İnsan prostat kanseri hücreleri üzerinde escinin apoptozis ve morfolojik değişiklikleri tetikleyici sitotoksik etkileri
Abstract
Prostat kanseri, dünya çapında % 28'lik bir oranla erkeklerde en sık görülen kanser türlerinden biridir. Bu kanser türü, Türkiye'de erkeklerde görülen kanser vakalarının yaklaşık % 37'sini oluşturmaktadır. Son kanser araştırmaları, kanser tedavisi için potansiyele sahip doğal ajanlara odaklanmıştır. Escin, bu özelliğ,nden dolayı en çok araştırılan ajanlardan biridir, ancak insan prostat kanseri hücresinin morfolojisi üzerindeki etkileri henüz ayrıntılı olarak araştırılmamıştır. Bu nedenle, bu çalışmanın amacı escinin Du-145 insan prostat kanseri hücreleri üzerindeki antiproliferatif, sitotoksik ve proapoptotik etkilerini araştırmaktır. Esinin prostat kanseri hücreleri üzerindeki sitotoksisitesi sulforhodamine B (SRB) testi ile incelenmiştir ve eliza plaka okuyucu (BioTek Synergy HTX) sonuçlarından canlılık yüzdeleri ve IC50 değeri saptanmıştır. Morfolojik değişiklikler için escinin IC50 değeri ile inkübe edilmiş olan Du-145 hücreleri, bir konfokal mikroskop (Leica, TCS SP5 II, Almanya) altında değerlendirilmiştir. Hücrelerin apoptotik profilleri akış sitometrisi ile araştırılmıştır. SRB bulgularına göre escin, prostat kanseri hücrelerinin canlılığını doza bağlı olarak azaltmış ve IC50 değeri 24 saat için 30,48 µM olarak tespit edilmiştir. Konfokal mikroskopi sonuçlarında, escin ile muamele edilmiş hücrelerin morfolojisinde, parçalanmış ve deforme olmuş çekirdekler, kromatin yoğunlaşması, hücre iskeletindeki fragmantasyonlar ve hücre büzüşmesi şeklinde önemli değişiklikler saptanmıştır. Anneksin-V tekniği, Du-145 hücrelerinde escinin apoptotik hücre ölümünü tetiklediğini göstermiştir. Çalışma sonuçlarına bakıldığında, escinin insan prostat kanseri hücrelerinde sitotoksik etki göstererek morfolojik değişikliklere neden olduğu ve apoptozisi indüklediği saptanmıştır.
Keywords
References
- Sirtori, C. R. (2001). Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacol. Res., 44, 183-193. Gallelli, L. (2019). Escin: a review of its anti-edematous, anti-inflammatory, and venotonic properties. Drug. Des. Devel. Ther.,13, 3425-3437.
- Bombardelli, P. M. & Griffini, A. (1996). Aesculus hippocastanum L. Fitoterapia, 67 (6), 483-511.
- Matsuda, H., Li, Y. & Yoshikawa, M. (2000). Possible involvement of 5-HT and 5-HT2 receptors in acceleration of gastrointestinal transit by escin Ib in mice. Life Sci. 66, 2233-2238.
- Satoh, S., Kreutz, R., Wilm, C., Ganten, D. & Pfitzer, G. (1994). Augmented agonist-induced Ca(2þ)-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells. J. Clin. Investig. 94, 1397-1403.
- Facino, R. M., Carini, M., Stefani, R., Aldini G. & Saibene, L. (1995). Anti-elastase and antihyaluronidase activities of saponins and sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: factors contributing to their efficacy in the treatment of venous insufficiency. Arch. Pharmazie 328, 720-724.
- Hu, J. N., Zhu, X. M., Han, L. K., Saito, M., Sun, Y.S., Yoshikawa, M., Kimura, Y. & Zheng, Y. N. (2008). Anti-obesity effects of escins extracted from the seeds of Aesculus turbinata BLUME (Hippocastanaceae). Chem. Pharm. Bull. 56, 12-16.
- Waller, G. R. & Yamasaki, K. (1996). Saponins Used in Traditional and Modern Medicine. 1 ed., Springer, Boston, MA.
