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In vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS

Year 2021, Volume: 22 Issue: 2, 173 - 177, 15.10.2021
https://doi.org/10.23902/trkjnat.901480

Abstract

Cancer, which is the second most common cause of death after cardiovascular diseases, is one of the most important health problems of today. Discovery of effective treatments and drugs are important in cancer treatment. The COVID-19 epidemic, which broke out in Wuhan province of China in December 2019 and is considered as a pandemic worldwide, affected millions of people. The SARS-CoV-2 virus, which causes this epidemic, affects the lungs, heart, brain, kidneys, gastrointestinal system, ovaries and testicles and various drugs are used in the treatment. In this study, we aimed to determine the cytotoxic effect of favipiravir, dornase alfa and ivermectin, which are drugs used in the treatment of COVID-19, on human lung cancer cell line (A549). Favipiravir, dornase alfa and ivermectin concentrations were prepared in doubly increasing doses (0.5-64 µg/mL). The prepared concentrations were tested on human A549 cells. After 24 hours of incubation, the cytotoxic effects of the drugs on cancer cells were detected by the MTT (3-(4,5-dimethylthiazol-2-yl)-diphenyl tetrazolium bromide) method. The results were given as % viability. It was determined that favipiravir, dornase alfa and ivermectin significantly decreased the cell viability in lung cancer cell line with increasing application doses (p<0.05). 

Supporting Institution

The Scientific and Technological Research Council of Turkey (TÜBİTAK), 2209-A - Research Project Support Programme for Undergraduate Students

Project Number

1919B012001203, 1919B012001217, 1919B012001262

References

  • 1. Chaccour, C., Hammann, F., Ramón-García, S. & Rabinovich, N.R. 2020. Ivermectin and COVID-19: keeping rigor in times of urgency. American Journal of Tropical Medicine and Hygiene, 102(6): 1156.
  • 2. Chen, L., Bi, S., Wei, Q., Zhao, Z., Wang, C. & Xie, S. 2020. Ivermectin suppresses tumour growth and metastasis through degradation of PAK1 in oesophageal squamous cell carcinoma. Journal of Cellular and Molecular Medicine, 24(9): 5387-5401.
  • 3. Coomes, E.A. & Haghbayan, H. 2020. Favipiravir, an antiviral for COVID-19? Journal of Antimicrobial Chemotherapy, (75)7: 2013-2014.
  • 4. Huang, W.Y. Cai, Y.Z. & Zhang, Y. 2010. Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutrition and Cancer, 62(1): 1-20.
  • 5. Jackson, AL. & Loeb, L.A. 2001. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutation Research, 477: 7-21.
  • 6. Joshi, S., Parkar, J., Ansari, A., Vora, A., Talwar, D., Tiwaskar, M., Patil, S. & Barkate, H. 2021. Role of favipiravir in the treatment of COVID-19. International Journal of Infectious Diseases, 102: 501-508.
  • 7. Kaushik, I., Ramachandran, S., Prasad, S. & Srivastava, S.K. 2020. Drug rechanneling: a novel paradigm for cancer treatment. Seminars in Cancer Biology, 68: 279-290. 8. Khan, M.S.I., Khan, M.S.I., Debnath, C.R., Nath, P.N., Al Mahtab, M., Nabeka, H., Matsuda, S. & Akbar, S.M.F. 2020. Ivermectin Treatment May Improve the Prognosis of Patients with COVID-19. Archivos de Bronconeumologia, 56(12): 828.
  • 9. Koran, K., Tekin, Ç., Çalışkan, E., Tekin, S., Sandal, S. & Görgülü, A.O. 2017. Synthesis, structural and thermal characterizations and in vitro cytotoxic activities of new cyclotriphosphazene derivatives. Phosphorus, Sulfur, and Silicon and the Related Elements, 192: 1002-1011.
  • 10. Melotti, A., Mas, C., Kuciak, M., Lorente-Trigos, A., Borges, I. & Ruiz i Altaba, A. 2014. The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. EMBO Molecular Medicine, 6: 1263-1278.
  • 11. Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65: 55-63.
  • 12. Nagakrishna, L. & Thawanı, V. 2020. Favipiravir in COVID-19. The Antiseptic, 117: 16-17.
  • 13. Nambara, S., Masuda, T., Nishio, M., Kuramitsu, S., Tobo, T., Ogawa, Y., Hu, Q., Iguchi, T., Kuroda, Y., Ito, S., Eguchi, H., Sugimachi, K., Saeki, H., Oki, E., Maehara, Y. & Suzuki, A. & Mimori, K. 2017. Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer. Oncotarget, 8(64): 107666-107677.
  • 14. Nettore, I.C., Colao, A. & Macchia, P.E. 2018. Nutritional and Environmental Factors in Thyroid Carcinogenesis. International Journal of Environmental Research and Public Health, 15(8): 1735.
  • 15. Okur, H.K., Yalcin, K., Tastan, C., Demir, S., Yurtsever, B., Karakus, G.S., Kancagi, D.D., Abanuz, S., Seyis, U., Zengin, R., Hemsinlioglu, C., Kara, M., Yildiz, M.E., Deliceo, E., Birgen, N., Pelit, N.B., Cuhadaroglu, C., Kocagoz, A.S. & Ovali, E. 2020. Preliminary report of in vitro and in vivo effectiveness of dornase alfa on SARS-CoV-2 infection. New Microbes and New Infections, 37: 100756.
  • 16. Potì, F., Pozzoli, C., Adami, M., Poli, E. & Costa, L.G. 2020. Treatments for COVID-19: emerging drugs against the coronavirus. Acta Bio Medica Atenei Parmensis, 91(2): 118.
  • 17. Serda, I.F.B.C., van Roekel, E. & Lynch, B.M. 2018. The Role of Physical Activity in Managing Fatigue in Cancer Survivors. Current Nutrition Reports, 7(3): 59-69.
  • 18. Sharmeen, S., Skrtic, M., Sukhai, M.A., Hurren, R., Gronda, M. & Wang X. 2010. The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. Blood, 116(18): 3593-3603.
  • 19. Sivanandam, A., Murthy, S., Kim, S.H., Barrack, E.R. & Veer Reddy GP. 2010. Role of androgen receptor in prostate cancer cell cycle regulation: interaction with cell cycle regulatory proteins and enzymes of DNA synthesis. Current Protein & Peptide Science, 11: 451-458.
  • 20. Varkaris, A., Katsiampoura, A.D., Araujo, J.C., Gallick, G.E. & Corn, P.G. 2014. Src signaling pathways in prostate cancer. Cancer and Metastasis Reviews, 33: 595-606.
Year 2021, Volume: 22 Issue: 2, 173 - 177, 15.10.2021
https://doi.org/10.23902/trkjnat.901480

