Safranal'ın Servikal Kanseri C-4 I Hücre Hattı Üzerindeki Antiproliferatif Etkisinin Değerlendirilmesi
Year 2023,
, 117 - 128, 31.10.2023
Souandaou Athoumanı Alı
,
Fatma Gül Özcan
,
Omur Karabulut-bulan
Abstract
Amaç: Safranal, Crocus sativus’un aroma özelliğinden sorumlu bioaktif bir bileşendir. Safranalın antiinflamatuar etkisi dahil olmak üzere farmakolojik özelliklerinin yanı sıra antioksidan aktivitesi birçok çalışmada gösterilmiştir. Çalışmamızda, safranalın serviks karsınoma kökenli C-4 I hücre hattı üzerindeki sitotoksik etkilerini tespit etmek amaçlanmıştır.
Yöntem: Safranalın C-4 I hücre hattı üzerindeki sitotoksik etkisini belirlemek için hücreler belirli sürelerde (2-72 saat) ve konsantrasyonlarda (25-800μM) inkübe edildi. İnkübasyon süresi bitiminde hücrelerin viabilitesi ve safranal antiproliferatif etkisi sırasıyla Mitokondriyal Dehidrojenaz ve Laktat dehidrojenaz enzimlerinin aktiviteleri ile belirlendi. Bununla birlikte, inkübasyon süresince meydana gelen morfolojik değişiklikler Faz kontrast ve ışık mikroskopları aracılığıyla Giemsa boyama kullanılarak gözlemlendi.
Bulgular: elde edilen sonuçlara göre, safranal ile tedavi edilen hücreler kontrol grubu ile karşılaştırıldığında hücrelerin canlılık yüzdesi doza ve inkübasyon süresine bağlı olarak azaldı ve safranal C-4 I hücrelerinin çoğalmasını anlamlı bir şekilde inhibe etti (p<0.05). Nükleer yoğunlaşma, apoptotik ve piknotik hücreler gibi bazı morfolojik değişiklikler ışık mikroskobu altında Giemsa boyama ile incelendi.
Sonuçlar: Elde edilen bulgulara dayanarak safranalın serviks kanseri kökenli C-4 I hücre hatlarına karşı antiproliferatif bir etkiye sahip olduğu söylenebilmektedir.
Anahtar Kelimeler: C-4 I, Safranal, Serviks karsinoma, Sitotoksisite, Antiproliferatif
References
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- Chaiboonchoe, A., Khraiwesh, B., Murali, C., Baig, B., Tarazi, H., Alzahmi, A., Nelson, D. R., Greish, Y. E., Ramadan, W., & Amin, A. (2018). Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells. Scientific Reports, 8(1), 1-15. https://doi.org/10.1038/s41598-018-34855-0
- Cheriyamundath, S., Choudhary, S., & Lopus, M. (2017). Safranal Inhibits HeLa Cell Viability by Perturbing the Reassembly Potential of Microtubules. Phytotherapy Research, 32(1), 170-173. https://doi.org/10.1002/ptr.5938
- Chermahini, S.H., Majid, F.A.A., Sarmidi, M.R., Taghizadeh, E., Salehnezhad, S., 2010, Impact of saffron as an anti-cancer and anti-tumor herb, African Journal of Pharmacy and Pharmacology, 4(11), 834-840. https://doi.org/10.5897/AJPP.9000175
- Erkekoğlu, P., & Baydar, T., (2021). Current in vitro cytotoxicity tests Güncel In Vitro Sitotoksisite Testleri. Hacettepe University Journal of the Faculty of Pharmacy , vol.41, no.1, 45-63.