- Cheong D. H. J., Arfuso, F. & Sethi, G. (2018). Molecular targets and anti-cancer potential of escin. Cancer Letters 422: 1-8.
- Petrova, S., Yurukova, L. & Velcheva, I. (2012). Horse chestnut (Aesculus hippocastanum L.) as a biomonitor of air pollution in the town of Plovdiv (Bulgaria). J. BioSci. Biotech., 1(3): 241-247.
- Allen, D. J. & Khela, S. (2017). Aesculus hippocastanum. The IUCN Red List of Threatened Species, e.T202914A68084249.
- Snieškienė, V., Baležentienė, L. & Stankevičienė, A. (2011). State of horse-chestnut, Aesculus hippocastanum L., in Lithuania: diseases and pest damages. Ekologija., 57, 62–69.
- Güney, G., Kutlu, H. M. & Iscan, A. (2013). The apoptotic effects of escin in the H-Ras transformed 5RP7 cell line. Phytother Res. 27, 900-905.
- Çiftçi, G. A., Iscan, A. & Kutlu H. M. (2015). Escin reduces cell proliferation and induces apoptosis on glioma and lung adenocarcinoma cell lines. Cytotechnology., 67, 893-904.
- Wang, Y. W., Wang, S. J., Zhou, Y. N., Pan, S. H. & Sun, B. (2012). Escin augments the efficacy of gemcitabine through down-regulation of nuclear factor-kB and nuclear factor-kB-regulated gene products in pancreatic cancer both in vitro and in vivo. J. Canc. Res. Clin. Oncol., 138, 785-797.
- Ming, Z. J., Hu, Y., Qiu, Y. H., Cao, L. & Zhang, X. G. (2010). Synergistic effects of [beta]-aescin and 5-fluorouracil in human hepatocellular carcinoma SMMC-7721 cells. Phytomedicine: Int. J. Phytother. Phytopharm., 17, 575.
- Demain, A. L. & Vaishnav, P. (2011). Natural products for cancer chemotherapy. Microbial. Biotech., 4, 687-699.
- Deorukhkar, A., Krishnan, S., Sethi, G. & Aggarwal, B. B. (2007). Back to basics: how natural products can provide the basis for new therapeutics. Expet. Opin. Invest. Drugs., 16, 1753-1773.
Cytotoxic impacts of escin via inducing apoptosis and morphological changes on human prostate cancer cells
Abstract
Prostate cancer is one of the most prevalent cancer types in males with a percentages of 28% worldwide. This cancer type comprises approximately 37% of the cancer incidences in males in Turkey. Recent cancer investigations are focused on natural agents with good potent for cancer therapy. Escin is one of the most investigated agents of that kind but its effects on human prostate cancer cell’s morphology is not investigated in detail, yet. Thus, the aim of this study is to investigate the antiproliferative, cytotoxic and proapoptotic effects of escin, on prostate cancer cells Du-145. Cytotoxicity of escin on prostate cancer cells was intestigated by using sulforhodamine B (SRB) assay and viability percentages and IC50 value were detected from the elisa reader (BioTek Synergy HTX) results. For morphological changes, Du-145 cells treated with the IC50 value of escin were evaluated under a confocal microscope (Leica, TCS SP5 II, Germany). Apoptosis profiles of cells were investigated by flow cytometry. According to the SRB findings escin reduced the viability of prostate cancer cells in dose-dependent manner and the IC50 value was detected as 30.48 µM for 24 hours. On the confocal microscopy results it was confirmed that escin significantly changed the morphology of the treated cells as disintegrated and deformed nuclei, chromatin condensation, fragmentations in the cytoskeleton also shrinkage of prostate cells. Annexin-V technique indicated the apoptotic cell death trigered by escin in Du-145 cells. Based on the study results, it was concluded that escin changed the morphology of prostate cancer cells and induced apoptosis on prostate cancer cells.
Keywords
References
- Sirtori, C. R. (2001). Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacol. Res., 44, 183-193. Gallelli, L. (2019). Escin: a review of its anti-edematous, anti-inflammatory, and venotonic properties. Drug. Des. Devel. Ther.,13, 3425-3437.
