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In vitro cytotoxic activity of Tarantula cubensis alcoholic extract on different human cell lines

Year 2021, Volume: 42 Issue: 2, 252 - 259, 30.06.2021
https://doi.org/10.17776/csj.859132

Abstract

Spider venoms are known to have great potential for their antimicrobial, antifungal, and antitumor activities due to their rich peptide content. Tarantula cubensis alcoholic extract Theranekron® is a homeopathic remedy and it is frequently used in veterinary treatments. Specifically, the anti-inflammatory, antitumor and wound healing effects of Theranekron® provide a wide range of use in animal treatments. More importantly, it can reduce the growth rate of canine mammary tumors. This effect shows that Theranekron® can be a potential candidate for cancer treatment. In this study, the cytotoxic effect of Theranekron® was evaluated in four different human cancer cell lines and one non-cancerous human cell line. It was aimed to provide a foundation for further studies by conducting an in vitro screening for the cytotoxic effect of Theranekron®. Results showed that Theranekron® has a high cytotoxic effect on human breast cancer cell lines. On the other hand, the rate of cytotoxicity was found to be relatively lower on human small cell lung cancer, glioblastoma and human prostate cancer cell lines as compared to breast cancer cells. These results indicated that T. cubensis alcoholic extract might be utilized as an anticancer bio-therapeutic and should be further examined for its potential.

Thanks

The experiments in this paper were partially performed at Manisa Celal Bayar University (Turkey) - Applied Science and Research Center (DEFAM). Theranekron D6 solution used for the experiments was accessed courtesy of Veterinary Physician Bora Benli.

