In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells
Yıl: 2023 Cilt: 48 Sayı: 3 Sayfa Aralığı: 513 - 522 Metin Dili: İngilizce DOI: 10.55262/fabadeczacilik.1351725 İndeks Tarihi: 04-12-2023
In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells
Öz: Pancreatic adenocarcinoma is an aggressive and fatal malignancy due to the lack of early diagnosis and poor therapeutic response. At this point, determining the anticancer potential of non-toxic natural compounds is essential. Caffeic acid phenethyl ester is a bioactive compound with different activities. In this study, the toxicity of caffeic acid phenethyl ester was estimated by in silico methods in 14 pancreatic cancer cells, and its anticancer activity was evaluated in rat adenocarcinoma cells. According to the in silico results, caffeic acid phenethyl ester had anticancer properties without causing severe toxicity. Subsequently, we investigated the effects of caffeic acid phenethyl ester on rat pancreatic cancer (ASML) cells. Caffeic acid phenethyl ester reduced ASML cell viability by up to 27% in a dose- (5, 10, 20, 40, and 80 μM) and time-dependent (24, 48, and 72 h) manner. In the scratch assay, only 80 μM caffeic acid phenethyl ester statistically considerably inhibited ASML cell migration at 24 h. On the other hand, at 48 hours, all doses of caffeic acid phenethyl ester statistically remarkably decreased cell migration. Caffeic acid phenethyl ester also decreased ASML colony numbers at 5 μM and 10 μM compared to the control and completely suppressed colony formation at ≥ 20 μM. Our results revealed that caffeic acid phenethyl ester showed anticancer potential against human and mouse pancreatic cancer cells in silico and significantly inhibited the viability, migration, and colony formation of ASML cells in vitro.
Anahtar Kelime: Kafeik Asit Fenetil Ester’in Pankreas Adenokarsinom Hücreleri Üzerine In Silico ve In Vitro Antikanser Etkileri
Öz: Pankreas adenokarsinomu erken tanı eksikliği ve tedaviye verilen zayıf yanıt nedeniyle agresif ve ölümcül bir malignitedir. Bu noktada toksik olmayan doğal bileşiklerin antikanser potansiyelinin belirlenmesi önem taşımaktadır. Kafeik asit fenetil ester, farklı aktivitelere sahip biyoaktif bir bileşiktir. Bu çalışmada kafeik asit fenetil esterin toksisitesi in siliko yöntemlerle 14 pankreas adenokarsinomu hücresinde tahmin edildi ve antikanser aktivitesi sıçan adenokarsinom hücrelerinde değerlendirildi. İn siliko sonuçlara göre kafeik asit fenetil ester, tehlikeli toksisiteye neden olmadan antikanser özelliklere sahipti. Daha sonra kafeik asit fenetil esterinin sıçan pankreas kanser (ASML) hücreleri üzerindeki etkilerini araştırdık. Kafeik asit fenetil ester, ASML hücre canlılığını doz (5, 10, 20, 40 ve 80 μM) ve zamana bağlı (24, 48 ve 72 saat) bir şekilde %27’ye kadar azalttı. Yara iyileşme deneyinde yalnızca 80 μM kafeik asit fenetil ester, 24 saatte ASML hücre göçünü istatistiksel olarak anlamlı düzeyde inhibe etti. Öte yandan hücre migrasyonu 48. saatte tüm kafeik asit fenetil ester dozlarında istatistiksel olarak anlamlı düzeyde inhibe edildi. Kafeik asit fenetil ester ayrıca kontrole kıyasla 5 μM ve 10 μM dozlarda ASML koloni sayısını azalttı ve ≥ 20 μM dozda koloni oluşumunu tamamen bastırdı. Sonuçlarımız, kafeik asit fenetil esterin in siliko olarak insan ve fare pankreas kanseri hücrelerine karşı antikanser potansiyel gösterdiğini ve in vitro olarak da ASML hücrelerinin canlılığını, hücre göçünü ve koloni oluşumunu önemli ölçüde inhibe ettiğini ortaya çıkardı.