Gülçin TEZCAN, Seçil AK AKSOY, Saliha ŞAHİN, Berrin TUNCA, Gülşah ÇEÇENER

The In-Vitro Impact of Punica Granutum L. (Pomegranate) Juice on Colorectal Cancer Tumors with TP53 and KRAS Mutation

Objective: Colorectal cancer (CRC) is one of the most common human malignancies. A cure for CRC with TP53 and KRAS mutations remains elusive. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required. Induction of tumor cell death by certain phytochemicals derived from medicinal herbs has become a new frontier for cancer therapy research. Although the cancer suppressive effect of Punica granutum L (pomegranate) juice (PGJ) has been determined in CRC, the effect of PGJ depend on mutation status has not been investigated. Material and Method: The anti-proliferative activity of PGJ was tested in the SW480 cell line using the WST-1 assay. To determine the effect of PGJ on cell cycle and apoptosis progression in TP53 and KRAS mutated CRC, the expression levels of BIRC5, CCND1 and BCL2 were analyzed in SW480 cells using RT-qPCR. Results: According to the obtained data, PGJ contains 8,68 ± 0,168 mg/ml ellagic acid. 4% concentration of PGJ inhibited 50% of SW480 cell proliferation in 24h incubation and induced apoptosis though decreasing BCL2 mRNA expression level. Conclusion: The current study is the first to demonstrate the effect of PGJ on modulation of anti-apoptotic gene expression in a TP53 and KRAS mutated CRC cell line which implies the anti-tumor activity independent from p53 and K-Ras signaling pathways. Further studies and validations are required, we suggest that PGJ may be a strong candidate for studies of therapeutic cancer drugs for patients with TP53 and KRAS mutated CRC.

Punica Granutum L. (Nar) Suyunun TP53 ve KRAS Mutasyonu Taşıyan Kolorektal Kanser Tümörlerindeki İn-Vitro Etkisi

Amaç: Kolorektal kanser (KRK) insanlarda en yaygın görülen kanser türlerinden birisidir. TP53 ve KRAS mutasyonları taşıyan KRK hastalarının tedavisinde hala yeterince başarı sağlanamamıştır. Bu nedenle, bu hastaların tedavisi için daha etkin terapötik yaklaşımların geliştirilmesi gerekmektedir. Günümüzde gerçekleştirilmekte olan kanser tedavisi araştırmalarında şifalı bitkilerden elde edilen bazı fitokimyasalların kanser hücrelerinin ölümünü tetiklenme yeteneği üzerinde önemle durulmaktadır. Punica granutum L (nar) suyunun kanser baskılayıcı etkisi KRK'de belirlenmesine rağmen, nar suyunun mutasyon durumuna bağlı etkisi henüz araştırılmamıştır. Gereç ve Yöntem: WST-1 testi kullanılarak nar suyunun SW480 hücreleri üzerindeki anti-proliferatif etkisi belirlendi. Nar suyu muamelesi sonrası, RT-qPCR yöntemi ile BIRC5, CCND1 ve BCL2 genlerinin ekspresyon seviyeleri saptanarak TP53 ve KRAS mutasyonlu KRK tümörlerinde nar suyunun apoptoz üzerindeki etkisi değerlendirildi. Bulgular: İçeriğinde 8,68 ± 0,168 mg / mL ellagik asit içerdiği belirlediğimiz nar suyunun %4’lük konsantrasyonunun 24 saat inkübasyon süresinde SW480 hücre proliferasyonunu %50 oranında azalttığı ve BCL2 mRNA ekspresyon seviyesini düşürerek apoptozu tetiklediği saptandı. Sonuç: Mevcut çalışma, nar suyunun TP53 ve KRAS mutasyonlu KRK hücrelerinde anti-apoptotik genlerin ekspresyon seviyelerini değiştirerek TP53 ve KRAS sinyal yolaklarından bağımsız olarak anti-tümör etkisine yol açtığını gösteren ilk çalışmadır. İleri araştırmalara ve doğrulamaya gereksinim olmakla birlikte bulgularımız, nar suyunun TP53 ve KRAS mutasyonlu KRK hastaları için ilaç araştırmalarına güçlü bir aday olabileceğini göstermektedir.

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