References

  • [1] King G. F., Venoms as a platform for human drugs: Translating toxins into therapeutics, Expert Opin. Biol. Ther., 11(11) (2011) 1469–1484.
  • [2] Oldrati V., Arrell M., Violette A., Perret F., Sprüngli X., Wolfender J. L., Stöcklin R., Advances in venomics, Mol. Biosyst., 12(12) (2016) 3530-3543.
  • [3] Lewis R.J., Garcia M.L., Therapeutic potential of venom peptides, Nat. Rev. Drug Discov., 2(10) (2003) 790-802
  • [4] Ilhan S., Çiçek K., Tok C.V., Atmaca H., Profiling of apoptosis-associated proteins in human prostate cancer cells in response to Montivipera bulgardaghica albizona venom by protein array, Toxin Rev., (2020) 1–8.
  • [5] Saez N. J., Senff, S., Jensen, J. E., Er, S.Y., Herzig, V., Rash, L.D., King, G.F., Spider-Venom Peptides as Therapeutics, Toxins (Basel), 2(12) (2010) 2851–2871.
  • [6] Comprehensive Cancer Information - National Cancer Institute, Available at: https://www.cancer.gov/. Retrieved Dec. 09, 2020.
  • [7] Pennington M. W., Czerwinski A., Norton R.S., Peptide therapeutics from venom: Current status and potential, Bioorganic Med. Chem., 26(10) (2018) 2738–2758.
  • [8] RichterPharma, Theranekron D6. Available at: https://www.richter-pharma.at/product-theranekron-d6_301.htm. https://www.richter-pharma.at/product-theranekron-d6_301.htm. RetrievedDec. 09, 2020.
  • [9] Ghasemi-Dizgah A., Nami B., Amirmozafari N., Tarantula cubensis venom (Theranekron®) selectively destroys human cancer cells via activating caspase-3-mediated apoptosis, Acta Medica Int., 4(1) (2017) 74-80.
  • [10] Kaçar C., Zonturlu A.K., Oral H., Yıldız S., Arı U.Ç., İneklerde erken puerperal dönemde theranekron uygulamalarının uterus involusyonu ve vaginal akıntı üzerine etkisi, Kafkas Üniversitesi Vet. Fak. Derg., 13(1) (2007) 11–15.
  • [11] Gültiken N., Rıfat Vural M., The effect of Tarantula cubensis extract applied in pre and postoperative period of canine mammary tumours, J. Istanbul Vet. Sci., 2(2) (2007) 13–23.
  • [12] Koch H., Stein M., Conservative and surgical treatment of panaritium (bovine interdigital necrobacillosis) of cattle in combination with Theranekron (spider venom preparation)., Prakt. Tierarzt, 61 (1980) 116–119.
  • [13] Sardari K., Kakhki E. G., Mohri M., Evaluation of wound contraction and epithelialization after subcutaneous administration of Theranekron® in cows, Comp. Clin. Path., 16(3) (2007) 197–200.
  • [14] Gül Satar N.Y., Cangül I.T., Topal A., Kurt H., Ipek V., Önel G.I., The effects of Tarantula cubensis venom on open wound healing in rats, J. Wound Care, 26(2) (2017) 66–71.
  • [15] Albay K., Şahi̇nduran Ş., Kale M., Karakurum Ç. M., Sezer, K., Influence of Tarantula cubensis Extract on the Treatment of the Oral Lesions in Cattle with Bluetongue Disease, Kafkas Univ. Vet.Fak.Derg., 16(4) (2021) 593–596.
  • [16] Lotfollahzadeh S., Alizadeh M.R., Mohri M., Mokhber Dezfouli M.R., The therapeutic effect of Tarentula cubensis extract (Theranekron®) in foot-and-mouth disease in cattle: A randomised trial in an endemic setting, Homeopathy, 101(3) (2012) 159–164.
  • [17] Paksoy Z., Güleşçi N., Kandemir F.M., Dinçel G.Ç., Effectiveness of levamisole and Tarantula cubensis extract in the treatment of teat Papillomatosis of cows, Indian J. Anim. Res., 49(5) (2015) 704–708.
  • [18] Karabacak M., Eraslan G., Kanbur M., Sarica Z.S., Effects of Tarantula cubensis D6 on aflatoxin-induced injury in biochemical parameters in rats, Homeopathy, 104(3) (2015) 205–210.
