells and model membranes. Amino Acids 2014;46: 2759-2766.
  • Pandey P, Khan F, Khan MA, Kumar R, Upadhyay TK. An Updated Review Summarizing the Anticancer Efficacy of Melittin from Bee Venom in Several Models of Human Cancers. Nutrients 2023;15(14):3111.
  • Hwang YN, Kwon IS, Na HH, Park JS, Kim KC. Dual Cytotoxic Responses Induced by Treatment of A549 Human Lung Cancer Cells with Sweet Bee Venom in a Dose-Dependent Manner. Journal of Pharmacopuncture 2022;25(4):390.
  • Zhang SF, Chen Z. Melittin exerts an antitumor effect on non small cell lung cancer cells. Molecular medicine reports 2017;16(3):3581-3586.
  • Zhao J, Hu W, Zhang Z, Zhou Z, Duan J, Dong Z, Liu H, Yan C. Bee venom protects against pancreatic cancer via inducing cell cycle arrest and apoptosis with suppression of cell migration. J. Gastrointest Oncol 2022;13: 847–858.
  • Mansour GH, El-Magd MA, Mahfouz DH, Abdelhamid IA, Mohamed MF, Ibrahim NS, Hady AAbdel Wahab A, Elzayat EM. Bee venom and its active component Melittin synergistically potentiate the anticancer effect of Sorafenib against HepG2 cells. Bioorganic Chem 2021;116:105329.
  • Yaacoub C, Rifi M, El-Obeid D, Mawlawi H, Sabatier JM, Coutard B, Fajloun Z. 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;26:2264.
  • Li X, Zhu S, Li Z, Meng YQ, Huang SJ, Yu QY, Li B. Melittin induces ferroptosis and ER stress-CHOP-mediated apoptosis in A549 cells. Free Radical Research 2022;56(5-6):398-410.
  • Özgenç Ö, Sevin S. Wound healing effects of bee venom on adipose tissue derived mesenchymal stem cells. Veteriner Hekimler Derneği Dergisi 2023;94(1):59-66.
  • Yu JE, Kim Y, Hong DE, Lee DW, Chang JY, Yoo SS, Kim MJ, Son DJ, Yun J, Han SB. Bee Venom Triggers Autophagy-Induced Apoptosis in Human Lung Cancer Cells via the mTOR Signaling Pathway. J Oncol 2022; 2022:8916464.
  • Lee C, Bae SS, Joo H, Bae H. Melittin suppresses tumor progression by regulating tumor-associated macrophages in a Lewis lung carcinoma mouse model. Oncotarget 2017;8:54951–54965.
  • Kadasah SF, Alrefaei AF, Ali HA. Efficacy of Prunus armenica, Bee venom, and their combinations on p53 and Bcl-2 gene expression in human pancreatic and lung cancer cells. Journal of Umm Al-Qura University for Applied Sciences 2023:1-7.
  • Lee HL, Park SH, Kim TM, Jung YY, Park MH, Oh SH, Yun HS, Jun HO, Yoo HS, Han SB. Bee venom inhibits growth of human cervical tumors in mice. Oncotarget 2015;6:7280–7292.
  • Obeidat M, Al-Khraisat IF, Jaradat DMM, Ghanim BY, Abdallah QM, Arqoub DA, Sabbah D, Al-Sanabra OM, Arafat T, Qinna NA. Melittin peptide quantification in seasonally collected crude bee venom and its anticancer effects on myelogenous K562 human leukaemia cell line. BMC Complement Med Ther 2023;23: 132.
  • Borojeni SK, Zolfagharian H, Babaie M, Javadi I. Cytotoxic Effect of Bee (A. mellifera) Venom on Cancer Cell Lines. J. Pharma-copunct 2020;23:212–219.

Anticancer activity of bee venom components against lung cancer

Year 2024, Volume: 95 Issue: 1, 29 - 36, 15.01.2024
https://doi.org/10.33188/vetheder.1354383

Abstract

This study aims to determine the effects of bee venom on the proliferation capacity of Calu-3 cells and the migration ability of the cells. For this purpose, bee venom samples were collected from Apis mellifera anatoliaca in Muğla (Türkiye) provinces and Calu-3 cells were exposed to this bee venom. A test for cell viability using Calu-3 given bee venom in varied doses (20 μg/mL, 18 μg/mL, 15 μg/mL, 12 μg/mL, 10 μg/mL, 9 μg/mL, 7.5 μg/mL, 5 μg/mL, 2.5 μg/mL, 1.25 μg/mL, 0.625 μg/mL and 0.312 μg/mL) was conducted. And scratch assay was performed on cells treated with the doses (15 μg/mL, 10 μg/mL, 7.5 μg/mL, 1.25 and 0.312 μg/mL) and imaged every two hours for 24 hours. According to the results of our study's cell proliferation and scratch assays, bee venom had a cytotoxic and proliferative effect on Calu-3 cells which had a dose-dependent cytotoxic and proliferative effect. The study's outcomes how crucial dosage adjustment is in the use of bee venom in lung cancer studies due to its cytotoxic effect. Even though we have achieved a better understanding of how bee venom components work, our knowledge might still be improved by looking at how bee venom affects Calu-3 cells when combined with other substances or by developing the purification method for bee venom.