- Bombardelli, P. M. & Griffini, A. (1996). Aesculus hippocastanum L. Fitoterapia, 67 (6), 483-511.
- Matsuda, H., Li, Y. & Yoshikawa, M. (2000). Possible involvement of 5-HT and 5-HT2 receptors in acceleration of gastrointestinal transit by escin Ib in mice. Life Sci. 66, 2233-2238.
- Satoh, S., Kreutz, R., Wilm, C., Ganten, D. & Pfitzer, G. (1994). Augmented agonist-induced Ca(2þ)-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells. J. Clin. Investig. 94, 1397-1403.
- Facino, R. M., Carini, M., Stefani, R., Aldini G. & Saibene, L. (1995). Anti-elastase and antihyaluronidase activities of saponins and sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: factors contributing to their efficacy in the treatment of venous insufficiency. Arch. Pharmazie 328, 720-724.
- Hu, J. N., Zhu, X. M., Han, L. K., Saito, M., Sun, Y.S., Yoshikawa, M., Kimura, Y. & Zheng, Y. N. (2008). Anti-obesity effects of escins extracted from the seeds of Aesculus turbinata BLUME (Hippocastanaceae). Chem. Pharm. Bull. 56, 12-16.
- Waller, G. R. & Yamasaki, K. (1996). Saponins Used in Traditional and Modern Medicine. 1 ed., Springer, Boston, MA.
- Cheong D. H. J., Arfuso, F. & Sethi, G. (2018). Molecular targets and anti-cancer potential of escin. Cancer Letters 422: 1-8.
- Petrova, S., Yurukova, L. & Velcheva, I. (2012). Horse chestnut (Aesculus hippocastanum L.) as a biomonitor of air pollution in the town of Plovdiv (Bulgaria). J. BioSci. Biotech., 1(3): 241-247.
- Allen, D. J. & Khela, S. (2017). Aesculus hippocastanum. The IUCN Red List of Threatened Species, e.T202914A68084249.
- Snieškienė, V., Baležentienė, L. & Stankevičienė, A. (2011). State of horse-chestnut, Aesculus hippocastanum L., in Lithuania: diseases and pest damages. Ekologija., 57, 62–69.
- Güney, G., Kutlu, H. M. & Iscan, A. (2013). The apoptotic effects of escin in the H-Ras transformed 5RP7 cell line. Phytother Res. 27, 900-905.
- Çiftçi, G. A., Iscan, A. & Kutlu H. M. (2015). Escin reduces cell proliferation and induces apoptosis on glioma and lung adenocarcinoma cell lines. Cytotechnology., 67, 893-904.
- Wang, Y. W., Wang, S. J., Zhou, Y. N., Pan, S. H. & Sun, B. (2012). Escin augments the efficacy of gemcitabine through down-regulation of nuclear factor-kB and nuclear factor-kB-regulated gene products in pancreatic cancer both in vitro and in vivo. J. Canc. Res. Clin. Oncol., 138, 785-797.
- Ming, Z. J., Hu, Y., Qiu, Y. H., Cao, L. & Zhang, X. G. (2010). Synergistic effects of [beta]-aescin and 5-fluorouracil in human hepatocellular carcinoma SMMC-7721 cells. Phytomedicine: Int. J. Phytother. Phytopharm., 17, 575.
- Demain, A. L. & Vaishnav, P. (2011). Natural products for cancer chemotherapy. Microbial. Biotech., 4, 687-699.
- Deorukhkar, A., Krishnan, S., Sethi, G. & Aggarwal, B. B. (2007). Back to basics: how natural products can provide the basis for new therapeutics. Expet. Opin. Invest. Drugs., 16, 1753-1773.
Details
| Primary Language | English |
|---|---|
| Subjects | Biochemistry and Cell Biology (Other) |
| Journal Section | Research Article |
| Authors | |
| Publication Date | April 15, 2021 |
| Submission Date | February 28, 2021 |
| Acceptance Date | March 5, 2021 |
| Published in Issue | Year 2021 Volume: 14 Issue: 1 |
Cited By
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