  • [19] Kızılay Z., Aktaş S., Kahraman Çetin N., Kılıç M.A., Özturk H., Effect of Tarantula cubensis extract (Theranekron) on peripheral nerve healing in an experimental sciatic nerve injury model in rats, Turk. Neurosurg., 29(5) (2019) 743–749.
  • [20] Er A., Çorum O., Çorum D.D., Hitit M., Dönmez H., Güzeloğlu A., Alcoholic extract of Tarantula cubensis induces apoptosis in MCF-7 cell line, Biomed. Res., 28(8) (2017) 3660–3665.
  • [21] Atmaca H., İlhan S., Batır M. B., Pulat Çamlı Ç., Güner A., Bektaş H., Novel benzimidazole derivatives: Synthesis, in vitro cytotoxicity, apoptosis and cell cycle studies, Chem. Biol. Interact., 327 (2020) 109163.
  • [22] de Souza-Fagundes E. M., Cota B. B., Almeida F. D. M., Anticancer Potential of Spider Venom, in Spider Venoms, Toxinology, (2016), 293–311.
  • [23] Gürbulak K., Akçay, A., Gümüşsoy, K.S., Sist, B., Steiner, S., Abay, M.,Canooğlu, E., Bekyürek, T., Investigation of the efficacy of Tarantula cubensis extract (Theranekron D6) in the treatment of subclinical and clinical mastitis in dairy cows, Turkish J. Vet. Anim. Sci., 38 (2014) 712–718.
  • [24] Içen H., Sekin S., Şimsek A., Kochan A., Tunik S., The efficacy of Tarantula cubensis extract (Theranekron) in treatment of canine oral papillomatosis, Asian J. Anim. Vet. Adv., 6(7) (2011) 744–749.
  • [25] Dolapçıoğlu K., Doğruer G., Özsoy Ş., Ergun Y., Çiftçi Ş., Soylu Karapınar O., Aslan E., Theranekron for treatment of endometriosis in a rat model compared with medroxyprogesterone acetate and leuprolide acetate, Eur. J. Obstet. Gynecol. Reprod. Biol., 170(1) (2013) 206–210.
  • [26] Oryan A., Moshiri A., Raayat A.R., Novel application of Theranekron® enhanced the structural and functional performance of the tenotomized tendon in rabbits, Cells Tiss. Org., 196(5) (2012) 442–455.
  • [27] Gültiken N., Güvenç, T., Kaya, D., Ağaoglu, A.R., Ay, S.S., Küçükaslan, I., Emre, B., Fındık, M., Schäfer-Somi, S., Aslan, S., Tarantula cubensis extract alters the degree of apoptosis and mitosis in canine mammary adenocarcinomas, J. Vet. Sci., 16(2) (2015) 213–219.
  • [28] Kumar R., Vadlamudi R.K., Adam L., Apoptosis in mammary gland and cancer, Endocr.-Relat. Cancer, 7(4) (2000) 257–269.
  • [29] Kumaraguruparan R., Prathiba D., Nagini S., Of humans and canines: Immunohistochemical analysis of PCNA, Bcl-2, p53, cytokeratin and ER in mammary tumours, Res. Vet. Sci., 81(2) (2006) 218–224.
  • [30] Rižner T. L., Estrogen metabolism and action in endometriosis, Mol. Cell. Endocrinol., 307(1-2) (2009) 8-18.
  • [31] Chantalat E., Valera, M. C., Vaysse, C., Noirrit, E., Rusidze, M., Weyl, A., Vergriete, K., Buscail, E., Lluel, P., Fontaine, C., Arnal, J. F., Lenfant, F., Estrogen receptors and endometriosis, Int. J. Mol. Sci., 21(8) (2020) 21082815.
  • [32] Brooks M. C., Locke E.R., Soule H.D., Estrogen Receptor in a Human Cell Line (MCF-7) from Breast, J. Biol. Chem., 248(10) (1973) 6251–6253.
  • [33] Gandhari M. K., Frazier C.R., Hartenstein J. S., Cloix J.F., Bernier M., Wainer I.W., Identification and characterization of estrogen receptor-related receptor alpha and gamma in human glioma and astrocytoma cells, Mol. Cell. Endocrinol., 315(1–2) (2010) 314–318.
  • [34] Hui A.M., Zhang, W., Chen, W., Xi, D., Purow, B., Friedman, G.C., Fine, H.A., Agents with selective estrogen receptor (ER) modulator activity induce apoptosis in vitro and in vivo in ER-negative glioma cells, Cancer Res., 64(24) (2004) 9115–9123.
  • .
Year 2021, Volume: 42 Issue: 2, 252 - 259, 30.06.2021
https://doi.org/10.17776/csj.859132