References

  • Somwongin S, Chantawannakul P, Chaiyana W. Antioxidant activity and irritation property of venoms from Apis species. Toxicon 2018;145:32-39.
  • Bellik Y. Bee venom: its potential use in alternative medicine. Anti-infective agents 2015;13: 3-16.
  • Moreno M, Giralt E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: melittin, apamin and mastoparan. Toxins 2015;7:1126-1150.
  • 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 2019;24(16):2997-2298.
  • Hozzein WN, Badr G, Al Ghamdi AA, Sayed A, Al-Waili NS, Garraud O. Topical application of propolis enhances cutaneous wound healing by promoting TGF-beta/Smad-mediated collagen production in a streptozotocin-induced type I diabetic mouse model. Cellular Physiology and Biochemistry 2015;37(3):940-954.
  • Goharshenasan P, Amini S, Atria A, Abtahi H, Khorasani G. Topical application of honey on surgical wounds: A randomized clinical trial. Complementary Medicine Research 2016;23(1):12-15.
  • Oršolić, N. Bee venom in cancer therapy. Cancer and metastasis reviews 2012;31:173-194.
  • Khamis AA, Ali EM, Abd El-Moneim MA, Abd-Alhaseeb MM, El-Magd MA, Salim EI. Hesperidin, piperine and bee venom synergistically potentiate the anticancer effect of tamoxifen against breast cancer cells. Biomedicine & pharmacotherapy 2018;105:1335-1343.
  • Małek A, Strzemski M, Kurzepa J, Kurzepa J. Can Bee Venom Be Used as Anticancer Agent in Modern Medicine? Cancers 2023;15(14):3714.
  • Foster KA, Avery ML, Yazdanian M, Audus KL. Characterization of the Calu-3 cell line as a tool to screen pulmonary drug delivery. International journal of pharmaceutics 2000; 208(1-2):1-11.
  • Hutchinson BD, Shroff GS, Truong MT, Ko JP. Spectrum of lung adenocarcinoma. In Seminars in Ultrasound, CT and MRI 2019;40(3):255-264.
  • Denisenko TV, Budkevich IN, Zhivotovsky B. Cell death-based treatment of lung adenocarcinoma. Cell death & disease 2018;9(2):117.
  • Kreft ME, Jerman UD, Lasič E, Hevir-Kene N, Rižner TL, Peternel L, Kristan K. The characterization of the human cell line Calu-3 under different culture conditions and its use as an optimized in vitro model to investigate bronchial epithelial function. European Journal of Pharmaceutical Sciences 2015; 69:1-9.
  • DiGuilio KM, Rybakovsky E, Baek Y, Valenzano MC, Mullin JM. The multiphasic TNF-α-induced compromise of Calu-3 airway epithelial barrier function. Experimental Lung Research 2023;1-14.
  • Zhu Y, Chidekel A, Shaffer TH. Cultured human airway epithelial cells (calu-3): a model of human respiratory function, structure, and inflammatory responses. Critical care research and practice 2010;2010:1-8.
  • Liu CC, Hao DJ, Zhang Q, An J, Zhao JJ, Chen B, Yang, H. Application of bee venom and its main constituent melittin for cancer treatment. Cancer Chemother. Pharmacol 2016;78(6):1113-1130.
  • Gajski G, Garaj-Vrhovac V. Melittin: a lytic peptide with anticancer properties. Environ Toxicol Pharmacol 2013;36:697-705.
  • Jo M, Park MH, Kollipara PS, An BJ, Song HS, Han SB, Kim JH, Song MJ, Hong JT. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicol Appl Pharmacol 2012;258:72-81.
  • Jamasbi E, Batinovic S, Sharples RA, Sani MA, Robins- Browne RM, Wade JD, Separovic F, Hossain MA. Melittin peptides exhibit different activity on different cells and model membranes. Amino Acids 2014;46: 2759-2766.
  • Pandey P, Khan F, Khan MA, Kumar R, Upadhyay TK. An Updated Review Summarizing the Anticancer Efficacy of Melittin from Bee Venom in Several Models of Human Cancers. Nutrients 2023;15(14):3111.
