Year 2025,
Volume: 4 Issue: 2, 56 - 63, 13.12.2025
Özge Çağlar Yıldırım
,
Sena Öner
,
Cihat Aksakal
,
Ceren Karagöz
,
Cemal Metehan Akkuş
,
Hasan Türkez
References
-
1. D.M. M, G.K. F, A.S. F. The challenge of emerging and re-emerging infectious diseases. Nature. 2004.
2. Xu Y, Yuan FE, Chen QX, Liu BH. Molecular mechanisms involved in angiogenesis and potential target of antiangiogenesis in human glioblastomas. Glioma. 2018.
-
3. Biserova K, Jakovlevs A, Uljanovs R, Strumfa I. Cancer stem cells: Significance in origin, pathogenesis and treatment of glioblastoma. Cells. 2021.
-
4. Ekbatan SS, Li XQ, Ghorbani M, Azadi B, Kubow S. Chlorogenic acid and its microbial metabolites exert anti-proliferative effects, S-phase cell-cycle arrest and apoptosis in human colon cancer Caco-2 cells. Int J Mol Sci. 2018;19(3):723. doi:10.3390/ijms19030723.
-
5. Stepp JR. Medicinal plants in folk traditions: an ethnobotany of Britain & Ireland. Econ Bot. 2005;59(4):404–405.
-
6. Akerele O. Nature’s medicinal bounty: don’t throw it away. World Health Forum. 1993;14(4):390–395.
-
7. Hemalswarya S, Doble M. Potential synergism of natural products in the treatment of cancer. Phytother Res. 2006;20(4):239–249. doi:10.1002/ptr.1841
-
8. Moustafa ARA. Distribution behaviour and seed germination of Alkanna orientalis growing in Saint Catherine Protectorate. Pak J Biol Sci. 2002;5(4):427–433.
-
9. Demir A. Economic and ecological importance of Alkanna orientalis var. orientalis (L.) Boiss. Eurasian J For Sci. 2022;10(1):45–52. doi:10.31195/ejejfs.1031607
-
10. Khan UA, Rahman H, Qasim M, Hussain A, Azizllah A, Murad W, et al. Alkanna tinctoria leaves extracts: a prospective remedy against multidrug resistant human pathogenic bacteria. BMC Complement Altern Med. 2015;15:127. doi:10.1186/s12906-015-0646-z
-
11. Sevimli-Gur C, Akgun IH, Deliloglu-Gurhan I, Korkmaz KS, Bedir E. Cytotoxic naphthoquinones from Alkanna cappadocica. J Nat Prod. 2010;73(6):982–986. doi:10.1021/np900778j
-
12. Alsaraf KM, Mohammad MH, Al-Shammari AM, Abbas IS. Selective cytotoxic effect of Plantago lanceolata L. against breast cancer cells. J Egypt Natl Canc Inst. 2019;31(1):6. doi:10.1186/s43046-019-0010-3
-
13. Arslan ME, Tatar A, Yıldırım ÖÇ, Şahin İO, Ozdemir O, Sonmez E, et al. In vitro transcriptome analysis of cobalt boride nanoparticles on human pulmonary alveolar cells. Materials (Basel). 2022;15(23):8686. doi:10.3390/ma15238683
-
14. Küçükdoğru R, Türkez H, Arslan ME, Tozlu ÖÖ, Sönmez E, Mardinoğlu A, et al. Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson’s disease model against MPP+ induced apoptosis. Metab Brain Dis. 2020;35(6):947–957. doi:10.1007/s11011-020-00559-6
-
15. Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2(2):329–333. doi:10.1038/nprot.2007.30
-
16. Hamurci Y, Ihlamur M, Abamor EŞ. Mide kanserine karşı geliştirilen aşı formülasyonunun immünostimülan ve sitotoksik etkilerinin incelenmesi. Balıkesir Univ Fen Bilim Enstitüsü Derg. 2024;26(1):101–110. doi:10.25092/baunfbed.1179656
-
17. Rani V, Chary BC, Muddasani GS, Deshpande S, Venkatesan J, Dalavi PA, et al. Cytotoxic and apoptotic efficacy of Alkanna tinctoria on glioma cells. Nat Prod Res. 2023;37(1):45–53. doi:10.1080/14786419.2022.2155644
-
18. Haghbeen K, Pourmolaei S, Mareftjo MJ, Mousavi A, Akbari Noghabi K, Shirazi FH, et al. Detailed investigations on the solid cell culture and antimicrobial activities of the Iranian Arnebia euchroma. J Biomed Biotechnol. 2011;2011:165852. doi:10.1155/2011/165852
-
19. Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005;100(1–2):72–79. doi:10.1016/j.jep.2005.05.011
-
20. Kosger HH, Ozturk M, Sokmen A, Bulut E, Ay S. Wound healing effects of Arnebia densiflora root extracts on rat palatal mucosa. Eur J Dent. 2009;3(2):114–118.