Abstract

References

  • [1] King G. F., Venoms as a platform for human drugs: Translating toxins into therapeutics, Expert Opin. Biol. Ther., 11(11) (2011) 1469–1484.
  • [2] Oldrati V., Arrell M., Violette A., Perret F., Sprüngli X., Wolfender J. L., Stöcklin R., Advances in venomics, Mol. Biosyst., 12(12) (2016) 3530-3543.
  • [3] Lewis R.J., Garcia M.L., Therapeutic potential of venom peptides, Nat. Rev. Drug Discov., 2(10) (2003) 790-802
  • [4] Ilhan S., Çiçek K., Tok C.V., Atmaca H., Profiling of apoptosis-associated proteins in human prostate cancer cells in response to Montivipera bulgardaghica albizona venom by protein array, Toxin Rev., (2020) 1–8.
  • [5] Saez N. J., Senff, S., Jensen, J. E., Er, S.Y., Herzig, V., Rash, L.D., King, G.F., Spider-Venom Peptides as Therapeutics, Toxins (Basel), 2(12) (2010) 2851–2871.
  • [6] Comprehensive Cancer Information - National Cancer Institute, Available at: https://www.cancer.gov/. Retrieved Dec. 09, 2020.
  • [7] Pennington M. W., Czerwinski A., Norton R.S., Peptide therapeutics from venom: Current status and potential, Bioorganic Med. Chem., 26(10) (2018) 2738–2758.
  • [8] RichterPharma, Theranekron D6. Available at: https://www.richter-pharma.at/product-theranekron-d6_301.htm. https://www.richter-pharma.at/product-theranekron-d6_301.htm. RetrievedDec. 09, 2020.
  • [9] Ghasemi-Dizgah A., Nami B., Amirmozafari N., Tarantula cubensis venom (Theranekron®) selectively destroys human cancer cells via activating caspase-3-mediated apoptosis, Acta Medica Int., 4(1) (2017) 74-80.
  • [10] Kaçar C., Zonturlu A.K., Oral H., Yıldız S., Arı U.Ç., İneklerde erken puerperal dönemde theranekron uygulamalarının uterus involusyonu ve vaginal akıntı üzerine etkisi, Kafkas Üniversitesi Vet. Fak. Derg., 13(1) (2007) 11–15.
  • [11] Gültiken N., Rıfat Vural M., The effect of Tarantula cubensis extract applied in pre and postoperative period of canine mammary tumours, J. Istanbul Vet. Sci., 2(2) (2007) 13–23.
  • [12] Koch H., Stein M., Conservative and surgical treatment of panaritium (bovine interdigital necrobacillosis) of cattle in combination with Theranekron (spider venom preparation)., Prakt. Tierarzt, 61 (1980) 116–119.
  • [13] Sardari K., Kakhki E. G., Mohri M., Evaluation of wound contraction and epithelialization after subcutaneous administration of Theranekron® in cows, Comp. Clin. Path., 16(3) (2007) 197–200.
  • [14] Gül Satar N.Y., Cangül I.T., Topal A., Kurt H., Ipek V., Önel G.I., The effects of Tarantula cubensis venom on open wound healing in rats, J. Wound Care, 26(2) (2017) 66–71.
  • [15] Albay K., Şahi̇nduran Ş., Kale M., Karakurum Ç. M., Sezer, K., Influence of Tarantula cubensis Extract on the Treatment of the Oral Lesions in Cattle with Bluetongue Disease, Kafkas Univ. Vet.Fak.Derg., 16(4) (2021) 593–596.
  • [16] Lotfollahzadeh S., Alizadeh M.R., Mohri M., Mokhber Dezfouli M.R., The therapeutic effect of Tarentula cubensis extract (Theranekron®) in foot-and-mouth disease in cattle: A randomised trial in an endemic setting, Homeopathy, 101(3) (2012) 159–164.
  • [17] Paksoy Z., Güleşçi N., Kandemir F.M., Dinçel G.Ç., Effectiveness of levamisole and Tarantula cubensis extract in the treatment of teat Papillomatosis of cows, Indian J. Anim. Res., 49(5) (2015) 704–708.
  • [18] Karabacak M., Eraslan G., Kanbur M., Sarica Z.S., Effects of Tarantula cubensis D6 on aflatoxin-induced injury in biochemical parameters in rats, Homeopathy, 104(3) (2015) 205–210.
  • [19] Kızılay Z., Aktaş S., Kahraman Çetin N., Kılıç M.A., Özturk H., Effect of Tarantula cubensis extract (Theranekron) on peripheral nerve healing in an experimental sciatic nerve injury model in rats, Turk. Neurosurg., 29(5) (2019) 743–749.
