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Journals / Fabad Eczacılık Bilimler Dergisi / 2026 / Cilt: 48 Sayı: 1

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

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

Yalçın Erzurumlu(SÜLEYMAN DEMİREL ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ)0000-0001-6835-4436
Deniz Çataklı(SÜLEYMAN DEMİREL ÜNİVERSİTESİ)0000-0001-7327-5396
Hatice Kübra Doğan(SÜLEYMAN DEMİREL ÜNİVERSİTESİ)0000-0002-6061-1300
Esra Aydoğdu(SULEYMAN DEMIREL UNIVERSITY)0000-0003-0666-2067
Pages
91–104
Publication Date
2023-03-01
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Our results suggest that caffeine supplementation with docetaxel may expand the chemotherapeutic efficiency of docetaxel in breast cancer.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Breast cancer is the most frequently diagnosed cancer type among women.
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Key Findings & Data:Herein, we evaluate the effect of caffeine and its combination with docetaxel on MCF-7 breast cancer cells.
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Conclusion & Impact:Our results suggest that caffeine supplementation with docetaxel may expand the chemotherapeutic efficiency of docetaxel in breast cancer.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Otofaji · Apoptozis · Meme Kanseri

Abstract

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.

Özet

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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Cite This Article

Erzurumlu, Y., Çataklı, D., Doğan, H. K., Aydoğdu, E. (2023). Caffeine May Improve the Chemotherapeutic Effect of Docetaxel by Inducing UPR and Autophagy in Breast Cancer Cells. Fabad Eczacılık Bilimler Dergisi, Cilt: 48 Sayı: 1, 91–104. https://doi.org/10.55262/fabadeczacilik.1164699

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References (29)