- Esmaeilzadeh, D., Moodi Ghalibaf, A., Shariati Rad, M., Rezaee, R., Razavi, B. M., & Hosseinzadeh, H. (2023). Pharmacological effects of Safranal: An updated review. Iranian Journal of Basic Medical Sciences, 26(10), 1131-1143. doi: 10.22038/ijbms.2023.69824.15197
- Gavas, S., Quazi, S., & Karpiński, T. M. (2021). Nanoparticles for Cancer Therapy: Current Progress and Challenges. Nanoscale Research Letters, 16. https://doi.org/10.1186/s11671-021-03628-6
- González Martín A. (2007). Molecular biology of cervical cancer. Clinical & translational oncology: official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 9(6), 347–354. https://doi.org/10.1007/s12094-007-0066-8
- Greenwell, M., & Rahman, S. M. (2015). Medicinal Plants: Their Use in Anticancer Treatment. International Journal of Pharmaceutical Sciences and Research, 6(10), 4103. https://doi.org/10.13040/IJPSR.0975-8232.6(10).4103-12
- Hatziagapiou, K., Nikola, O., Marka, S., Koniari, E., Kakouri, E., Zografaki, M., Mavrikou, S. S., Kanakis, C., Flemetakis, E., Chrousos, G. P., Kintzios, S., Lambrou, G. I., & Tarantilis, P. A. (2022). An In Vitro Study of Saffron Carotenoids: The Effect of Crocin Extracts and Dimethylcrocetin on Cancer Cell Lines. Antioxidants, 11(6), 1074. https://doi.org/10.3390/antiox11061074
- Hosseinzadeh, H., & Sadeghnia, H. R. (2005). Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, 8(3), 394–399. PubMed. https://pubmed.ncbi.nlm.nih.gov/16401389/
- Jabini, R., Ehtesham-Gharaee, M., Dalirsani, Z., Mosaffa, F., Delavarian, Z., & Behravan, J. (2017). Evaluation of the Cytotoxic Activity of Crocin and Safranal, Constituents of Saffron, in Oral Squamous Cell Carcinoma (KB Cell Line). Nutrition and cancer, 69(6), 911–919. https://doi.org/10.1080/01635581.2017.1339816
- Liontos, M., Kyriazoglou, A., Dimitriadis, I., Dimopoulos, M. A., & Bamias, A. (2019). Systemic therapy in cervical cancer: 30 years in review. Critical reviews in oncology/hematology, 137, 9–17. https://doi.org/10.1016/j.critrevonc.2019.02.009
- Maeda, A., Kai, K., Ishii, M., Ishii, T., & Akagawa, M. (2014). Safranal, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves glucose tolerance in diabetic KK-Ay mice. Molecular Nutrition & Food Research, 58(6), 1177-1189. https://doi.org/10.1002/mnfr.201300675
- Malaekeh-Nikouei, B., Mousavi, S. H., Shahsavand, S., Mehri, S., Nassirli, H., & Moallem, S. A. (2013). Assessment of cytotoxic properties of safranal and nanoliposomal safranal in various cancer cell lines. Phytotherapy research : PTR, 27(12), 1868–1873. https://doi.org/10.1002/ptr.4945
- Milajerdi, A., Djafarian, K., & Hosseini, B. (2016). The toxicity of saffron (Crocus sativus L.) and its constituents against normal and cancer cells. Journal of Nutrition & Intermediary Metabolism, 3, 23-32. https://doi.org/10.1016/j.jnim.2015.12.332
- Mollazadeh, H., Emami, S. A., & Hosseinzadeh, H. (2015). Razi’s Al-Hawi and saffron (Crocus sativus): A review. Iranian Journal of Basic Medical Sciences, 18(12), 1153-1166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744354/
- Moratalla-López, N., Bagur, M. J., Lorenzo, C., Martínez-Navarro, M. E., Salinas, M. R., & Alonso, G. L. (2019). Bioactivity and Bioavailability of the Major Metabolites of Crocus sativus L. Flower. Molecules, 24(15). https://doi.org/10.3390/molecules24152827
- Nanda, S., & Madan, K. (2021). The role of Safranal and saffron stigma extracts in oxidative stress, diseases and photoaging: A systematic review. Heliyon, 7(2), e06117. https://doi.org/10.1016/j.heliyon.2021.e06117
- Ozcan, G., Dagdeviren Ozsoylemez, O., Akman, G., Khalilia, W., Tezel Yetiz, B., Karagoz, A., Melikoglu, G., Anil, S., Kultur, S., & Sutlupinar, N. (2016). Screening for antitumor activity of various plant extracts on HeLa and C 4-I cell lines. Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 21(6), 1552–1560.
