ORSİNOL’ÜN SW480 İNSAN KOLOREKTAL KANSER HÜCRELERİNDE PROLİFERASYON VE APOPTOZ ÜZERİNE ETKİLERİ

Öz

Amaç: Kolorektal kanser, her yıl dünya çapında hızla artan bir hastalıktır. Teşhis konulmuş hastaların neredeyse yarısı her yıl bu hastalıktan hayatını kaybetmektedir. Kolorektal kanserin tedavisi için uygulanan geleneksel tedavi yöntemleri olan cerrahi, radyoterapi ve mevcut kemoterapi seçenekleri de dahil olmak üzere tedavide kullanılan yöntemlerin etkinliği düşüktür ve çok fazla yan etkileri bulunmaktadır. Tüm bu problemler nedeni ile kolorektal kanserin tedavisi için yeni ajanlar geliştirmenin önemi giderek artmaktadır. Orsinol, likenlerden izole edilen bir sekonder metabolit olup, söz konusu bileşiğin antioksidan, antimikrobiyal ve antidepresan aktivitesine yönelik bulgular mevcuttur. Son yıllarda bileşiğin antikanser etkinliğine dair araştırmalar da literatürde yer almaya başlamıştır. Bu çalışmada, orsinolün insan SW480 kolorektal kanser hücrelerinde hücre proliferasyonu ve apoptoz üzerine etkinliğinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışma kapsamında SW480 insan kolorektal kanser hücreleri kullanılmış ve DMEM besiyerinde kültüre edilmiştir. Orsinol, dimetilsülfoksit ile çözülerek stok çözeltisi hazırlanmış ve hücrelere 1-25 mM konsantrasyon aralığında uygulanmıştır. Orsinolün hücre canlılığı üzerine etkisi MTT testi ile belirlenmiştir. Bileşiğin apoptotik etkinliği Annexin V bağlanma analizi ile Muse Hücre Analiz cihazı kullanılarak değerlendirilmiştir. Sonuç ve Tartışma: MTT analiz sonuçları, orsinolün 5 mM ve üzerinde hücre canlılığını doza bağlı olarak anlamlı şekilde azalttığını gösterdi (p<0.05). Kontrol grubunda hücre canlılığı 100.00±6.14% iken, 25 mM orsinol uygulanan hücrelerde canlılık 12.50±0.65% olarak belirlendi (p<0.0001). Annexin V bağlanma analizi bulgularına göre erken apoptotik hücre popülasyonu 25 mM orsinol uygulanan grupta 12.06±1.22% iken, kontrol grubunda 0.60±0.11% olarak belirlendi. Çalışmadan elde edilen bulgular, orsinol’ün, SW480 kolorektal kanser hücreleri üzerinde yüksek konsantrasyonda sitotoksik etkili olduğunu göstermiş olup, daha ileri çalışmalar ile bileşiğin etkinliğinin artırılmasına ve etki mekanizmasının aydınlatılmasına ihtiyaç duyulmaktadır.

Anahtar Kelimeler

• Apoptoz
• kolorektal kanser
• orsinol
• proliferasyon
• SW480

THE EFFECTS OF ORCINOL ON PROLIFERATION AND APOPTOSIS OF SW480 HUMAN COLORECTAL CANCER CELLS

Öz

Objective: Colorectal cancer is a rapidly increasing disease worldwide, and almost half of the diagnosed patients die from this disease each year. The methods used in the treatment of colorectal cancer, including traditional treatment methods such as surgery, radiotherapy and current chemotherapy options, have low effectiveness and have many side effects. Because of all these problems, the importance of developing new agents for the treatment of colorectal cancer is increasing. Orsinol is a secondary metabolite isolated from lichens, and there are findings regarding the antioxidant, antimicrobial and antidepressant activity of the compound. In recent years, research on the anticancer activity of the compound has also started to take place in the literature. In this study, it was aimed to investigate the efficacy of orcinol on cell proliferation and apoptosis in human SW480 colorectal cancer cells. Material and Method: Within the scope of the study, SW480 human colorectal cancer cells were used and cultured in DMEM medium. Orcinol was dissolved with dimethylsulfoxide to prepare a stock solution and applied to the cells in a concentration range of 1-25 mM. The effect of orcinol on cell viability was determined by MTT test. The apoptotic activity of the compound was evaluated with Annexin V binding assay using the Muse Cell Analyzer. Result and Discussion: The results of MTT analysis showed that orcinol significantly decreased cell viability at 5 mM and above (p<0.05). While cell viability was 100.00±6.14% in the control group, it was determined as 12.50±0.65% in cells treated with 25 mM orcinol (p<0.0001). According to Annexin V binding analysis findings, the early apoptotic cell population was 12.06±1.22% in the 25 mM orcinol treated group, while it was 0.60±0.11% in the control group. The findings obtained from the study showed that that orcinol has a cytotoxic effect at high concentration on SW480 colorectal cancer cells, and further studies are needed to increase the efficiency of the compound and to elucidate its mechanism of action.

Anahtar Kelimeler

• Apoptosis
• colorectal cancer
• orcinol
• proliferation
• SW480.

Kaynakça

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