6,3'-dimethoxy flavonol: Evidence-based insights into anti-proliferative and apoptotic effect on osteosarcoma cells

Abstract

Osteosarcoma, a cancer predominantly affecting children and teenagers, has shown limited improvements in long-term survival rates despite advances in treatment, necessitating new therapeutic approaches. Natural compounds, particularly flavonoids, are being investigated for their anti-cancer properties due to their ability to modulate signaling pathways and induce apoptosis in cancer cells. This study evaluates the anti-carcinogenic effects of 6,3'-dimethoxy flavonol on MG-63 osteosarcoma cells, a p53-null model suitable for testing novel therapies, using various assays. Cell viability and proliferation were measured via MTT assay, showing dose dependent inhibition with an IC50 of 221.017 µg/ml at 48 hours. Phase-contrast microscopy revealed morphological changes consistent with apoptosis, including cell shrinkage, reduced density and cytoplasmic blebbing. Wound healing assays demonstrated significant inhibition of cell migration at 100 µg/ml and 234.12 µg/ml, highlighting its anti-metastatic potential. Acridine orange/ethidium bromide (AO/EB) staining confirmed apoptotic cell death. Real-time PCR analysis revealed an increased (Bax/Bcl-2) ratio and upregulation of p53 expression, indicating activation of the intrinsic apoptotic pathway. These findings demonstrate that 6,3'-dimethoxy flavonol effectively induces apoptosis and inhibits migration in MG-63 cells by modulating apoptotic markers and signaling pathways. The results suggest its potential as a therapeutic agent for osteosarcoma. Future studies should explore itsinvivo efficacy, possible synergistic effects in combination therapies, and its mechanisms in p53-positive cell lines. This evidence underscores the promise of flavonoid based interventions in cancer treatment.

Keywords

• 6,3'-dimethoxy flavonol
• Cell Viability
• Metastasis inhibition
• Metastasis inhibition Cell viability

Abstract

Çoğunlukla çocukları ve gençleri etkileyen bir kanser türü olan osteosarkom, tedavi alanındaki gelişmelere rağmen uzun süreli sağkalım oranlarında sınırlı iyileşmeler göstermiş, bu durum da yeni tedavi yaklaşımlarını gerekli kılmıştır. Doğal bileşikler, özellikle de flavonoidler, kanser hücrelerinde sinyal yollarını düzenleme ve apoptozu başlatma kabiliyetlerine bağlı olarak kanser karşıtı özellikleri açısından araştırılmaktadır. Bu çalışmada, 6,3'-dimetoksi flavonolün yeni tedavilerin test edilmesine uygun bir model olan MG-63 osteosarkom hücreleri üzerindeki antikarsinojenik etkileri çeşitli analizler kullanılarak değerlendirilmiştir. MTT testi ile hücre canlılığı ve çoğalması ölçülmüş ve 48 saatte 221.017 µg/ml'lik bir IC50 ile doza bağlı bir inhibisyon tespit edilmiştir. Faz-kontrast mikroskopisi incelemesi, hücre büzülmesi, yoğunluğun azalması ve sitoplazmik kabarcıklanma gibi apoptozla uyumlu morfolojik değişiklikleri ortaya koymuştur. Yara iyileşme deneyleri, 100 µg/ml ve 234,12 µg/ml'de hücre göçünün önemli ölçüde inhibe edildiğini göstererek 6,3'-dimethoxy flavonolün anti-metastatik potansiyelini öne çıkarmıştır. Uygulanan Akridin turuncusu/etidyum bromür (AT/EB) boyaması apoptotik hücre ölümünü doğrulamıştır. Bax/Bcl-2 oranında artış ve p53 ekspresyonunda artış olduğunu ortaya koyan gerçek zamanlı PCR analizi, intrinsik apoptotik yolağın aktive olduğunu göstermiştir. Bu bulgular, 6,3'-dimetoksi flavonolün apoptotik belirteçleri ve sinyal yollarını düzenleyerek MG-63 hücrelerinde apoptozu etkili bir şekilde indüklediğini ve hücre göçünü engellediğini göstermektedir. Sonuçlar, 6,3'-dimetoksi flavonolün osteosarkom için tedavi edici bir ajan olarak potansiyeli olduğunu da göstermektedir. Gelecek çalışmalarda 6,3'-dimetoksi flavonolün in vivo etkinliği, kombinasyon tedavilerindeki olası sinerjik etkileri ve p53 pozitif hücre hatlarındaki mekanizmaları araştırılmalıdır. Çalışmada sunulan kanıtlar, kanser tedavisinde flavonoid bazlı müdahalelerin umut verici olduğunun altını çizmektedir.

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