  1. Andersen, L. F., Jacobs, D. R., Jr, Carlsen, M. H., & Blomhoff, R. (2006). Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women’s Health Study. The American Journal of Clinical Nutrition, 83(5), 1039–1046. https://doi.org/10.1093/ajcn/83.5.1039
  2. Campa, C., Doulbeau, S., Dussert, S., Hamon, S., & Noirot, M. (2005). Qualitative relationship between caffeine and chlorogenic acid contents among wild Coffea species. Food Chemistry, 93(1), 135–139. https://doi.org/10.1016/j.foodchem.2004.10.015
  3. Cohen, G. M. (1997). Caspases: the executioners of apoptosis. Biochemical Journal, 326 ( Pt 1), 1–16. https://doi.org/10.1042/bj3260001 Ding, M., Bhupathiraju, S. N., Chen, M., van Dam, R. M., & Hu, F. B. (2014). Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis. Diabetes Care, 37(2), 569–586. https://doi.org/10.2337/dc13-1203
  4. Erzurumlu, Y., & Ballar, P. (2017). Androgen Mediated Regulation of Endoplasmic Reticulum-Associated Degradation and its Effects on Prostate Cancer. Scientific Reports, 7, 40719. https://doi.org/10.1038/srep40719
  5. Gao, W., Wang, X., Zhou, Y., Wang, X., & Yu, Y. (2022). Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy. Signal Transduction and Targeted Therapy, 7(1), 196. https://doi.org/10.1038/s41392-022-01046-3
  6. Glick, D., Barth, S., & Macleod, K. F. (2010). Autophagy: cellular and molecular mechanisms. The Journal of Pathology, 221(1), 3–12. https://doi.org/10.1002/path.2697
  7. Hikita, K., Honda, M., Shimizu, R., Teraoka, S., Kawamoto, B., Yumioka, T., Tsounapi, P., Iwamoto, H., Morizane, S., & Takenaka, A. (2021). Efficacy of Combination Chemotherapy With Docetaxel, Estramustine and Carboplatin in Men With Castration-resistant Prostate Cancer. Cancer Diagnosis & Prognosis, 1(5), 451–457. https://doi.org/10.21873/cdp.100607
  8. Jacobson, K. A., Kirk, K. L., Padgett, W. L., & Daly, J. W. (1985). Functionalized congeners of 1,3-dialkylxanthines: preparation of analogues with high affinity for adenosine receptors. Journal of Medicinal Chemistry, 28(9), 1334–1340. https://doi.org/10.1021/jm00147a038
  9. Jordan, M. A., & Wilson, L. (2004). Microtubules as a target for anticancer drugs. Nature Reviews. Cancer, 4(4), 253–265. https://doi.org/10.1038/nrc1317
  10. Kroemer, G., & Levine, B. (2008). Autophagic cell death: the story of a misnomer. Nature Reviews. Molecular Cell Biology, 9(12), 1004–1010. https://doi.org/10.1038/nrm2529
  11. Lazebnik, Y. A., Kaufmann, S. H., Desnoyers, S., Poirier, G. G., & Earnshaw, W. C. (1994). Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature, 371(6495), 346–347. https://doi.org/10.1038/371346a0
  12. Liu, X., Kim, C. N., Yang, J., Jemmerson, R., & Wang, X. (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell, 86(1), 147–157. https://doi.org/10.1016/s0092-8674(00)80085-9
  13. Lopez-Garcia, E., van Dam, R. M., Willett, W. C., Rimm, E. B., Manson, J. E., Stampfer, M. J., Rexrode, K. M., & Hu, F. B. (2006). Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation, 113(17), 2045–2053. https://doi.org/10.1161/CIRCULATIONAHA.105.598664
  14. Lyseng-Williamson, K. A., & Fenton, C. (2005). Docetaxel: a review of its use in metastatic breast cancer. Drugs, 65(17), 2513–2531. https://doi.org/10.2165/00003495-200565170-00007
  15. Madden, E., Logue, S. E., Healy, S. J., Manie, S., & Samali, A. (2019). The role of the unfolded protein response in cancer progression: From oncogenesis to chemoresistance. Biology of the Cell / under the Auspices of the European Cell Biology Organization, 111(1), 1–17. https://doi.org/10.1111/boc.201800050
  16. Malsy, M., Bitzinger, D., Graf, B., & Bundscherer, A. (2019). Staurosporine induces apoptosis in pancreatic carcinoma cells PaTu 8988t and Panc-1 via the intrinsic signaling pathway. European Journal of Medical Research, 24(1), 5. https://doi.org/10.1186/s40001-019-0365-x
  17. Mata-Cantero, L., Lobato-Gil, S., Aillet, F., Lang, V., & Rodriguez, M. S. (2015). The Ubiquitin-Proteasome System (UPS) as a Cancer Drug Target: Emerging Mechanisms and Therapeutics. In G. T. Wondrak (Ed.), Stress Response Pathways in Cancer: From Molecular Targets to Novel Therapeutics (pp. 225–264). Springer Netherlands. https://doi.org/10.1007/978-94-017-9421-3_11
  18. Mhaidat, N. M., Alzoubi, K. H., Al-Azzam, S. I., & Alsaad, A. A. (2014). Caffeine inhibits paclitaxel induced apoptosis in colorectal cancer cells through the upregulation of Mcl 1 levels. Molecular Medicine Reports, 9(1), 243–248. https://doi.org/10.3892/mmr.2013.1763
  19. Mitchell, D. C., Hockenberry, J., Teplansky, R., & Hartman, T. J. (2015). Assessing dietary exposure to caffeine from beverages in the U.S. population using brand-specific versus category-specific caffeine values. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association, 80, 247–252. https://doi.org/10.1016/j.fct.2015.03.024
  20. Palmeri, L., Vaglica, M., & Palmeri, S. (2008). Weekly docetaxel in the treatment of metastatic breast cancer. Therapeutics and Clinical Risk Management, 4(5), 1047–1059. https://doi.org/10.2147/tcrm.s3397
  21. Pranata, R., Feraldho, A., Lim, M. A., Henrina, J., Vania, R., Golden, N., & July, J. (2022). Coffee and tea consumption and the risk of glioma: a systematic review and dose-response meta-analysis. The British Journal of Nutrition, 127(1), 78–86. https://doi.org/10.1017/S0007114521000830
  22. Prat, A., Pineda, E., Adamo, B., Galván, P., Fernández, A., Gaba, L., Díez, M., Viladot, M., Arance, A., & Muñoz, M. (2015). Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast, 24 Suppl 2, S26–S35. https://doi.org/10.1016/j.breast.2015.07.008
  23. Tomita, K., & Tsuchiya, H. (1989). Caffeine enhancement of the effect of anticancer agents on human sarcoma cells. Japanese Journal of Cancer Research: Gann, 80(1), 83–88. https://doi.org/10.1111/j.1349-7006.1989.tb02249
  24. Trayes, K. P., & Cokenakes, S. E. H. (2021). Breast Cancer Treatment. American Family Physician, 104(2), 171–178.
  25. Wang, A., Wang, S., Zhu, C., Huang, H., Wu, L., Wan, X., Yang, X., Zhang, H., Miao, R., He, L., Sang, X., & Zhao, H. (2016). Coffee and cancer risk: A meta-analysis of prospective observational studies. Scientific Reports, 6, 33711. https://doi.org/10.1038/srep33711
  26. Wang, Z., Gu, C., Wang, X., Lang, Y., Wu, Y., Wu, X., Zhu, X., Wang, K., & Yang, H. (2019). Caffeine enhances the anti-tumor effect of 5-fluorouracil via increasing the production of reactive oxygen species in hepatocellular carcinoma. Medical Oncology, 36(12), 97. https://doi.org/10.1007/s12032-019-1323-8
  27. Yamamoto, N., & Tsuchiya, H. (2011). Clinical Observations of Caffeine-Potentiated Chemotherapy. Journal of Caffeine Research, 1(3), 163–168. https://doi.org/10.1089/jcr.2011.0007
  28. Yoshii, S. R., & Mizushima, N. (2017). Monitoring and Measuring Autophagy. International Journal of Molecular Sciences, 18(9). https://doi.org/10.3390/ijms18091865
  29. Prat, A., Pineda, E., Adamo, B., Galván, P., Fernández, A., Gaba, L., Díez, M., Viladot, M., Arance, A., & Muñoz, M. (2015). Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast, 24 Suppl 2, S26–S35. https://doi.org/10.1016/j.breast.2015.07.008