- Ozsoylemez, O. D., & Ozcan, G. (2018). The Antiproliferative Activity of Colchicum umbrosum Plant Extract and Paclitaxel on C-4 I and Vero Cells. European Journal of Biology, 77(2), 81-88. https://doi.org/10.26659/EurJBiol.2018.0016
- Rezaee, R., & Hosseinzadeh, H. (2013). Safranal: From an Aromatic Natural Product to a Rewarding Pharmacological Agent. Iranian Journal of Basic Medical Sciences, 16(1), 12-26. doi: 10.22038/ijbms.2013.244
- Samarghandian, S., & Shabestari, M. M. (2013). DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line. Indian Journal of Urology : IJU : Journal of the Urological Society of India, 29(3), 177-183. https://doi.org/10.4103/0970-1591.117278
- Samarghandian, S., & Shabestari, M. M. (2013). DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line. Indian Journal of Urology : IJU : Journal of the Urological Society of India, 29(3), 177-183. https://doi.org/10.4103/0970-1591.117278
- Samarghandian, S., Samini, F., Azimi-Nezhad, M., & Farkhondeh, T. (2017). Anti-oxidative effects of safranal on immobilization-induced oxidative damage in rat brain. Neuroscience letters, 659, 26–32. https://doi.org/10.1016/j.neulet.2017.08.065
- Samarghandian, S., Shoshtari, M. E., Sargolzaei, J., Hossinimoghadam, H., & Farahzad, J. A. (2014). Anti-tumor activity of safranal against neuroblastoma cells. Pharmacognosy Magazine, 10(Suppl 2), S419. https://doi.org/10.4103/0973-1296.133296
- Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA: a cancer journal for clinicians, 70(1), 7–30. https://doi.org/10.3322/caac.21590
- Tokur, O. & Aksoy, A. (2017). In Vitro Sitotoksisite Testleri . Harran Üniversitesi Veteriner Fakültesi Dergisi , 6 (1) , 112-118 . https://doi.org/10.31196/huvfd.325794
- Toledo-Ibelles, P., & Mas-Oliva, J. (2018). Antioxidants in the Fight Against Atherosclerosis: Is This a Dead End?. Current atherosclerosis reports, 20(7), 36. https://doi.org/10.1007/s11883-018-0737-7
- Xu, Q., Yu, J., Jia, G., Li, Z., & Xiong, H. (2022). Crocin attenuates NF-κB-mediated inflammation and proliferation in breast cancer cells by down-regulating PRKCQ. Cytokine, 154, 155888. https://doi.org/10.1016/j.cyto.2022.155888
- Zarrineh, M., Ashrafian, S., Jensen, P., Nawrocki, A., Ansari, A. M., Rezadoost, H., Ghassempour, A., & Larsen, M. R. (2022). Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. Journal of Proteomics, 259, 104539. https://doi.org/10.1016/j.jprot.2022.104539
Evaluation of the Antiproliferative Effect of Safranal in C-4 I Cervical Cancer Cell Line
Year 2023,
, 117 - 128, 31.10.2023
Souandaou Athoumanı Alı
,
Fatma Gül Özcan
,
Omur Karabulut-bulan
Abstract
Aim: Safranal is a bioactive compound responsible for the aroma propriety of Crocus sativus. Many studies have shown the antioxidant activity of safranal besides some pharmacological properties, including its anti-inflammatory effect. Our study aimed on identifying the cytotoxic effects of safranal on the C-4 I cell line of cervical cancer.
Methods: The cytotoxic effect of safranal on the C-4 I cell line was determined after incubating the cells for certain durations (2 to 72 hours) and concentrations (25 to 800 µM). After incubation, cell viability and anti-proliferation effect of safranal were determined respectively by Mitochondrial Dehydrogenase and Lactate dehydrogenase enzymes activities assays. Additionally, morphological changes occurring during incubation in cells were examined with inverted and optical microscope using Giemsa staining.
Results: According to the results, compared to Control group, the % viability of treated cells was decreased depending on concentration and the incubation time, and safranal significantly inhibited the growth of C-4 I cells (p<0.05). Some morphological changes such as nuclear condensation, and apoptotic and pyknotic cells were examined under light microscopy with Giemsa staining.
Conclusion: In conclusion, based on these results safranal has an antiproliferative effect against cervical cancer C-4 I cell lines.
References
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- Burak, A. K. Ç. A., & Güven, L. (2023). Kanser Tedavisinde Kullanılan Tıbbi Bitkiler. Sağlık Bilimlerinde Öncü Ve Çağdaş Çalışmalar, 641-679. https://scholar.google.com/citations?view_op=view_citation&hl=tr&user=pHHgdH8AAAAJ&citation_for_view=pHHgdH8AAAAJ:MXK_kJrjxJIC
- Cerdá-Bernad, D., Valero-Cases, E., Pastor, J. J., & Frutos, M. J. (2022). Saffron bioactives crocin, crocetin and safranal: effect on oxidative stress and mechanisms of action. Critical reviews in food science and nutrition, 62(12), 3232–3249. https://doi.org/10.1080/10408398.2020.1864279.