  • Hwang YN, Kwon IS, Na HH, Park JS, Kim KC. Dual Cytotoxic Responses Induced by Treatment of A549 Human Lung Cancer Cells with Sweet Bee Venom in a Dose-Dependent Manner. Journal of Pharmacopuncture 2022;25(4):390.
  • Zhang SF, Chen Z. Melittin exerts an antitumor effect on non small cell lung cancer cells. Molecular medicine reports 2017;16(3):3581-3586.
  • Zhao J, Hu W, Zhang Z, Zhou Z, Duan J, Dong Z, Liu H, Yan C. Bee venom protects against pancreatic cancer via inducing cell cycle arrest and apoptosis with suppression of cell migration. J. Gastrointest Oncol 2022;13: 847–858.
  • Mansour GH, El-Magd MA, Mahfouz DH, Abdelhamid IA, Mohamed MF, Ibrahim NS, Hady AAbdel Wahab A, Elzayat EM. Bee venom and its active component Melittin synergistically potentiate the anticancer effect of Sorafenib against HepG2 cells. Bioorganic Chem 2021;116:105329.
  • Yaacoub C, Rifi M, El-Obeid D, Mawlawi H, Sabatier JM, Coutard B, Fajloun Z. 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;26:2264.
  • Li X, Zhu S, Li Z, Meng YQ, Huang SJ, Yu QY, Li B. Melittin induces ferroptosis and ER stress-CHOP-mediated apoptosis in A549 cells. Free Radical Research 2022;56(5-6):398-410.
  • Özgenç Ö, Sevin S. Wound healing effects of bee venom on adipose tissue derived mesenchymal stem cells. Veteriner Hekimler Derneği Dergisi 2023;94(1):59-66.
  • Yu JE, Kim Y, Hong DE, Lee DW, Chang JY, Yoo SS, Kim MJ, Son DJ, Yun J, Han SB. Bee Venom Triggers Autophagy-Induced Apoptosis in Human Lung Cancer Cells via the mTOR Signaling Pathway. J Oncol 2022; 2022:8916464.
  • Lee C, Bae SS, Joo H, Bae H. Melittin suppresses tumor progression by regulating tumor-associated macrophages in a Lewis lung carcinoma mouse model. Oncotarget 2017;8:54951–54965.
  • Kadasah SF, Alrefaei AF, Ali HA. Efficacy of Prunus armenica, Bee venom, and their combinations on p53 and Bcl-2 gene expression in human pancreatic and lung cancer cells. Journal of Umm Al-Qura University for Applied Sciences 2023:1-7.
  • Lee HL, Park SH, Kim TM, Jung YY, Park MH, Oh SH, Yun HS, Jun HO, Yoo HS, Han SB. Bee venom inhibits growth of human cervical tumors in mice. Oncotarget 2015;6:7280–7292.
  • Obeidat M, Al-Khraisat IF, Jaradat DMM, Ghanim BY, Abdallah QM, Arqoub DA, Sabbah D, Al-Sanabra OM, Arafat T, Qinna NA. Melittin peptide quantification in seasonally collected crude bee venom and its anticancer effects on myelogenous K562 human leukaemia cell line. BMC Complement Med Ther 2023;23: 132.
  • Borojeni SK, Zolfagharian H, Babaie M, Javadi I. Cytotoxic Effect of Bee (A. mellifera) Venom on Cancer Cell Lines. J. Pharma-copunct 2020;23:212–219.
There are 33 citations in total.

Details

Primary Language English
Subjects Veterinary Histology and Embryology
Journal Section RESEARCH ARTICLE
Authors

Özge Özgenç Çınar 0000-0002-8776-4788

Early Pub Date January 12, 2024
Publication Date January 15, 2024
Submission Date September 2, 2023
Acceptance Date December 4, 2023
Published in Issue Year 2024 Volume: 95 Issue: 1

Cite

Vancouver Özgenç Çınar Ö. Anticancer activity of bee venom components against lung cancer. Vet Hekim Der Derg. 2024;95(1):29-36.

Veteriner Hekimler Derneği Dergisi (Journal of Turkish Veterinary Medical Society) is an open access publication, and the journal’s publication model is based on Budapest Access Initiative (BOAI) declaration. All published content is licensed under a Creative Commons CC BY-NC 4.0 license, available online and free of charge. Authors retain the copyright of their published work in Veteriner Hekimler Derneği Dergisi (Journal of Turkish Veterinary Medical Society). 

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