İnsan Kolorektal Adenokarsinom (CaCo-2) Hücre Hattında Teranekron ve Doksorubisinin Sitotoksik Etkisi

Yıl 2022, , 79 - 83, 30.12.2022

Numan Taşpınar , Muhammed Sait Ertuğrul

https://doi.org/10.33713/egetbd.1192800

Öz

AMAÇ: Bu çalışmada veteriner hekimlikte sıklıkla kullanılan Teranekronun insan kolorektal adenokarsinomu üzerinde antineoplastik etkinliğinin değerlendirilmesi amaçlandı.
GEREÇ VE YÖNTEM: Çalışmada etkinliğini değerlendirmek için Teranekron (TRN) ve pozitif kontrol olarak da antineoplastik ilaç olan Doksorubisin kullanıldı. İnsan kolorektal hücre hattı CaCo-2 üzerinde Teranekronun sitotoksik etkinliği araştırıldı. Canlılık oranları belirlenmesinde MTT proliferasyonu testi uygulandı. İstatistiksel analizler için ise ANOVA Tukey testi kullanıldı ve anlamlılık düzeyi P<0,01 olarak kabul edildi.
BULGULAR: Canlılık testleri yaptığımızda Teranekronun tek olarak uygulandığı gruplarda Teranekronun doza bağlı olarak toksisitesinin arttığı görüldü. 10 µM konsantrasyonda CaCo-2 canlılığı %94 iken 100 µM’lık konsantrasyonda canlılık oranı % 79 a düştü. Sadece pozitif kontrol olarak uyguladığımız Dox 40 µM konsantrasyonunda canlılık %78,72 Dox 40 µM + TRN 100 µM uygulandığı grupta ise canlılık oranı %73 olarak belirlendi. Dox+TRN’nin birlikte uygulandığı gruplarda TRN 50 µM dozundan itibaren toksik etki oranı konsantrasyona bağlı olarak artmaya başladı.
SONUÇLAR: Teranekronun CaCo-2 hücre hattı üzerinde yapılan canlılık testi sonucunda doza bağlı olarak TRN’nin sitotoksik etkinliğinin arttığı belirlendi. Teranekron etkinliği antineoplastik ilaç olarak kullanılan Doksorubisin ile karşılaştırıldığında ise 75 µM TRN’nin 40 µM Dox ile aynı etki ortay çıkarttığı belirlendi. Yan etki profilleri düşünülecek olursa daha az yan etki gösteren TRN insan kolorektal kanser tedavisinde alternatif bir tedavi olma potansiyeli olduğu görülmektedir. TRN’nin antikanser tedavisi kullanılmasının tavsiye edilmesi için daha detaylı çalışmalara ihtiyaç bulunmaktadır.

Anahtar Kelimeler

CaCo-2, Doksorubisin, İnsan Kolorektal Adenokarsinom, Teranekron, TRN

Cytotoxic Effect of Teranecrone and Doxorubicin on Human Colorectal Adenocarcinoma (CaCo-2) Cell Line

Öz

OBJECTİVE: In this study, it was aimed to evaluate the antineoplastic efficacy of Teranecron, which is frequently used in veterinary medicine, on human colorectal adenocarcinoma.
MATERİALS AND METHODS: Teranecron (TRN) was used to evaluate its effectiveness in the study, and the antineoplastic drug Doxorubicin was used as a positive control. The cytotoxic activity of Teranecron on the human colorectal cell line CaCo-2 was investigated. MTT proliferation test was used to determine the viability rates. ANOVA Tukey test was used for statistical analysis and the level of significance was accepted as P<0.01.
RESULTS: When we performed viability tests, it was observed that the toxicity of Teranecron increased in a dose-dependent manner in the groups in which Teranecron was administered alone. While the viability of CaCo-2 at 10 µM concentration was 94%, the viability rate at 100 µM concentration decreased to 79%. The viability was determined as 78.72% in the Dox 40 µM concentration, which we applied only as a positive control, and 73% in the group in which Dox 40 µM + TRN 100 µM was applied. In the groups where Dox+TRN was administered together, the toxic effect ratio started to increase depending on the concentration, starting from the TRN 50 µM dose.
RESULTS: As a result of the viability test of teranecron on the CaCo-2 cell line, it was determined that the cytotoxic activity of TRN increased in a dose-dependent manner. When teranechron efficacy was compared with Doxorubicin used as an antineoplastic drug, it was determined that 75 µM TRN had the same effect as 40 µM Dox. Considering the side-effect profiles, TRN with fewer side effects seems to have the potential to be an alternative treatment for human colorectal cancer. More detailed studies are needed to recommend the use of TRN as an anticancer therapy.