Abstract

Kalp damar hastalıklarından sonra ikinci ölüm nedeni olan kanser, günümüzün en önemli sağlık sorunlarından biridir. Etkili tedavilerin ve yeni ilaçların keşfedilmesi kanser tedavisinde önem arz etmektedir. Aralık 2019'da Çin'in Wuhan eyaletinde patlak veren ve dünya çapında bir salgın olarak kabul edilen COVID-19 salgını milyonlarca insanı etkilemektedir. Bu salgına neden olan SARS-CoV-2 virüsü başta akciğerleri olmak üzere kalbi, beyni, böbrekleri, gastrointestinal sistemi, yumurtalık ve testisleri etkilemekte ve tedavisinde çeşitli ilaçlar kullanılmaktadır. Bu çalışmada, COVID-19 tedavisinde kullanılan ilaçlar olan favipiravir, dornaz alfa ve ivermektinin insan akciğer kanseri hücre hattı (A549) üzerindeki sitotoksik etkisinin belirlenmesi amaçlanmıştır. Çalışmada favipiravir, dornaz alfa ve ivermektin ilaçlarının konsantrasyonları iki kat artan dozlarda (0,5-64 µg/mL) hazırlandı. Hazırlanan konsantrasyonlar, insan A549 hücreleri üzerine uygulandı. 24 saatlik inkübasyondan sonra, ilaçların hücre hatları üzerindeki sitotoksik etkileri, MTT (3-(4,5-dimetiltiyazol-2-il)-difenil tetrazolyum bromür) yöntemi ile tespit edildi. Sonuçlar % canlılık olarak verildi. Artan doza bağlı olarak favipiravir, dornaz alfa ve ivermektinin akciğer kanseri hücre dizisinde hücre canlılığını önemli ölçüde azalttığı belirlendi (p<0.05).