-
21. Bame JR, Graf TN, Junio HA, Bussey RO, Jarmusch SA, El-Elimat T, et al. Sarothrin from Alkanna orientalis is an antimicrobial agent and efflux pump inhibitor. Planta Med. 2013;79(7):515–522. doi:10.1055/s-0032-1328259
-
22. Dias AMA, Braga MEM, Seabra IJ, Ferreira P, Gil MH, de Sousa HC. Development of natural-based wound dressings impregnated with bioactive compounds and using supercritical carbon dioxide. Int J Pharm. 2011;408(1–2):9–19. doi:10.1016/j.ijpharm.2011.01.063
-
23. Gara RK, Srivastava VK, Duggal S, Bagga JK, Bhatt MLB, Sanyal S, et al. Shikonin selectively induces apoptosis in human prostate cancer cells through the endoplasmic reticulum stress and mitochondrial apoptotic pathway. J Biomed Sci. 2015;22:26. doi:10.1186/s12929-015-0127-1
-
24. Huu Tung N, Du GJ, Wang CZ, Yuan CS, Shoyama Y. Naphthoquinone components from Alkanna tinctoria (L.) Tausch show significant antiproliferative effects on human colorectal cancer cells. Phytother Res. 2013;27(3):497–502. doi:10.1002/ptr.4680
-
25. Lan W, Wan S, Gu W, Wang H, Zhou S. Mechanisms behind the inhibition of lung adenocarcinoma cell by Shikonin. Cell Biochem Biophys. 2014;69(3):489–494. doi:10.1007/s12013-014-0083-5
Cytotoxic, genotoxic and anti-metastatic activity of Alkanna orientalis (L.) extract on glioblastoma multiforme brain cancer
Year 2025,
Volume: 4 Issue: 2, 56 - 63, 13.12.2025
Özge Çağlar Yıldırım
,
Sena Öner
,
Cihat Aksakal
,
Ceren Karagöz
,
Cemal Metehan Akkuş
,
Hasan Türkez
Abstract
This study aimed to evaluate, for the first time, the anti-proliferative and anti-metastatic effects of the aqueous extract of Alkanna orientalis (L.) on U87-MG glioblastoma cells. The cytotoxicity of this extract on normal human dermal fibroblasts and its anti-cancer activity on glioblastoma cells were assessed by using MTT assay. The potential genotoxic effects of the Alkanna orientalis (L.) extract on cell nuclei were further examined by Hoechst 33258 fluorescence staining and analyzed microscopically. In addition, the inhibitory effect of the extract at a selected dose on the metastatic capacity of glioblastoma cells was investigated using in vitro scratch assay. The plant extract demonstrated no significant cytotoxicity in HDF cells at any of the tested concentrations, whereas even the lowest tested dose exhibited notable anti-proliferative activity against U87-MG glioblastoma cells. Hoechst 33258 staining revealed no evidence of genotoxic nuclear alterations in HDF cells treated with 400 µg/mL extract compared to untreated controls. Moreover, the in vitro scratch assay revealed a pronounced inhibition of U87-MG cell migration 24 hours after treatment with this plant extract, indicating a potential anti-metastatic effect. These findings suggest that the aqueous extract of Alkanna orientalis (L.) may represent a promising alternative therapeutic candidate for the treatment of glioblastoma.