Anahtar Kelimeler

CaCo-2, Doxorubicin, Human Colorectal Adenocarcinoma, Teranecrone, TRN

Kaynakça

• 1. Pingel S. [Homeopathy. Basic aspects and principles of use in dermatology]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 1992;43(8):475-82.
• 2. Merrell WC, Shalts E. Homeopathy. The Medical clinics of North America. 2002;86(1):47-62.
• 3. Pirvu L, Stefaniu A, Neagu G, Pintilie L. Studies on Anemone nemorosa L. extracts; polyphenols profile, antioxidant activity, and effects on Caco-2 cells by in vitro and in silico studies. Open Chemistry. 2022;20(1):299-312.
• 4. Woods JA, Jewell C, O'Brien NM. Sedanolide, a Natural Phthalide from Celery Seed Oil: Effect on Hydrogen Peroxide and tert-Butyl Hydroperoxide-Induced Toxicity in HepG2 and CaCo-2 Human Cell Lines. In Vitro & Molecular Toxicology. 2001;14(3):233-40.
• 5. Benkendorff K, McIver CM, Abbott CA. Bioactivity of the <i>Murex</i> Homeopathic Remedy and of Extracts from an Australian Muricid Mollusc against Human Cancer Cells. Evidence-Based Complementary and Alternative Medicine. 2011;2011:879585.
• 6. Tosun NG, Kaplan Ö, Özgür A. Apoptosis Induced by Tarantula cubensis Crude Venom (Theranekron® D6) in Cancer Cells. Revista Brasileira de Farmacognosia. 2021;31(6):824-31.
• 7. Sardari K, Kakhki EG, Mohri M. Evaluation of wound contraction and epithelialization after subcutaneous administration of Theranekron® in cows. Comparative Clinical Pathology. 2007;16(3):197-200.
• 8. Sencar L, Coşkun G, Şaker D, Sapmaz T, Kara S, Çelenk A, et al. Effects of Theranekron and alpha-lipoic acid combined treatment on GAP-43 and Krox-20 gene expressions and inflammation markers in peripheral nerve injury. Ultrastructural pathology. 2021;45(3):167-81.
• 9. Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009;27(1):127-45.
• 10. Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. Journal of the American College of Cardiology. 2014;64(9):938-45.
• 11. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA: A Cancer Journal for Clinicians. 2020;70(3):145-64.
• 12. Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. The New England journal of medicine. 2005;352(5):476-87.
• 13. Cam Y, Kibar M, Atasever A, Atalay O, Beyaz L. Efficacy of levamisole and Tarantula cubensis venom for the treatment of bovine cutaneous papillomatosis. The Veterinary record. 2007;160(14):486-8.
• 14. Paksoy Z, Gülesci N, Kandemir FM, Dincel GC. Effectiveness of levamisole and tarantula cubensis extract in the treatment of teat Papillomatosis of cows. Indian Journal of Animal Research. 2015;49:704-8.
• 15. Icen H, Sekin S, Simsek A, Kochan A, Tunik S. The Efficacy of Tarantula cubensis Extract (Theranekron) in Treatment of Canine Oral Papillomatosis. Asian Journal of Animal and Veterinary Advances. 2011;6:744-9.
• 16. Koch H, Stein M. Konservative Behandlung von Neoplasmen der Milchdruse des Hundes mit Theranekron. Praktische Tierarzt. 1980.
• 17. Gultiken N, Guvenc T, Kaya D, Agaoglu AR, Ay SS, Kucukaslan I, et al. Tarantula cubensis extract alters the degree of apoptosis and mitosis in canine mammary adenocarcinomas. Journal of veterinary science. 2015;16(2):213-9.
• 18. Er A, Çorum O, Corum DD, Hitit M, Donmez H, Guzeloglu A. Alcoholic extract of Tarantula cubensis induces apoptosis in MCF-7 cell line. Biomedical Research-tokyo. 2017;28:3660-5.
• 19. Ghasemi-Dizgah A, Nami B, Amirmozafari N. Tarantula cubensis venom (theranekron^&#174;) selectively destroys human cancer cells via activating caspase-3-mediated apoptosis. Acta Medica International. 2017;4(1):74-80.