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- Avcı, C. B., Gündüz, C., Baran, Y., Sahin, F., Yılmaz, S., Dogan, Z. O., & Saydam, G. (2011). Caffeic acid phenethyl ester triggers apoptosis through induction of loss of mitochondrial membrane potential in CCRF-CEM cells. Journal of cancer research and clinical oncology, 137(1), 41–47. https://doi.org/10.1007/s00432-010-0857-0
- Banerjee, P., Eckert, A. O., Schrey, A. K., & Preissner, R. (2018). ProTox-II: a web server for the prediction of toxicity of chemicals. Nucleic acids research, 46(W1), W257–W263. https://doi.org/10.1093/ nar/gky318
- Chen, M. F., Wu, C. T., Chen, Y. J., Keng, P. C., & Chen, W. C. (2004). Cell killing and radiosensitization by caffeic acid phenethyl ester (CAPE) in lung cancer cells. Journal of radiation research, 45(2), 253– 260. https://doi.org/10.1269/jrr.45.253
- Chen, M. J., Chang, W. H., Lin, C. C., Liu, C. Y., Wang, T. E., Chu, C. H., Shih, S. C., & Chen, Y. J. (2008). Caffeic acid phenethyl ester induces apoptosis of human pancreatic cancer cells involving caspase and mitochondrial dysfunction. Pancreatology : official journal of the International Association of Pancreatology (IAP), 8(6), 566–576. https://doi. org/10.1159/000159843
- Chiang, E. P., Tsai, S. Y., Kuo, Y. H., Pai, M. H., Chiu, H. L., Rodriguez, R. L., & Tang, F. Y. (2014). Caffeic acid derivatives inhibit the growth of colon cancer: involvement of the PI3-K/Akt and AMPK signaling pathways. PloS one, 9(6), e99631. https:// doi.org/10.1371/journal.pone.0099631
- Duan, J., Xiaokaiti, Y., Fan, S., Pan, Y., Li, X., & Li, X. (2017). Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells. Oncology reports, 37(5), 3019–3025. https:// doi.org/10.3892/or.2017.5516
- Eyol, E., Tosun, E., Karakuş, F., Adwan, H., Yılmaz, K., Kovacheva, M., Zepp, M., Berger, MR. (2019). Antineoplastic activity of cucurbitacin I in CC531 rat colorectal cancer cells. Clinical Oncology and Research, 2613-4942. https://doi.org/10.31487/j. COR.2019.01.105
- Filimonov, D.A., Lagunin, A.A., Gloriozova, T.A., Rudik, A.V., Druzhilovskii, D.S., Pogodin, P.V., Poroikov, V.V. (2014). Prediction of the Biological Activity Spectra of Organic Compounds Using the Pass Online Web Resource. Chemistry of Heterocyclic Compounds, 50, 444–457. https://doi. org/10.1007/s10593-014-1496-1
- Franken, N. A., Rodermond, H. M., Stap, J., Haveman, J., & van Bree, C. (2006). Clonogenic assay of cells in vitro. Nature protocols, 1(5), 2315–2319. https:// doi.org/10.1038/nprot.2006.339
- Fu, Y. K., Wang, B. J., Tseng, J. C., Huang, S. H., Lin, C. Y., Kuo, Y. Y., Hour, T. C., & Chuu, C. P. (2022). Combination treatment of docetaxel with caffeic acid phenethyl ester suppresses the survival and the proliferation of docetaxel-resistant prostate cancer cells via induction of apoptosis and metabolism interference. Journal of biomedical science, 29(1), 16. https://doi.org/10.1186/s12929- 022-00797-z
- Hung, M. W., Shiao, M. S., Tsai, L. C., Chang, G. G., & Chang, T. C. (2003). Apoptotic effect of caffeic acid phenethyl ester and its ester and amide analogues in human cervical cancer ME180 cells. Anticancer research, 23(6C), 4773–4780.
