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Cytotoxic Effects of Theranekron D6 on HepG2 Heaptocellular Carcinoma Cells

Yıl 2024, Cilt: 45 Sayı: 1, 8 - 14, 28.03.2024

Deniz Şumnulu

https://doi.org/10.17776/csj.1363685

Öz

Theranekron D6 is an alcholic extract of Tarantul cubensis. In this study, the cytotoxic effects of Theranekron D6 on HepG2 and on AML12 cells were investigated by MTT analyses. Gene expression analyses were performed by qRT-PCR. Apoptotic, necrotic, and healthy cells were viewed by a fluorescent microscope, and they were counted by a flow cytometry device. 143 µg/mL Theranekron D6 was calculated as an IC50 value for HepG2 cells, and it was applied to both cell lines. No significant increase in the amount of apoptotic and necrotic cells was observed at the AML12 cells, while both of them increased by 31.04% at the HepG2 cells by Therankron D6 application. The accuracy of flow cytometry data was confirmed through fluorescence microscope analyses. At the HepG2 cells, significant increases were observed at the expression levels of Bax (5.61 ± 0.34), Cas3 (2.74 ± 0.34), APAF1 (3.64 ± 0.44), and p53 (2.10 ± 0.3) genes, but at the AML12 cells, the expression levels of the same genes 1.14 ± 0.14, 0.54 ± 0.17, 0.71 ± 0.17, and 0.93 ± 0.3 not increased. Based on these data, it was concluded that Theranekron D6 may be a chemotherapy candidate for HepG2 cells.

Anahtar Kelimeler

AML12 Anticancer Cytotoxicity HepG2 Tarantula cubensis D6.

