DETERMINATION OF THE ANTIPROLIFERATIVE EFFECT OF STERNBERGIA LUTEA (L.) KER GAWL. EX SPRENG. EXTRACTS ON A375 MALIGNANT MELONOMA CELL LINE
Yıl 2025,
Cilt: 14 Sayı: 1, 25 - 33, 29.01.2025
Zemheri Şaman
,
Sevil Yeniocak
,
İrem Demir
,
Ergun Kaya
,
Nurdan Saraç
Öz
Epidemiological evidence confirms that plants are primary sources of drugs used to reduce the incidence of cancer and prevent cancer-related deaths. Sternbergia species are used for therapeutic purposes due to the amaryllidaceae alkaloids, lectins, phenolic acids, pigments, and volatile components they contain. In this study, the anticancer properties of S. lutea extracts were tested on the A375 malignant melonoma cell line. In addition, in the study, the transcriptional expression of BCL-XL and Cas9 genes, which function in cell proliferation and apoptotic pathways, in cells treated with plant extracts were determined by qRT-PCR. According to the cytotoxicity results made by the MTT test, the highest inhibition percentage was determined at the plant's concentration of 500 μg/𝑚L. At this concentration, A375 cells were inhibited by 83.63%, and the IC50 value of the extract was calculated as 194.64 μg/𝑚L. In addition, in qRT-PCR analyses, a statistically significant increase was observed in the mRNA expression levels of Cas9 genes, which are positively correlated with the apoptotic pathway, in the extract and cisplatin-applied groups compared to the control group.
Kaynakça
- [1] Yuan H, Ma Q, Ye L, Piao G. The Traditional Medicine and Modern Medicine from Natural Products. Molecules (2016); 21(5): 559.
- [2] Thomford NE, Senthebane DA, Rowe A, Munro D, Seele P, Maroyi A, Dzobo K. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery. International Journal of Molecular Sciences 2018; 19(6): 1578.
- [3] Abdul Ghafoor N, Galatali S, Yeniocak S, Kaya E, Sarac N, Ugur A. Investigating anticancer potency of in vitro propagated endemic Thymus cilicicus Boiss. & Bal. extract on human lung, breast, and prostate cancer cell lines. Biologia 2022; 77: 3229-3239.
- [4] Najmi A, Javed SA, Al Bratty M, Alhazmi HA. Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents. Molecules 2022; 27(2): 349.
- [5] Chaachouay N, Zidane L. Plant-Derived Natural Products: A Source for Drug Discovery and Development. Drugs and Drug Candidates 2024; 3(1): 184-207.
- [6] Kaya E, Galatalı S, Güldağ S, Öztürk B, Ceylan M, Çelik O, Aktay İ. Mass production of medicinal plants for obtaining secondary metabolite using liquid mediums via bioreactor systems: SETISTM and RITA®. Turkish Journal of Scientific Reviews 2018; 11(2): 5-10.
- [7] Kivrak S, Göktürk T, Kivrak I, Kaya E, Karababa E. Investigation of phenolic profiles and antioxidant activities of some Salvia species commonly grown in Southwest Anatolia using UPLC-ESI-MS/MS. Food Science and Biotechnology 2019; 39: 423-431.
- [8] Mucha P, Skoczyńska A, Małecka M, Hikisz P, Budzisz E. Overview of the Antioxidant and Anti-Inflammatory Activities of Selected Plant Compounds and Their Metal Ions Complexes. Molecules 2021; 26(16): 4886.
- [9] Yeniocak S, Galatalı S, Demir İ, Uğur A, Saraç N, Kaya E. Investigation of biological activities of in vitro grown Sesamum orientale plant extract on the cell cultures: wound healing and antiproliferation. Advances in Traditional Medicine 2024; 1-14.
- [10] Youssef S, Mahmood A, Vela E. On the genus Sternbergia (Amaryllidaceae) in Iraq. Anales Del Jardín Botánico De Madrid 2017; 74(1): e053.
- [11] Desgagné-Penix I. Biosynthesis of alkaloids in Amaryllidaceae plants: a review. Phytochemistry Reviews 2021; 20: 409–431.
- [12] Nikolova M, Gevrenova, R. Determination of phenolic acids in Amaryllidaceae spesies by high performance liquid chromatography. Pharmaceutical Biology 2005; 43(3): 289-291.
- [13] Berkov S, Bastida J, Tsvetkova R, Viladomat F, Codina C. Alkaloids from Sternbergia colchiciflora. Zeitschrift für Naturforschung 2009; 64c: 311-316.