- Karakuş, F., Eyol, E., Yılmaz, K., & Ünüvar, S. (2018). Inhibition of cell proliferation, migration and colony formation of LS174T Cells by carbonic anhydrase inhibitor. African health sciences, 18(4), 1303–1310. https://doi.org/10.4314/ahs.v18i4.51
- Karakuş, F., Yılmaz, K., Eyol, E., & Ünüvar, S. (2019). Combination of 2 Bioactive Compounds for Treatment of Breast Cancer: Triterpenoid Cucurbitacin I and Phenolic CAPE. Natural Product Communications, 14(6), https://doi. org/10.1177/1934578X19857492
- Kumar, R., Chaudhary, K., Singla, D., Gautam, A., & Raghava, G. P. (2014). Designing of promiscuous inhibitors against pancreatic cancer cell lines. Scientific reports, 4, 4668. https://doi.org/10.1038/ srep04668
- Liang, C. C., Park, A. Y., & Guan, J. L. (2007). In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nature protocols, 2(2), 329–333. https://doi. org/10.1038/nprot.2007.30
- Lin, Y. H., Chiu, J. H., Tseng, W. S., Wong, T. T., Chiou, S. H., & Yen, S. H. (2006). Antiproliferation and radiosensitization of caffeic acid phenethyl ester on human medulloblastoma cells. Cancer chemotherapy and pharmacology, 57(4), 525–532. https://doi.org/10.1007/s00280-005-0066-8
- Marin, E. H., Paek, H., Li, M., Ban, Y., Karaga, M. K., Shashidharamurthy, R., & Wang, X. (2019). Caffeic acid phenethyl ester exerts apoptotic and oxidative stress on human multiple myeloma cells. Investigational new drugs, 37(5), 837–848. https:// doi.org/10.1007/s10637-018-0701-y
- Mosmann T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of immunological methods, 65(1-2), 55–63. https:// doi.org/10.1016/0022-1759(83)90303-4
- Orth, M., Metzger, P., Gerum, S., Mayerle, J., Schneider, G., Belka, C., Schnurr, M., & Lauber, K. (2019). Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches. Radiation oncology (London, England), 14(1), 141. https://doi.org/10.1186/s13014-019-1345-6
- Papademetrio, D. L., Lompardía, S. L., Simunovich, T., Costantino, S., Mihalez, C. Y., Cavaliere, V., & Álvarez, É. (2016). Inhibition of Survival Pathways MAPK and NF-kB Triggers Apoptosis in Pancreatic Ductal Adenocarcinoma Cells via Suppression of Autophagy. Targeted oncology, 11(2), 183–195. https://doi.org/10.1007/s11523- 015-0388-3
- Prasad, R., & Katiyar, S. K. (2013). Grape seed proanthocyanidins inhibit migration potential of pancreatic cancer cells by promoting mesenchymal-to-epithelial transition and targeting NF-κB. Cancer letters, 334(1), 118–126. https://doi.org/10.1016/j.canlet.2012.08.003
- Sarantis, P., Koustas, E., Papadimitropoulou, A., Papavassiliou, A. G., & Karamouzis, M. V. (2020). Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy. World journal of gastrointestinal oncology, 12(2), 173–181. https://doi.org/10.4251/ wjgo.v12.i2.173
- Tang, H., Yao, X., Yao, C., Zhao, X., Zuo, H., & Li, Z. (2017). Anti-colon cancer effect of caffeic acid p-nitro-phenethyl ester in vitro and in vivo and detection of its metabolites. Scientific reports, 7(1), 7599. https://doi.org/10.1038/s41598-017-07953-8
- Xiong, G., Wu, Z., Yi, J., Fu, L., Yang, Z., Hsieh, C., Yin, M., Zeng, X., Wu, C., Lu, A., Chen, X., Hou, T., & Cao, D. (2021). ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic acids research, 49(W1), W5–W14. https://doi. org/10.1093/nar/gkab255