Kaynakça

  • [1] Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F., Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012, Int J Cancer, 136(5) (2015) E359–86.
  • [2] Torre L., Global cancer statistics, 2012, CA-CANCER J CLIN, 65(2) (2015) 87–108.
  • [3] Park J.W., Chen M., Colombo M., Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study, LIVER INT, 35(9) (2015) 2155- 2166.
  • [4] EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma, J Hepatol., 56(4) (2012) 908–43.
  • [5] Laursen L., A preventable cancer, Nature, 516(7529) (2014) S2– 3.
  • [6] McGlynn KA, London W.T., “The global epidemiology of hepatocellular carcinoma: present and future”, Clin Liver Dis., 15(2) (2011) 223–x.
  • [7] McGlynn K.A., Petrick J.L., London W.T., “Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability”, Clin Liver Dis., 19(2) (2015) 223– 38.
  • [8] Sim H.W., Knox J., Hepatocellular carcinoma in the era of immunotherapy, Curr Probl Cancer, 42(1) (2018) 40– 48.
  • [9] Gomes A., Bhattacharjee P., Mishra R., Biswas A.K., Dasgupta S.C., Giri B., Anticancer potential of animal venoms and toxins, Indian J Exp Biol., 48(2) (2010) 93-103.
  • [10] Chang N.S., Transforming growth factor-beta protection of cancer cells against tumor necrosis factor cytotoxicity is counteracted by hyaluronidase (review), Int J Mol Med, 2(6) (1998) 653-9.
  • [11] Zargan J., Sajad M., Umar S., Naime M., Ali S., Khan H.A., Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells, Mol Cell Biochem., 348(1-2) (2011) 173-81.
  • [12] Caliskan F., García B.I., Coronas F.I., Batista C.V., Zamudio F.Z., Possani L.D., Characterization of venom components from the scorpion Androctonus crassicauda of Turkey: peptides and genes, Toxicon, 48(1) (2006) 12-22.
  • [13] D'Suze G., Rosales A., Salazar V., Sevcik C., Apoptogenic peptides from Tityus discrepans scorpion venom acting against the SKBR3 breast cancer cell line, Toxicon, 56(8) (2010) 1497-505.
  • [14] Li H.M., Wang D.C., Zeng Z.H., Jin L., Hu R.Q., Crystal structure of an acidic neurotoxin from scorpion Buthus martensii Karsch at 1.85 Å resolution, J Mol Biol., 261(3) (1996) 415-31.
  • [15] Oliveira E.B., Farias K.J.S., Gomes D.L., de Araújo J.M.G., da Silva W.D., Rocha H.A.O., Donadi E.A., Fernandes-Pedrosa M.F., Crispim J.C.O., Tityus serrulatus Scorpion Venom Induces Apoptosis in Cervical Cancer Cell Lines. Evid Based Complement Alternat Med., 2019: 5131042.
  • [16] Fu Y.J., Yin L.T., Liang A.H., Zhang C.F., Wang W., Chai B.F., Fan X.J., Therapeutic potential of chlorotoxin-like neurotoxin from the Chinese scorpion for humangliomas, Neurosci Lett., 412(1) (2007) 62-7.
  • [17] Mamelak A.N., Jacoby D.B., Targeted Delivery of Antitumoral Therapy to Glioma and Other Malignancies with Synthetic Chlorotoxin (TM-601), Expert Opin Drug Deliv., 4(2) (2007) 175-86.
  • [18] Stampa S., A field trial comparing the efficacy of sulphamonomethoxine, penicillin, and tarantula poison in the treatment of pododermatitis circumspecta of cattle, J S Afr Vet Assoc., 57(2) (1986) 91–3.
  • [19] Cam Y., Kibar M., Atasever A., Atalay O., Beyaz L., Efficacy of levamisole and Tarantula cubensis venom for the treatment of bovine cutaneous papillomatosis, Vet Rec., 160(14) (2007) 486–8.
  • [20] Icen H., Sekin S., Simsek 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.
  • [21] Paksoy Z., Gülesci 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) 704–8.
  • [22] Sardari K., Kakhki E.G., Mohri M., Evaluation of wound contraction and epithelialization after subcutaneous administration of TheranekronR in cows, Comp Clin Path., 16(3) (2007) 197–200.
  • [23] Gultiken N., Guvenc T., Kaya D., Agaoglu A.R., Ay S.S., Kucukaslan I., Emre B., Findik M., Schafer-Somi S., Aslan S., Tarantula cubensis extract alters the degree of apoptosis and mitosis in canine mammary adenocarcinomas, J Vet Sci., 16(2) (2015) 213–9.
  • [24] Al-Asmari A.K., Riyasdeen A., Al-Shahrani M.H., Islam M., Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines, Onco Targets Ther., 15 (2022) 1289.
  • [25] Akhtar B., Muhammad F., Sharif A., Anwar M.I., Mechanistic insights of snake venom disintegrins in cancer treatment, Eur J Pharmacol., 899 (2021) 174022.
  • [26] Chong H.P., Tan K.Y., Tan C.H., Cytotoxicity of snake venoms and cytotoxins from two southeast Asian cobras (Naja sumatrana, Naja kaouthia): exploration of anticancer potential, selectivity, and cell death mechanism, Front Mol Biosci., 7 (2020) 583587.
  • [27] Orrenius S., Gogvadze V., Zhivotovsky B., Mitochondrial Oxidative Stress: Implications for Cell Death, Annu Rev Pharmacol Toxicol., 47 (2007) 143-183.
  • [28] Yokoyama C., Sueyoshi Y., Ema M., Mori Y., Takaishi K., Hisatomi H., Induction of oxidative stress by anticancer drugs in the presence and absence of cells, Oncol Lett., 14(5) (2017) 6066-70.
  • [29] Çamlı Pulat Ç., In vitro cytotoxic activity of Tarantula cubensis alcoholic extract on different human cell lines. Cumhuriyet Sci. J., 42(2) (2021) 252-259.
  • [30] Ilhan S., Can a Veterinary Drug be Repurposed for Human Cancers?: Cytotoxic Effect of Tarantula cubensis Venom on Human Cancer Cells. Journal of the Institute of Science and Technology, 11(3) (2021) 1763-1769.
  • [31] Andreyev A.Y., Kushnareva Y.E., Starkov A.A., Mitochondrial metabolism of reactive oxygen species, Biochemistry, 70 (2005) 200–214.
  • [32] Vermes I., Haanen C., Steffens-Nakken H., Reutelingsperger C., A novel assay for apoptosis Flow cytometric detection of phosphatidylserine early apoptotic cells using fluorescein labelled expression on Annexin V. Journal of Immunological Methods, 184 (1995) 39-51
  • [33] Dasari M., Acharya A.P., Kim D., Lee S., Lee S., Rhea J., Molinaro R., Murthy N., H-gemcitabine: A new gemcitabine prodrug for treating cancer, Bioconjugate Chem., 24 (2013) 4–8.