- Chaiboonchoe, A., Khraiwesh, B., Murali, C., Baig, B., Tarazi, H., Alzahmi, A., Nelson, D. R., Greish, Y. E., Ramadan, W., & Amin, A. (2018). Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells. Scientific Reports, 8(1), 1-15. https://doi.org/10.1038/s41598-018-34855-0
- Cheriyamundath, S., Choudhary, S., & Lopus, M. (2017). Safranal Inhibits HeLa Cell Viability by Perturbing the Reassembly Potential of Microtubules. Phytotherapy Research, 32(1), 170-173. https://doi.org/10.1002/ptr.5938
- Chermahini, S.H., Majid, F.A.A., Sarmidi, M.R., Taghizadeh, E., Salehnezhad, S., 2010, Impact of saffron as an anti-cancer and anti-tumor herb, African Journal of Pharmacy and Pharmacology, 4(11), 834-840. https://doi.org/10.5897/AJPP.9000175
- Erkekoğlu, P., & Baydar, T., (2021). Current in vitro cytotoxicity tests Güncel In Vitro Sitotoksisite Testleri. Hacettepe University Journal of the Faculty of Pharmacy , vol.41, no.1, 45-63.
- Esmaeilzadeh, D., Moodi Ghalibaf, A., Shariati Rad, M., Rezaee, R., Razavi, B. M., & Hosseinzadeh, H. (2023). Pharmacological effects of Safranal: An updated review. Iranian Journal of Basic Medical Sciences, 26(10), 1131-1143. doi: 10.22038/ijbms.2023.69824.15197
- Gavas, S., Quazi, S., & Karpiński, T. M. (2021). Nanoparticles for Cancer Therapy: Current Progress and Challenges. Nanoscale Research Letters, 16. https://doi.org/10.1186/s11671-021-03628-6
- González Martín A. (2007). Molecular biology of cervical cancer. Clinical & translational oncology: official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 9(6), 347–354. https://doi.org/10.1007/s12094-007-0066-8
- Greenwell, M., & Rahman, S. M. (2015). Medicinal Plants: Their Use in Anticancer Treatment. International Journal of Pharmaceutical Sciences and Research, 6(10), 4103. https://doi.org/10.13040/IJPSR.0975-8232.6(10).4103-12
- Hatziagapiou, K., Nikola, O., Marka, S., Koniari, E., Kakouri, E., Zografaki, M., Mavrikou, S. S., Kanakis, C., Flemetakis, E., Chrousos, G. P., Kintzios, S., Lambrou, G. I., & Tarantilis, P. A. (2022). An In Vitro Study of Saffron Carotenoids: The Effect of Crocin Extracts and Dimethylcrocetin on Cancer Cell Lines. Antioxidants, 11(6), 1074. https://doi.org/10.3390/antiox11061074
- Hosseinzadeh, H., & Sadeghnia, H. R. (2005). Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, 8(3), 394–399. PubMed. https://pubmed.ncbi.nlm.nih.gov/16401389/
- Jabini, R., Ehtesham-Gharaee, M., Dalirsani, Z., Mosaffa, F., Delavarian, Z., & Behravan, J. (2017). Evaluation of the Cytotoxic Activity of Crocin and Safranal, Constituents of Saffron, in Oral Squamous Cell Carcinoma (KB Cell Line). Nutrition and cancer, 69(6), 911–919. https://doi.org/10.1080/01635581.2017.1339816
- Liontos, M., Kyriazoglou, A., Dimitriadis, I., Dimopoulos, M. A., & Bamias, A. (2019). Systemic therapy in cervical cancer: 30 years in review. Critical reviews in oncology/hematology, 137, 9–17. https://doi.org/10.1016/j.critrevonc.2019.02.009
- Maeda, A., Kai, K., Ishii, M., Ishii, T., & Akagawa, M. (2014). Safranal, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves glucose tolerance in diabetic KK-Ay mice. Molecular Nutrition & Food Research, 58(6), 1177-1189. https://doi.org/10.1002/mnfr.201300675
- Malaekeh-Nikouei, B., Mousavi, S. H., Shahsavand, S., Mehri, S., Nassirli, H., & Moallem, S. A. (2013). Assessment of cytotoxic properties of safranal and nanoliposomal safranal in various cancer cell lines. Phytotherapy research : PTR, 27(12), 1868–1873. https://doi.org/10.1002/ptr.4945