  • [20] Er A., Çorum O., Çorum D.D., Hitit M., Dönmez H., Güzeloğlu A., Alcoholic extract of Tarantula cubensis induces apoptosis in MCF-7 cell line, Biomed. Res., 28(8) (2017) 3660–3665.
  • [21] Atmaca H., İlhan S., Batır M. B., Pulat Çamlı Ç., Güner A., Bektaş H., Novel benzimidazole derivatives: Synthesis, in vitro cytotoxicity, apoptosis and cell cycle studies, Chem. Biol. Interact., 327 (2020) 109163.
  • [22] de Souza-Fagundes E. M., Cota B. B., Almeida F. D. M., Anticancer Potential of Spider Venom, in Spider Venoms, Toxinology, (2016), 293–311.
  • [23] Gürbulak K., Akçay, A., Gümüşsoy, K.S., Sist, B., Steiner, S., Abay, M.,Canooğlu, E., Bekyürek, T., Investigation of the efficacy of Tarantula cubensis extract (Theranekron D6) in the treatment of subclinical and clinical mastitis in dairy cows, Turkish J. Vet. Anim. Sci., 38 (2014) 712–718.
  • [24] Içen H., Sekin S., Şimsek A., Kochan A., Tunik S., The efficacy of Tarantula cubensis extract (Theranekron) in treatment of canine oral papillomatosis, Asian J. Anim. Vet. Adv., 6(7) (2011) 744–749.
  • [25] Dolapçıoğlu K., Doğruer G., Özsoy Ş., Ergun Y., Çiftçi Ş., Soylu Karapınar O., Aslan E., Theranekron for treatment of endometriosis in a rat model compared with medroxyprogesterone acetate and leuprolide acetate, Eur. J. Obstet. Gynecol. Reprod. Biol., 170(1) (2013) 206–210.
  • [26] Oryan A., Moshiri A., Raayat A.R., Novel application of Theranekron® enhanced the structural and functional performance of the tenotomized tendon in rabbits, Cells Tiss. Org., 196(5) (2012) 442–455.
  • [27] Gültiken N., Güvenç, T., Kaya, D., Ağaoglu, A.R., Ay, S.S., Küçükaslan, I., Emre, B., Fındık, M., Schäfer-Somi, S., Aslan, S., Tarantula cubensis extract alters the degree of apoptosis and mitosis in canine mammary adenocarcinomas, J. Vet. Sci., 16(2) (2015) 213–219.
  • [28] Kumar R., Vadlamudi R.K., Adam L., Apoptosis in mammary gland and cancer, Endocr.-Relat. Cancer, 7(4) (2000) 257–269.
  • [29] Kumaraguruparan R., Prathiba D., Nagini S., Of humans and canines: Immunohistochemical analysis of PCNA, Bcl-2, p53, cytokeratin and ER in mammary tumours, Res. Vet. Sci., 81(2) (2006) 218–224.
  • [30] Rižner T. L., Estrogen metabolism and action in endometriosis, Mol. Cell. Endocrinol., 307(1-2) (2009) 8-18.
  • [31] Chantalat E., Valera, M. C., Vaysse, C., Noirrit, E., Rusidze, M., Weyl, A., Vergriete, K., Buscail, E., Lluel, P., Fontaine, C., Arnal, J. F., Lenfant, F., Estrogen receptors and endometriosis, Int. J. Mol. Sci., 21(8) (2020) 21082815.
  • [32] Brooks M. C., Locke E.R., Soule H.D., Estrogen Receptor in a Human Cell Line (MCF-7) from Breast, J. Biol. Chem., 248(10) (1973) 6251–6253.
  • [33] Gandhari M. K., Frazier C.R., Hartenstein J. S., Cloix J.F., Bernier M., Wainer I.W., Identification and characterization of estrogen receptor-related receptor alpha and gamma in human glioma and astrocytoma cells, Mol. Cell. Endocrinol., 315(1–2) (2010) 314–318.
  • [34] Hui A.M., Zhang, W., Chen, W., Xi, D., Purow, B., Friedman, G.C., Fine, H.A., Agents with selective estrogen receptor (ER) modulator activity induce apoptosis in vitro and in vivo in ER-negative glioma cells, Cancer Res., 64(24) (2004) 9115–9123.
  • .
There are 36 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section Natural Sciences
Authors

Çisil Çamlı Pulat 0000-0002-9641-7219

Publication Date June 30, 2021
Submission Date January 12, 2021
Acceptance Date June 15, 2021
Published in Issue Year 2021Volume: 42 Issue: 2

Cite

APA Çamlı Pulat, Ç. (2021). In vitro cytotoxic activity of Tarantula cubensis alcoholic extract on different human cell lines. Cumhuriyet Science Journal, 42(2), 252-259. https://doi.org/10.17776/csj.859132