Yıl 2024, Cilt: 45 Sayı: 1, 8 - 14, 28.03.2024

Deniz Şumnulu

https://doi.org/10.17776/csj.1363685

Öz

Kaynakça

  • [1] Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F., Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012, Int J Cancer, 136(5) (2015) E359–86.
  • [2] Torre L., Global cancer statistics, 2012, CA-CANCER J CLIN, 65(2) (2015) 87–108.
  • [3] Park J.W., Chen M., Colombo M., Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study, LIVER INT, 35(9) (2015) 2155- 2166.
  • [4] EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma, J Hepatol., 56(4) (2012) 908–43.
  • [5] Laursen L., A preventable cancer, Nature, 516(7529) (2014) S2– 3.
  • [6] McGlynn KA, London W.T., “The global epidemiology of hepatocellular carcinoma: present and future”, Clin Liver Dis., 15(2) (2011) 223–x.
  • [7] McGlynn K.A., Petrick J.L., London W.T., “Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability”, Clin Liver Dis., 19(2) (2015) 223– 38.
  • [8] Sim H.W., Knox J., Hepatocellular carcinoma in the era of immunotherapy, Curr Probl Cancer, 42(1) (2018) 40– 48.
  • [9] Gomes A., Bhattacharjee P., Mishra R., Biswas A.K., Dasgupta S.C., Giri B., Anticancer potential of animal venoms and toxins, Indian J Exp Biol., 48(2) (2010) 93-103.
  • [10] Chang N.S., Transforming growth factor-beta protection of cancer cells against tumor necrosis factor cytotoxicity is counteracted by hyaluronidase (review), Int J Mol Med, 2(6) (1998) 653-9.
  • [11] Zargan J., Sajad M., Umar S., Naime M., Ali S., Khan H.A., Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells, Mol Cell Biochem., 348(1-2) (2011) 173-81.
  • [12] Caliskan F., García B.I., Coronas F.I., Batista C.V., Zamudio F.Z., Possani L.D., Characterization of venom components from the scorpion Androctonus crassicauda of Turkey: peptides and genes, Toxicon, 48(1) (2006) 12-22.
  • [13] D'Suze G., Rosales A., Salazar V., Sevcik C., Apoptogenic peptides from Tityus discrepans scorpion venom acting against the SKBR3 breast cancer cell line, Toxicon, 56(8) (2010) 1497-505.
  • [14] Li H.M., Wang D.C., Zeng Z.H., Jin L., Hu R.Q., Crystal structure of an acidic neurotoxin from scorpion Buthus martensii Karsch at 1.85 Å resolution, J Mol Biol., 261(3) (1996) 415-31.
  • [15] Oliveira E.B., Farias K.J.S., Gomes D.L., de Araújo J.M.G., da Silva W.D., Rocha H.A.O., Donadi E.A., Fernandes-Pedrosa M.F., Crispim J.C.O., Tityus serrulatus Scorpion Venom Induces Apoptosis in Cervical Cancer Cell Lines. Evid Based Complement Alternat Med., 2019: 5131042.
  • [16] Fu Y.J., Yin L.T., Liang A.H., Zhang C.F., Wang W., Chai B.F., Fan X.J., Therapeutic potential of chlorotoxin-like neurotoxin from the Chinese scorpion for humangliomas, Neurosci Lett., 412(1) (2007) 62-7.
  • [17] Mamelak A.N., Jacoby D.B., Targeted Delivery of Antitumoral Therapy to Glioma and Other Malignancies with Synthetic Chlorotoxin (TM-601), Expert Opin Drug Deliv., 4(2) (2007) 175-86.
  • [18] Stampa S., A field trial comparing the efficacy of sulphamonomethoxine, penicillin, and tarantula poison in the treatment of pododermatitis circumspecta of cattle, J S Afr Vet Assoc., 57(2) (1986) 91–3.