Project Number

1919B012001203, 1919B012001217, 1919B012001262

References

  • 1. Chaccour, C., Hammann, F., Ramón-García, S. & Rabinovich, N.R. 2020. Ivermectin and COVID-19: keeping rigor in times of urgency. American Journal of Tropical Medicine and Hygiene, 102(6): 1156.
  • 2. Chen, L., Bi, S., Wei, Q., Zhao, Z., Wang, C. & Xie, S. 2020. Ivermectin suppresses tumour growth and metastasis through degradation of PAK1 in oesophageal squamous cell carcinoma. Journal of Cellular and Molecular Medicine, 24(9): 5387-5401.
  • 3. Coomes, E.A. & Haghbayan, H. 2020. Favipiravir, an antiviral for COVID-19? Journal of Antimicrobial Chemotherapy, (75)7: 2013-2014.
  • 4. Huang, W.Y. Cai, Y.Z. & Zhang, Y. 2010. Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutrition and Cancer, 62(1): 1-20.
  • 5. Jackson, AL. & Loeb, L.A. 2001. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutation Research, 477: 7-21.
  • 6. Joshi, S., Parkar, J., Ansari, A., Vora, A., Talwar, D., Tiwaskar, M., Patil, S. & Barkate, H. 2021. Role of favipiravir in the treatment of COVID-19. International Journal of Infectious Diseases, 102: 501-508.
  • 7. Kaushik, I., Ramachandran, S., Prasad, S. & Srivastava, S.K. 2020. Drug rechanneling: a novel paradigm for cancer treatment. Seminars in Cancer Biology, 68: 279-290. 8. Khan, M.S.I., Khan, M.S.I., Debnath, C.R., Nath, P.N., Al Mahtab, M., Nabeka, H., Matsuda, S. & Akbar, S.M.F. 2020. Ivermectin Treatment May Improve the Prognosis of Patients with COVID-19. Archivos de Bronconeumologia, 56(12): 828.
  • 9. Koran, K., Tekin, Ç., Çalışkan, E., Tekin, S., Sandal, S. & Görgülü, A.O. 2017. Synthesis, structural and thermal characterizations and in vitro cytotoxic activities of new cyclotriphosphazene derivatives. Phosphorus, Sulfur, and Silicon and the Related Elements, 192: 1002-1011.
  • 10. Melotti, A., Mas, C., Kuciak, M., Lorente-Trigos, A., Borges, I. & Ruiz i Altaba, A. 2014. The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. EMBO Molecular Medicine, 6: 1263-1278.
  • 11. Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65: 55-63.
  • 12. Nagakrishna, L. & Thawanı, V. 2020. Favipiravir in COVID-19. The Antiseptic, 117: 16-17.
  • 13. Nambara, S., Masuda, T., Nishio, M., Kuramitsu, S., Tobo, T., Ogawa, Y., Hu, Q., Iguchi, T., Kuroda, Y., Ito, S., Eguchi, H., Sugimachi, K., Saeki, H., Oki, E., Maehara, Y. & Suzuki, A. & Mimori, K. 2017. Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer. Oncotarget, 8(64): 107666-107677.
  • 14. Nettore, I.C., Colao, A. & Macchia, P.E. 2018. Nutritional and Environmental Factors in Thyroid Carcinogenesis. International Journal of Environmental Research and Public Health, 15(8): 1735.
  • 15. Okur, H.K., Yalcin, K., Tastan, C., Demir, S., Yurtsever, B., Karakus, G.S., Kancagi, D.D., Abanuz, S., Seyis, U., Zengin, R., Hemsinlioglu, C., Kara, M., Yildiz, M.E., Deliceo, E., Birgen, N., Pelit, N.B., Cuhadaroglu, C., Kocagoz, A.S. & Ovali, E. 2020. Preliminary report of in vitro and in vivo effectiveness of dornase alfa on SARS-CoV-2 infection. New Microbes and New Infections, 37: 100756.
  • 16. Potì, F., Pozzoli, C., Adami, M., Poli, E. & Costa, L.G. 2020. Treatments for COVID-19: emerging drugs against the coronavirus. Acta Bio Medica Atenei Parmensis, 91(2): 118.
  • 17. Serda, I.F.B.C., van Roekel, E. & Lynch, B.M. 2018. The Role of Physical Activity in Managing Fatigue in Cancer Survivors. Current Nutrition Reports, 7(3): 59-69.
  • 18. Sharmeen, S., Skrtic, M., Sukhai, M.A., Hurren, R., Gronda, M. & Wang X. 2010. The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. Blood, 116(18): 3593-3603.
  • 19. Sivanandam, A., Murthy, S., Kim, S.H., Barrack, E.R. & Veer Reddy GP. 2010. Role of androgen receptor in prostate cancer cell cycle regulation: interaction with cell cycle regulatory proteins and enzymes of DNA synthesis. Current Protein & Peptide Science, 11: 451-458.
  • 20. Varkaris, A., Katsiampoura, A.D., Araujo, J.C., Gallick, G.E. & Corn, P.G. 2014. Src signaling pathways in prostate cancer. Cancer and Metastasis Reviews, 33: 595-606.
There are 19 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section Research Article/Araştırma Makalesi
Authors