- Milajerdi, A., Djafarian, K., & Hosseini, B. (2016). The toxicity of saffron (Crocus sativus L.) and its constituents against normal and cancer cells. Journal of Nutrition & Intermediary Metabolism, 3, 23-32. https://doi.org/10.1016/j.jnim.2015.12.332
- Mollazadeh, H., Emami, S. A., & Hosseinzadeh, H. (2015). Razi’s Al-Hawi and saffron (Crocus sativus): A review. Iranian Journal of Basic Medical Sciences, 18(12), 1153-1166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744354/
- Moratalla-López, N., Bagur, M. J., Lorenzo, C., Martínez-Navarro, M. E., Salinas, M. R., & Alonso, G. L. (2019). Bioactivity and Bioavailability of the Major Metabolites of Crocus sativus L. Flower. Molecules, 24(15). https://doi.org/10.3390/molecules24152827
- Nanda, S., & Madan, K. (2021). The role of Safranal and saffron stigma extracts in oxidative stress, diseases and photoaging: A systematic review. Heliyon, 7(2), e06117. https://doi.org/10.1016/j.heliyon.2021.e06117
- Ozcan, G., Dagdeviren Ozsoylemez, O., Akman, G., Khalilia, W., Tezel Yetiz, B., Karagoz, A., Melikoglu, G., Anil, S., Kultur, S., & Sutlupinar, N. (2016). Screening for antitumor activity of various plant extracts on HeLa and C 4-I cell lines. Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 21(6), 1552–1560.
- Ozsoylemez, O. D., & Ozcan, G. (2018). The Antiproliferative Activity of Colchicum umbrosum Plant Extract and Paclitaxel on C-4 I and Vero Cells. European Journal of Biology, 77(2), 81-88. https://doi.org/10.26659/EurJBiol.2018.0016
- Rezaee, R., & Hosseinzadeh, H. (2013). Safranal: From an Aromatic Natural Product to a Rewarding Pharmacological Agent. Iranian Journal of Basic Medical Sciences, 16(1), 12-26. doi: 10.22038/ijbms.2013.244
- Samarghandian, S., & Shabestari, M. M. (2013). DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line. Indian Journal of Urology : IJU : Journal of the Urological Society of India, 29(3), 177-183. https://doi.org/10.4103/0970-1591.117278
- Samarghandian, S., & Shabestari, M. M. (2013). DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line. Indian Journal of Urology : IJU : Journal of the Urological Society of India, 29(3), 177-183. https://doi.org/10.4103/0970-1591.117278
- Samarghandian, S., Samini, F., Azimi-Nezhad, M., & Farkhondeh, T. (2017). Anti-oxidative effects of safranal on immobilization-induced oxidative damage in rat brain. Neuroscience letters, 659, 26–32. https://doi.org/10.1016/j.neulet.2017.08.065
- Samarghandian, S., Shoshtari, M. E., Sargolzaei, J., Hossinimoghadam, H., & Farahzad, J. A. (2014). Anti-tumor activity of safranal against neuroblastoma cells. Pharmacognosy Magazine, 10(Suppl 2), S419. https://doi.org/10.4103/0973-1296.133296
- Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA: a cancer journal for clinicians, 70(1), 7–30. https://doi.org/10.3322/caac.21590
- Tokur, O. & Aksoy, A. (2017). In Vitro Sitotoksisite Testleri . Harran Üniversitesi Veteriner Fakültesi Dergisi , 6 (1) , 112-118 . https://doi.org/10.31196/huvfd.325794
- Toledo-Ibelles, P., & Mas-Oliva, J. (2018). Antioxidants in the Fight Against Atherosclerosis: Is This a Dead End?. Current atherosclerosis reports, 20(7), 36. https://doi.org/10.1007/s11883-018-0737-7
- Xu, Q., Yu, J., Jia, G., Li, Z., & Xiong, H. (2022). Crocin attenuates NF-κB-mediated inflammation and proliferation in breast cancer cells by down-regulating PRKCQ. Cytokine, 154, 155888. https://doi.org/10.1016/j.cyto.2022.155888
- Zarrineh, M., Ashrafian, S., Jensen, P., Nawrocki, A., Ansari, A. M., Rezadoost, H., Ghassempour, A., & Larsen, M. R. (2022). Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. Journal of Proteomics, 259, 104539. https://doi.org/10.1016/j.jprot.2022.104539