  • [19] Cam Y., Kibar M., Atasever A., Atalay O., Beyaz L., Efficacy of levamisole and Tarantula cubensis venom for the treatment of bovine cutaneous papillomatosis, Vet Rec., 160(14) (2007) 486–8.
  • [20] Icen H., Sekin S., Simsek 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.
  • [21] Paksoy Z., Gülesci 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) 704–8.
  • [22] Sardari K., Kakhki E.G., Mohri M., Evaluation of wound contraction and epithelialization after subcutaneous administration of TheranekronR in cows, Comp Clin Path., 16(3) (2007) 197–200.
  • [23] Gultiken N., Guvenc T., Kaya D., Agaoglu A.R., Ay S.S., Kucukaslan I., Emre B., Findik M., Schafer-Somi S., Aslan S., Tarantula cubensis extract alters the degree of apoptosis and mitosis in canine mammary adenocarcinomas, J Vet Sci., 16(2) (2015) 213–9.
  • [24] Al-Asmari A.K., Riyasdeen A., Al-Shahrani M.H., Islam M., Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines, Onco Targets Ther., 15 (2022) 1289.
  • [25] Akhtar B., Muhammad F., Sharif A., Anwar M.I., Mechanistic insights of snake venom disintegrins in cancer treatment, Eur J Pharmacol., 899 (2021) 174022.
  • [26] Chong H.P., Tan K.Y., Tan C.H., Cytotoxicity of snake venoms and cytotoxins from two southeast Asian cobras (Naja sumatrana, Naja kaouthia): exploration of anticancer potential, selectivity, and cell death mechanism, Front Mol Biosci., 7 (2020) 583587.
  • [27] Orrenius S., Gogvadze V., Zhivotovsky B., Mitochondrial Oxidative Stress: Implications for Cell Death, Annu Rev Pharmacol Toxicol., 47 (2007) 143-183.
  • [28] Yokoyama C., Sueyoshi Y., Ema M., Mori Y., Takaishi K., Hisatomi H., Induction of oxidative stress by anticancer drugs in the presence and absence of cells, Oncol Lett., 14(5) (2017) 6066-70.
  • [29] Çamlı Pulat Ç., In vitro cytotoxic activity of Tarantula cubensis alcoholic extract on different human cell lines. Cumhuriyet Sci. J., 42(2) (2021) 252-259.
  • [30] Ilhan S., Can a Veterinary Drug be Repurposed for Human Cancers?: Cytotoxic Effect of Tarantula cubensis Venom on Human Cancer Cells. Journal of the Institute of Science and Technology, 11(3) (2021) 1763-1769.
  • [31] Andreyev A.Y., Kushnareva Y.E., Starkov A.A., Mitochondrial metabolism of reactive oxygen species, Biochemistry, 70 (2005) 200–214.
  • [32] Vermes I., Haanen C., Steffens-Nakken H., Reutelingsperger C., A novel assay for apoptosis Flow cytometric detection of phosphatidylserine early apoptotic cells using fluorescein labelled expression on Annexin V. Journal of Immunological Methods, 184 (1995) 39-51
  • [33] Dasari M., Acharya A.P., Kim D., Lee S., Lee S., Rhea J., Molinaro R., Murthy N., H-gemcitabine: A new gemcitabine prodrug for treating cancer, Bioconjugate Chem., 24 (2013) 4–8.
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Biyokimya ve Hücre Biyolojisi (Diğer)
Bölüm Natural Sciences
Yazarlar

Deniz Şumnulu 0009-0009-0693-3569

Yayımlanma Tarihi 28 Mart 2024
Gönderilme Tarihi 20 Eylül 2023
Kabul Tarihi 25 Şubat 2024
Yayımlandığı Sayı Yıl 2024Cilt: 45 Sayı: 1

Kaynak Göster

APA Şumnulu, D. (2024). Cytotoxic Effects of Theranekron D6 on HepG2 Heaptocellular Carcinoma Cells. Cumhuriyet Science Journal, 45(1), 8-14. https://doi.org/10.17776/csj.1363685
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