TY  - JOUR
T1  - Caffeine May Improve the Chemotherapeutic Effect of Docetaxel by Inducing UPR and Autophagy in Breast Cancer Cells
TT  - Kafein, Meme Kanseri Hücrelerinde UPR ve Otofajiyi İndükleyerek Dosetakselin Kemoterapötik Etkisini Artırabilir
AU  - Erzurumlu, Yalçın
AU  - Çataklı, Deniz
AU  - Doğan, Hatice Kübra
AU  - Aydoğdu, Esra
PY  - 2023
DA  - March
DO  - 10.55262/fabadeczacilik.1164699
JF  - Fabad Eczacılık Bilimler Dergisi
JO  - Fabad J Pharm Sci
PB  - FABAD Ankara Eczacılık Bilimleri Derneği
WT  - DergiPark
SN  - 1300-4182
SP  - 91
EP  - 104
VL  - 48
IS  - 1
LA  - en
AB  - 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.
KW  - Autophagy
KW  - Apoptosis
KW  - Breast cancer
KW  - Caffeine
KW  - Unfolded Protein Response
KW  - Docetaxel
N2  - 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.
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UR  - https://doi.org/10.55262/fabadeczacilik.1164699
L1  - https://dergipark.org.tr/tr/download/article-file/2606994
ER  -