Ahmet Karakuş 0000-0003-1458-808X

Sevgi Ünal Karakuş 0000-0002-6409-7783

Fatma Usta This is me 0000-0002-5583-3785

Ümit Herdem This is me 0000-0002-4059-8284

Sude Aksu This is me 0000-0001-7958-7737

Fatma Özdemir This is me 0000-0002-7978-3700

Mehri Çukurcak This is me 0000-0001-8224-9392

Ecem Çıtakoğlu This is me 0000-0001-5145-0560

Project Number 1919B012001203, 1919B012001217, 1919B012001262
Publication Date October 15, 2021
Submission Date March 23, 2021
Acceptance Date July 5, 2021
Published in Issue Year 2021 Volume: 22 Issue: 2

Cite

APA Karakuş, A., Ünal Karakuş, S., Usta, F., Herdem, Ü., et al. (2021). In vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS. Trakya University Journal of Natural Sciences, 22(2), 173-177. https://doi.org/10.23902/trkjnat.901480
AMA Karakuş A, Ünal Karakuş S, Usta F, Herdem Ü, Aksu S, Özdemir F, Çukurcak M, Çıtakoğlu E. In vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS. Trakya Univ J Nat Sci. October 2021;22(2):173-177. doi:10.23902/trkjnat.901480
Chicago Karakuş, Ahmet, Sevgi Ünal Karakuş, Fatma Usta, Ümit Herdem, Sude Aksu, Fatma Özdemir, Mehri Çukurcak, and Ecem Çıtakoğlu. “In Vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS”. Trakya University Journal of Natural Sciences 22, no. 2 (October 2021): 173-77. https://doi.org/10.23902/trkjnat.901480.
EndNote Karakuş A, Ünal Karakuş S, Usta F, Herdem Ü, Aksu S, Özdemir F, Çukurcak M, Çıtakoğlu E (October 1, 2021) In vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS. Trakya University Journal of Natural Sciences 22 2 173–177.
IEEE A. Karakuş, S. Ünal Karakuş, F. Usta, Ü. Herdem, S. Aksu, F. Özdemir, M. Çukurcak, and E. Çıtakoğlu, “In vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS”, Trakya Univ J Nat Sci, vol. 22, no. 2, pp. 173–177, 2021, doi: 10.23902/trkjnat.901480.
ISNAD Karakuş, Ahmet et al. “In Vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS”. Trakya University Journal of Natural Sciences 22/2 (October 2021), 173-177. https://doi.org/10.23902/trkjnat.901480.
JAMA Karakuş A, Ünal Karakuş S, Usta F, Herdem Ü, Aksu S, Özdemir F, Çukurcak M, Çıtakoğlu E. In vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS. Trakya Univ J Nat Sci. 2021;22:173–177.
MLA Karakuş, Ahmet et al. “In Vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS”. Trakya University Journal of Natural Sciences, vol. 22, no. 2, 2021, pp. 173-7, doi:10.23902/trkjnat.901480.
Vancouver Karakuş A, Ünal Karakuş S, Usta F, Herdem Ü, Aksu S, Özdemir F, Çukurcak M, Çıtakoğlu E. In vitro CYTOTOXIC EFFECTS OF SOME COVID-19 DRUGS ON LUNG CANCER CELLS. Trakya Univ J Nat Sci. 2021;22(2):173-7.

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