- [14] Kükcüoglu M, Baser KHC. Headspace Volatiles of Three Turkish Plants. Journal of Essential Oil Research 2010; 22: 389-392.
- [15] Kaya G. Chemical compounds and biological activities of Sternbergia Waldst. & Kit. species. Marmara Pharmaceutical Journal 2014; 15(2): 52-57.
- [16] Varol Ö, Dogru A, Kaya, E. Yilanli Daği (Muğla)'nin florasi. Ekoloji 2004; 13(50): 23-32.
- [17] Kaya E, Varol Ö, Aktaş-Aytepe H. Urban Flora of Muğla (Muğla, Turkey). Flora Mediterranea 2008; 18: 127-148.
- [18] Saraç N, Şen B. Antioxidant, mutagenic, antimutagenic activities, and phenolic compounds of Liquidambar orientalis Mill. var. orientalis. Industrial Crops and Products 2014; 53: 60-64.
- [19] Polat MM, Kaya E, Kivrak I. Comparative chromatographic analysis of phenolic compounds of Liquidambar orientalis plant cultivated under in vitro salt stress. International Journal of Secondary Metabolite 2023; 10(4): 570-582.
- [20] Çelik O, Kaya E. mRNA Transcription Analyses of ROS Genes of Olea europaea L. in vitro Cultures Treated with Different Boron Salts. Journal of Aegean Agricultural Research Institute 2024; 34(1): 24-32.
- [21] Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 1983; 65: 55-63.
- [22] Livak KJ, Schmittge TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 2001; 25(4): 402-408.
- [23] Çiçek S, Ağar H, Galatalı S, Kaya E. Transcriptomic analysis of AREB1 and AREB2 genes playing important roles in drought stress tolerance in tomato under in vitro drought stress. Environmental Analysis & Ecology Studies 2023; 10: 1203-1209.
- [24] Galatali S, Kaya E. Investigation of the Cold Stress Effect on mac_4 (HSP80-Like) Gene at Transcriptional Level for Mentha × piperita L. Modern Concepts & Developments in Agronomy 2022; 10(5): 1057-1059.
- [25] Wei Y, Zhang L, Wang C, Li Z, Luo M, Xie G, Gong JN. Anti‐apoptotic protein BCL‐XL as a therapeutic vulnerability in gastric cancer. Animal Models and Experimental Medicine 2023; 6(3): 245-254.
- [26] Alves da Costa F, Ramos A, Bernardo C, Cardoso Borges F, Costa Miranda A. Epidemiological and clinical characterization of a population-based cohort of cutaneous malignant melanoma patients in the South Region of Portugal. Scientific Reports 2023; 13(1): 5641.
- [27] Rastrelli M, Tropea S, Rossi CR, Alaibac M. Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In vivo 2014; 28(6): 1005-1011.
- [28] Grazziotin TC, Lovatto L, Riccardi F, Pizzol A, dos Santos AP. Melanoma. In Dermatology in Public Health Environments: A Comprehensive Textbook 2017; 341-366. Cham: Springer International Publishing.
- [29] Ferri D, Ubaldi C, Marcozzi G, Fasciani P, Bacchetta L, Pace L. Chemical characterization of Narcissus poeticus from Sirente–Velino (Apennines-Italy): Galantamine accumulation and distribution of allergenic compounds in the flower. Natural Product Communications 2017; 12(1): 15-18.
- [30] Lamoral-Theys D, Andolfi A, Van Goietsenoven G, Cimmino A, Le Calvé B, Wauthoz N, Evidente A. Lycorine, the main phenanthridine Amaryllidaceae alkaloid, exhibits significant antitumor activity in cancer cells that display resistance to proapoptotic stimuli: an investigation of structure− activity relationship and mechanistic insight. Journal of medicinal chemistry 2009; 52(20): 6244-6256.
- [31] Citoglu GS, Yilmaz BS, Bahadir O. Quantitative analysis of lycorine in Sternbergia species growing in Turkey. Chemistry of Natural Compounds 2008; 44: 826-828.
- [32] Masi M, Gunawardana S, van Rensburg MJ, James PC, Mochel JG, Heliso PS, Evidente A. Alkaloids isolated from Haemanthus humilis Jacq., an indigenous South African Amaryllidaceae: Anticancer activity of coccinine and montanine. South African Journal of Botany 2019; 126: 277-281.