- Yu, H. J., Shin, J. A., & Cho, S. D. (2023). Inhibition of focal adhesion kinase/paxillin axis by caffeic acid phenethyl ester restrains aggressive behaviors of head and neck squamous cell carcinoma in vitro. Archives of oral biology, 146, 105611. https://doi. org/10.1016/j.archoralbio.2022.105611
- Yu, H. J., Shin, J. A., Yang, I. H., Won, D. H., Ahn, C. H., Kwon, H. J., Lee, J. S., Cho, N. P., Kim, E. C., Yoon, H. J., Lee, J. I., Hong, S. D., & Cho, S. D. (2017). Apoptosis induced by caffeic acid phenethyl ester in human oral cancer cell lines: Involvement of Puma and Bax activation. Archives of oral biology, 84, 94–99. https://doi.org/10.1016/j. archoralbio.2017.09.024
| APA | Tanrıverdi z, Kuzu B, Eyol E, KARAKUŞ F (2023). In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. , 513 - 522. 10.55262/fabadeczacilik.1351725 |
| Chicago | Tanrıverdi zübeyde,Kuzu Burak,Eyol Ergül,KARAKUŞ FUAT In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. (2023): 513 - 522. 10.55262/fabadeczacilik.1351725 |
| MLA | Tanrıverdi zübeyde,Kuzu Burak,Eyol Ergül,KARAKUŞ FUAT In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. , 2023, ss.513 - 522. 10.55262/fabadeczacilik.1351725 |
| AMA | Tanrıverdi z,Kuzu B,Eyol E,KARAKUŞ F In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. . 2023; 513 - 522. 10.55262/fabadeczacilik.1351725 |
| Vancouver | Tanrıverdi z,Kuzu B,Eyol E,KARAKUŞ F In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. . 2023; 513 - 522. 10.55262/fabadeczacilik.1351725 |
| IEEE | Tanrıverdi z,Kuzu B,Eyol E,KARAKUŞ F "In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells." , ss.513 - 522, 2023. 10.55262/fabadeczacilik.1351725 |
| ISNAD | Tanrıverdi, zübeyde vd. "In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells". (2023), 513-522. https://doi.org/10.55262/fabadeczacilik.1351725 |
| APA | Tanrıverdi z, Kuzu B, Eyol E, KARAKUŞ F (2023). In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. FABAD Journal of Pharmaceutical Sciences, 48(3), 513 - 522. 10.55262/fabadeczacilik.1351725 |
| Chicago | Tanrıverdi zübeyde,Kuzu Burak,Eyol Ergül,KARAKUŞ FUAT In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. FABAD Journal of Pharmaceutical Sciences 48, no.3 (2023): 513 - 522. 10.55262/fabadeczacilik.1351725 |
| MLA | Tanrıverdi zübeyde,Kuzu Burak,Eyol Ergül,KARAKUŞ FUAT In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. FABAD Journal of Pharmaceutical Sciences, vol.48, no.3, 2023, ss.513 - 522. 10.55262/fabadeczacilik.1351725 |
| AMA | Tanrıverdi z,Kuzu B,Eyol E,KARAKUŞ F In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. FABAD Journal of Pharmaceutical Sciences. 2023; 48(3): 513 - 522. 10.55262/fabadeczacilik.1351725 |
| Vancouver | Tanrıverdi z,Kuzu B,Eyol E,KARAKUŞ F In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells. FABAD Journal of Pharmaceutical Sciences. 2023; 48(3): 513 - 522. 10.55262/fabadeczacilik.1351725 |
| IEEE | Tanrıverdi z,Kuzu B,Eyol E,KARAKUŞ F "In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells." FABAD Journal of Pharmaceutical Sciences, 48, ss.513 - 522, 2023. 10.55262/fabadeczacilik.1351725 |
| ISNAD | Tanrıverdi, zübeyde vd. "In Silico and In Vitro Anticancer Effects of Caffeic Acid Phenethyl Ester on Pancreatic Adenocarcinoma Cells". FABAD Journal of Pharmaceutical Sciences 48/3 (2023), 513-522. https://doi.org/10.55262/fabadeczacilik.1351725 |
