Resveratrol Modulates Apoptosis- and Cell Cycle-Related Gene Expression in Ishikawa Endometrial Cancer Cells

Öz

Background: The present study investigated the impact of resveratrol on cellular viability, apoptotic activity, proliferative capacity, and estrogen receptor/PTEN-associated signaling pathways in the ER-positive endometrial cancer cell line Ishikawa. Methods: Ishikawa cells were treated with different concentrations of resveratrol, and cell viability was assessed at 24, 48, and 72 hours using the MTT test. Based on dose-response results, sub-cytotoxic doses (15 and 30 μM) were selected for molecular studies. mRNA expression of apoptosis-related genes (BAX, BCL-2, CASP3), the proliferation marker CCND1, estrogen receptor gene ESR1, and tumor suppressor PTEN was quantified using qRT-PCR. Results: Resveratrol treatment caused a progressive, dose- and time-dependent decrease in Ishikawa cell viability. qRT-PCR analysis demonstrated upregulation of pro-apoptotic BAX and CASP3, downregulation of anti-apoptotic BCL-2 and proliferation-associated CCND1, significant suppression of ESR1, and dose-dependent elevation of PTEN expression. An increased BAX/BCL-2 ratio indicates that cellular homeostasis has shifted towards a pro-apoptotic state. Conclusion: These results indicate that resveratrol promotes pro-apoptotic transcriptional responses and reduces cell viability, potentially associated with changes in genes related to estrogen receptor signaling and PTEN pathways. The observed effects at sub-cytotoxic concentrations suggest resveratrol as a promising candidate for experimental adjunct therapy in ER-positive endometrial cancer models.

Anahtar Kelimeler

• Endometrial cancer
• Resveratrol
• Apoptosis
• Cell Proliferation
• Estrogen Receptor

Resveratrol, Ishikawa Endometriyal Kanser Hücrelerinde Apoptoz ve Hücre Döngüsü ile İlişkili Gen Ekspresyonunu Modüle Eder

Öz

Giriş: Bu çalışma, ER-pozitif endometriyal kanser hücre hattı Ishikawa’da resveratrolün hücre canlılığı, apoptoz, proliferasyon ve östrojen reseptörü/PTEN ile ilişkili yolaklar üzerindeki etkilerini incelemeyi amaçlamıştır. Yöntemler: Ishikawa hücrelerine farklı konsantrasyonlarda resveratrol uygulanmış ve hücre canlılığı 24, 48 ve 72 saatlerde MTT testi ile değerlendirilmiştir. Doz–yanıt sonuçlarına dayanarak moleküler analizler için sub-sitotoksik dozlar (15 ve 30 μM) seçilmiştir. Apoptoz ile ilişkili genlerin (BAX, BCL-2, CASP3), proliferasyon belirteci CCND1’in, östrojen reseptör geni ESR1’in ve tümör baskılayıcı PTEN’in mRNA ekspresyon düzeyleri qRT-PCR yöntemi kullanılarak kantitatif olarak belirlenmiştir. Bulgular: Resveratrol uygulaması Ishikawa hücre canlılığında doza ve zamana bağlı, progresif bir azalmaya yol açmıştır. qRT-PCR analizleri, pro-apoptotik BAX ve CASP3 genlerinde artış; anti-apoptotik BCL-2 ve proliferasyonla ilişkili CCND1 genlerinde azalma; ESR1 ekspresyonunda belirgin baskılanma ve PTEN ekspresyonunda doza bağlı artış olduğunu göstermiştir. Artmış BAX/BCL-2 oranı, hücresel dengenin pro-apoptotik yönde değiştiğini göstermektedir. Sonuç: Bu bulgular, resveratrolün pro-apoptotik transkripsiyonel yanıtları desteklediğini ve hücre canlılığını azalttığını; bu etkilerin östrojen reseptörü sinyallemesi ve PTEN ile ilişkili genlerde meydana gelen değişikliklerle ilişkili olabileceğini göstermektedir. Sub-sitotoksik konsantrasyonlarda gözlenen etkiler, resveratrolün ER-pozitif endometriyal kanser modellerinde deneysel adjuvan tedavi için umut verici bir aday olabileceğini düşündürmektedir.

Anahtar Kelimeler

• Endometriyal kanser
• Resveratrol
• Apoptoz
• Hücre proliferasyonu
• Östrojen reseptörü.

Kaynakça

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