DETERMINATION OF THE ANTIPROLIFERATIVE EFFECT OF STERNBERGIA LUTEA (L.) KER GAWL. EX SPRENG. EXTRACTS ON A375 MALIGNANT MELONOMA CELL LINE
Yıl 2025,
Cilt: 14 Sayı: 1, 25 - 33, 29.01.2025
Zemheri Şaman
,
Sevil Yeniocak
,
İrem Demir
,
Ergun Kaya
,
Nurdan Saraç
Öz
Epidemiological evidence confirms that plants are primary sources of drugs used to reduce the incidence of cancer and prevent cancer-related deaths. Sternbergia species are used for therapeutic purposes due to the amaryllidaceae alkaloids, lectins, phenolic acids, pigments, and volatile components they contain. In this study, the anticancer properties of S. lutea extracts were tested on the A375 malignant melonoma cell line. In addition, in the study, the transcriptional expression of BCL-XL and Cas9 genes, which function in cell proliferation and apoptotic pathways, in cells treated with plant extracts were determined by qRT-PCR. According to the cytotoxicity results made by the MTT test, the highest inhibition percentage was determined at the plant's concentration of 500 μg/𝑚L. At this concentration, A375 cells were inhibited by 83.63%, and the IC50 value of the extract was calculated as 194.64 μg/𝑚L. In addition, in qRT-PCR analyses, a statistically significant increase was observed in the mRNA expression levels of Cas9 genes, which are positively correlated with the apoptotic pathway, in the extract and cisplatin-applied groups compared to the control group.
Teşekkür
This study is derived from Zemheri ŞAMAN’s master's thesis. This study was supported by The Scientific and Technological Research Council of Türkiye TUBITAK-2210-A Domestic General Baster's Degree Scholarship Program, and the authors would like to thank the institution.
Kaynakça
- [1] Yuan H, Ma Q, Ye L, Piao G. The Traditional Medicine and Modern Medicine from Natural Products. Molecules (2016); 21(5): 559.
- [2] Thomford NE, Senthebane DA, Rowe A, Munro D, Seele P, Maroyi A, Dzobo K. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery. International Journal of Molecular Sciences 2018; 19(6): 1578.
- [3] Abdul Ghafoor N, Galatali S, Yeniocak S, Kaya E, Sarac N, Ugur A. Investigating anticancer potency of in vitro propagated endemic Thymus cilicicus Boiss. & Bal. extract on human lung, breast, and prostate cancer cell lines. Biologia 2022; 77: 3229-3239.
- [4] Najmi A, Javed SA, Al Bratty M, Alhazmi HA. Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents. Molecules 2022; 27(2): 349.
- [5] Chaachouay N, Zidane L. Plant-Derived Natural Products: A Source for Drug Discovery and Development. Drugs and Drug Candidates 2024; 3(1): 184-207.
- [6] Kaya E, Galatalı S, Güldağ S, Öztürk B, Ceylan M, Çelik O, Aktay İ. Mass production of medicinal plants for obtaining secondary metabolite using liquid mediums via bioreactor systems: SETISTM and RITA®. Turkish Journal of Scientific Reviews 2018; 11(2): 5-10.
- [7] Kivrak S, Göktürk T, Kivrak I, Kaya E, Karababa E. Investigation of phenolic profiles and antioxidant activities of some Salvia species commonly grown in Southwest Anatolia using UPLC-ESI-MS/MS. Food Science and Biotechnology 2019; 39: 423-431.
- [8] Mucha P, Skoczyńska A, Małecka M, Hikisz P, Budzisz E. Overview of the Antioxidant and Anti-Inflammatory Activities of Selected Plant Compounds and Their Metal Ions Complexes. Molecules 2021; 26(16): 4886.
- [9] Yeniocak S, Galatalı S, Demir İ, Uğur A, Saraç N, Kaya E. Investigation of biological activities of in vitro grown Sesamum orientale plant extract on the cell cultures: wound healing and antiproliferation. Advances in Traditional Medicine 2024; 1-14.
- [10] Youssef S, Mahmood A, Vela E. On the genus Sternbergia (Amaryllidaceae) in Iraq. Anales Del Jardín Botánico De Madrid 2017; 74(1): e053.
- [11] Desgagné-Penix I. Biosynthesis of alkaloids in Amaryllidaceae plants: a review. Phytochemistry Reviews 2021; 20: 409–431.
- [12] Nikolova M, Gevrenova, R. Determination of phenolic acids in Amaryllidaceae spesies by high performance liquid chromatography. Pharmaceutical Biology 2005; 43(3): 289-291.
