Evaluation of Cytotoxic and Apoptotic Effects of Methotrexate and Carvacrol Combination in Lung Cancer Cancer Cells

Yıl 2025, Cilt: 25 Sayı: 5, 990 - 1000, 01.10.2025

Ayşe Erdoğan

https://doi.org/10.35414/akufemubid.1617388

Öz

Bu çalışmanın amacı, bir kemoterapi ilacı olan metotreksatın (MTX) tek başına ve doğal olarak oluşan bir monoterpenoid fenol olan karvakrol ile birlikte uygulamasının akciğer kanseri hücrelerindeki sitotoksik ve apoptotik etkilerini karşılaştırmaktır. Hücre canlılığı, A-549 hücrelerine MTX tek başına ve karvakrol ile birlikte 48 saat uygulandıktan sonra 3-(4,5-dimetil-2-tiyazolil)-2,5-difenil-2H-tetrazoliumbromid (MTT) testi ile değerlendirilmiştir. Laktat dehidrogenaz (LDH) aktivite testi, MTX tek başına veya karvakrol ile kombinasyon halinde uygulandıktan sonra, A-549 hücrelerinde LDH aktivitesindeki değişiklikler tespit edilerek membran hasarına yol açıp açmadığı değerlendirilmiştir. Hücrelerdeki kaspaz-3 enzim aktivitesindeki değişiklikler, apoptotik etkiyi göstermek için ölçülmüştür. Ayrıca, MTX'in, tek başına ve karvakrol ile birlikte, oksidatif stresin uyarılmasında bir rol oynayıp oynamadığını belirlemek amacıyla glutatyon peroksidaz aktivitesindeki değişiklikler incelenmiştir. Çalışmada, MTX ve karvakrolun kombinasyon halinde 48 saatlik uygulamasının, MTX tek başına uygulamasından daha fazla hücre proliferasyonunu engellediği ve daha güçlü bir sitotoksik etki gösterdiği gözlemlenmiştir. Ayrıca, bu kombinasyon uygulaması membran hasarının bir göstergesi olan LDH aktivitesinde ve apoptoz yolunda görev alan bir enzim olan kaspaz-3 aktivitesinde daha fazla artışa yol açmıştır. Bu çalışmanın sonuçları, MTX ve karvakrol kombinasyonunun, MTX tek başına ugulamasına göre LDH aktivitesinde ve kaspaz-3 aktivitesinde daha büyük bir artışa neden olarak daha belirgin membran hasarı ve apoptotik etki oluşturduğunu göstermektedir. Bu nedenle, kombinasyon uygulaması akciğer kanserinde MTX ile ilişkili yan etkilerin hafifletilmesi için bir strateji olarak değerlendirilebilir.

Anahtar Kelimeler

Akciğer kanseri , Karvakrol , Metotreksat , Kombine tedavi , Apoptotik etki

Proje Numarası

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Akciğer Kanseri Hücrelerinde Metotreksat ve Karvakrol Kombinasyonunun Sitotoksik ve Apoptotik Etkilerinin Değerlendirilmesi

Öz

The aim of this study is to compare the cytotoxic and apoptotic effects of methotrexate (MTX),one of chemotherapy drug, alone application with the combined application of MTX and carvacrol, a naturally occurring monoterpenoid phenol, in lung cancer cells. Cell viability was assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay after A-549 cells were treated with MTX alone and in combination with carvacrol for 48 h. Lactate dehydrogenase (LDH) activity test was employed to assess whether MTX alone or in combination with carvacrol treatments, induced membrane damage by detecting changes in LDH activity in A-549 cells. Caspase-3 enzyme activity changes in cells were measured to show the apoptotic effect. By examining the alterations in glutathione peroxidase activity, an attempt was made to determine whether MTX, alone and in combination with carvacrol, played a role in inducing oxidative stress. It was observed that the combined application of MTX and carvacrol for 48 h inhibited cell proliferation more than MTX alone treatment, demonstrating a stronger cytotoxic effect. Additionally, it caused a greater increase in LDH activity, a marker of membrane damage, and also led to a higher increase in caspase-3 activity, an enzyme involved in the apoptotic pathway. The results of this study show that the combined application of MTX and carvacrol leads to a greater increase in LDH activity and caspase-3 activity compared to MTX alone treatment, indicating more significant membrane damage and apoptotic effects. Therefore, combined treatment could be considered a strategy for alleviating the side effects associated with MTX in lung cancer.

Anahtar Kelimeler

Lung cancer , Carvacrol , Methotrexate , Combined treatment , Apoptotic effect

Proje Numarası

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Kaynakça

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