Caffeine May Improve the Chemotherapeutic Effect of Docetaxel by Inducing UPR and Autophagy in Breast Cancer Cells

Yıl 2023, Cilt: 48 Sayı: 1, 91 - 104, 01.03.2023

Yalçın Erzurumlu , Deniz Çataklı , Hatice Kübra Doğan , Esra Aydoğdu

https://doi.org/10.55262/fabadeczacilik.1164699

Öz

Breast cancer is the most frequently diagnosed cancer type among women. Chemotherapeutics are widely used for breast cancer treatment but acquired drug resistance is the main reason that limits their efficacy. Therefore, there is a continuing need for more effective treatment approaches with fewer side effects. One of the naturally occurring xanthine in coffee beans, caffeine is the most commonly used psychoactive substance worldwide. Numerous studies have drawn attention to the health benefits of coffee intake including decrement in risk of heart disease and risk of some cancers. Docetaxel is a second-generation antineoplastic agent of the taxane family and is widely used in the treatment of numerous cancers such as breast cancer. Herein, we evaluate the effect of caffeine and its combination with docetaxel on MCF-7 breast cancer cells. To test the effect of caffeine and its combination with docetaxel, we evaluate the autophagy, ubiquitin-proteasome system, unfolded protein response signaling and apoptosis-related protein levels were examined by immunoblotting. Cell viability was measured by WST-1 method. Morphological alterations in cells were evaluated in microscopical examinations. We found that caffeine remarkably induced UPR signaling, accelerated autophagic flux, and UPS-dependent protein turnover. Co-administration of caffeine and docetaxel strongly diminished the viability of MCF-7 cells by expanding the cytotoxic effect of docetaxel through accelerating the UPS-dependent protein turnover, induction of autophagy and apoptotic protein levels in a manner dose-dependently. Our results suggest that caffeine supplementation with docetaxel may expand the chemotherapeutic efficiency of docetaxel in breast cancer.

Anahtar Kelimeler

Autophagy, Apoptosis, Breast cancer, Caffeine, Unfolded Protein Response, Docetaxel

Destekleyen Kurum

Suleyman Demirel University

Proje Numarası

TSG-2021-8302, TAB-2020-8253

Teşekkür

We thank Suleyman Demirel University-Innovative Technologies Application and Research Center. We apologize that we could not perform comprehensive reference representation due to reference limitations.

Kafein, Meme Kanseri Hücrelerinde UPR ve Otofajiyi İndükleyerek Dosetakselin Kemoterapötik Etkisini Artırabilir

Öz

Meme kanseri, kadınlar arasında en sık teşhis edilen kanser türüdür. Kemoterapötikler meme kanseri tedavisinde yaygın olarak kullanılmaktadır, ancak kazanılmış ilaç direnci etkinliklerini sınırlayan ana nedendir. Bu nedenle, daha az yan etki ile daha etkili tedavi yaklaşımlarına ihtiyaç vardır. Kahve çekirdeklerinde doğal olarak bulunan ksantinlerden biri olan kafein, dünya çapında en yaygın kullanılan psikoaktif maddedir. Çok sayıda çalışma, kalp hastalığı riskinde azalma ve bazı kanser riskleri de dahil olmak üzere kahve alımının sağlık yararlarına dikkat çekmiştir. Dosetaksel, taksan ailesinden ikinci nesil bir antineoplastik ajandır ve meme kanseri gibi çok sayıda kanserin tedavisinde yaygın olarak kullanılmaktadır. Burada kafeinin ve dosetaksel ile kombinasyonunun MCF-7 meme kanseri hücreleri üzerindeki etkisini değerlendirdik. Kafeinin ve dosetaksel ile kombinasyonunun etkisini test etmek için otofaji, ubikitin-proteazom sistemi, katlanmamış protein yanıt sinyali ve apoptozla ilgili protein seviyelerini immünoblotlama ile inceledik. Hücre canlılığı WST-1 yöntemi ile ölçüldü. Hücrelerdeki morfolojik değişiklikler mikroskopi ile değerlendirildi. Kafeinin dikkat çekici bir şekilde UPR sinyalini uyardığı, otofajik akışı hızlandırdığı ve UPS'ye bağlı protein dönüşümünü uyardığını belirledik. Kafein ve dosetaksel birlikte uygulanması, dosetaksel'in sitotoksik etkisini UPS'ye protein işlenmesini hızlandırarak, otofajiyi uyararak ve apoptotik protein seviyelerini doza bağımlı bir şekilde arttırarak MCF-7 hücrelerinin canlılığını güçlü bir şekilde azalttı. Sonuçlarımız, dosetaksel ile kafein takviyesinin meme kanserinde dosetaksel’in kemoterapötik etkinliğini genişletebileceğini düşündürmektedir.

Anahtar Kelimeler

Otofaji, Apoptozis, Meme Kanseri, Kafein, Katlanmamış Protein Yanıtı, Dosetaksel

Proje Numarası

TSG-2021-8302, TAB-2020-8253

Kaynakça

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