- [13] Berkov S, Bastida J, Tsvetkova R, Viladomat F, Codina C. Alkaloids from Sternbergia colchiciflora. Zeitschrift für Naturforschung 2009; 64c: 311-316.
- [14] Kükcüoglu M, Baser KHC. Headspace Volatiles of Three Turkish Plants. Journal of Essential Oil Research 2010; 22: 389-392.
- [15] Kaya G. Chemical compounds and biological activities of Sternbergia Waldst. & Kit. species. Marmara Pharmaceutical Journal 2014; 15(2): 52-57.
- [16] Varol Ö, Dogru A, Kaya, E. Yilanli Daği (Muğla)'nin florasi. Ekoloji 2004; 13(50): 23-32.
- [17] Kaya E, Varol Ö, Aktaş-Aytepe H. Urban Flora of Muğla (Muğla, Turkey). Flora Mediterranea 2008; 18: 127-148.
- [18] Saraç N, Şen B. Antioxidant, mutagenic, antimutagenic activities, and phenolic compounds of Liquidambar orientalis Mill. var. orientalis. Industrial Crops and Products 2014; 53: 60-64.
- [19] Polat MM, Kaya E, Kivrak I. Comparative chromatographic analysis of phenolic compounds of Liquidambar orientalis plant cultivated under in vitro salt stress. International Journal of Secondary Metabolite 2023; 10(4): 570-582.
- [20] Çelik O, Kaya E. mRNA Transcription Analyses of ROS Genes of Olea europaea L. in vitro Cultures Treated with Different Boron Salts. Journal of Aegean Agricultural Research Institute 2024; 34(1): 24-32.
- [21] Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 1983; 65: 55-63.
- [22] Livak KJ, Schmittge TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 2001; 25(4): 402-408.
- [23] Çiçek S, Ağar H, Galatalı S, Kaya E. Transcriptomic analysis of AREB1 and AREB2 genes playing important roles in drought stress tolerance in tomato under in vitro drought stress. Environmental Analysis & Ecology Studies 2023; 10: 1203-1209.
- [24] Galatali S, Kaya E. Investigation of the Cold Stress Effect on mac_4 (HSP80-Like) Gene at Transcriptional Level for Mentha × piperita L. Modern Concepts & Developments in Agronomy 2022; 10(5): 1057-1059.
- [25] Wei Y, Zhang L, Wang C, Li Z, Luo M, Xie G, Gong JN. Anti‐apoptotic protein BCL‐XL as a therapeutic vulnerability in gastric cancer. Animal Models and Experimental Medicine 2023; 6(3): 245-254.
- [26] Alves da Costa F, Ramos A, Bernardo C, Cardoso Borges F, Costa Miranda A. Epidemiological and clinical characterization of a population-based cohort of cutaneous malignant melanoma patients in the South Region of Portugal. Scientific Reports 2023; 13(1): 5641.
- [27] Rastrelli M, Tropea S, Rossi CR, Alaibac M. Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In vivo 2014; 28(6): 1005-1011.
- [28] Grazziotin TC, Lovatto L, Riccardi F, Pizzol A, dos Santos AP. Melanoma. In Dermatology in Public Health Environments: A Comprehensive Textbook 2017; 341-366. Cham: Springer International Publishing.
- [29] Ferri D, Ubaldi C, Marcozzi G, Fasciani P, Bacchetta L, Pace L. Chemical characterization of Narcissus poeticus from Sirente–Velino (Apennines-Italy): Galantamine accumulation and distribution of allergenic compounds in the flower. Natural Product Communications 2017; 12(1): 15-18.
- [30] Lamoral-Theys D, Andolfi A, Van Goietsenoven G, Cimmino A, Le Calvé B, Wauthoz N, Evidente A. Lycorine, the main phenanthridine Amaryllidaceae alkaloid, exhibits significant antitumor activity in cancer cells that display resistance to proapoptotic stimuli: an investigation of structure− activity relationship and mechanistic insight. Journal of medicinal chemistry 2009; 52(20): 6244-6256.
- [31] Citoglu GS, Yilmaz BS, Bahadir O. Quantitative analysis of lycorine in Sternbergia species growing in Turkey. Chemistry of Natural Compounds 2008; 44: 826-828.
- [32] Masi M, Gunawardana S, van Rensburg MJ, James PC, Mochel JG, Heliso PS, Evidente A. Alkaloids isolated from Haemanthus humilis Jacq., an indigenous South African Amaryllidaceae: Anticancer activity of coccinine and montanine. South African Journal of Botany 2019; 126: 277-281.