References
-
1. D.M. M, G.K. F, A.S. F. The challenge of emerging and re-emerging infectious diseases. Nature. 2004.
2. Xu Y, Yuan FE, Chen QX, Liu BH. Molecular mechanisms involved in angiogenesis and potential target of antiangiogenesis in human glioblastomas. Glioma. 2018.
-
3. Biserova K, Jakovlevs A, Uljanovs R, Strumfa I. Cancer stem cells: Significance in origin, pathogenesis and treatment of glioblastoma. Cells. 2021.
-
4. Ekbatan SS, Li XQ, Ghorbani M, Azadi B, Kubow S. Chlorogenic acid and its microbial metabolites exert anti-proliferative effects, S-phase cell-cycle arrest and apoptosis in human colon cancer Caco-2 cells. Int J Mol Sci. 2018;19(3):723. doi:10.3390/ijms19030723.
-
5. Stepp JR. Medicinal plants in folk traditions: an ethnobotany of Britain & Ireland. Econ Bot. 2005;59(4):404–405.
-
6. Akerele O. Nature’s medicinal bounty: don’t throw it away. World Health Forum. 1993;14(4):390–395.
-
7. Hemalswarya S, Doble M. Potential synergism of natural products in the treatment of cancer. Phytother Res. 2006;20(4):239–249. doi:10.1002/ptr.1841
-
8. Moustafa ARA. Distribution behaviour and seed germination of Alkanna orientalis growing in Saint Catherine Protectorate. Pak J Biol Sci. 2002;5(4):427–433.
-
9. Demir A. Economic and ecological importance of Alkanna orientalis var. orientalis (L.) Boiss. Eurasian J For Sci. 2022;10(1):45–52. doi:10.31195/ejejfs.1031607
-
10. Khan UA, Rahman H, Qasim M, Hussain A, Azizllah A, Murad W, et al. Alkanna tinctoria leaves extracts: a prospective remedy against multidrug resistant human pathogenic bacteria. BMC Complement Altern Med. 2015;15:127. doi:10.1186/s12906-015-0646-z
-
11. Sevimli-Gur C, Akgun IH, Deliloglu-Gurhan I, Korkmaz KS, Bedir E. Cytotoxic naphthoquinones from Alkanna cappadocica. J Nat Prod. 2010;73(6):982–986. doi:10.1021/np900778j
-
12. Alsaraf KM, Mohammad MH, Al-Shammari AM, Abbas IS. Selective cytotoxic effect of Plantago lanceolata L. against breast cancer cells. J Egypt Natl Canc Inst. 2019;31(1):6. doi:10.1186/s43046-019-0010-3
-
13. Arslan ME, Tatar A, Yıldırım ÖÇ, Şahin İO, Ozdemir O, Sonmez E, et al. In vitro transcriptome analysis of cobalt boride nanoparticles on human pulmonary alveolar cells. Materials (Basel). 2022;15(23):8686. doi:10.3390/ma15238683
-
14. Küçükdoğru R, Türkez H, Arslan ME, Tozlu ÖÖ, Sönmez E, Mardinoğlu A, et al. Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson’s disease model against MPP+ induced apoptosis. Metab Brain Dis. 2020;35(6):947–957. doi:10.1007/s11011-020-00559-6
-
15. Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2(2):329–333. doi:10.1038/nprot.2007.30
-
16. Hamurci Y, Ihlamur M, Abamor EŞ. Mide kanserine karşı geliştirilen aşı formülasyonunun immünostimülan ve sitotoksik etkilerinin incelenmesi. Balıkesir Univ Fen Bilim Enstitüsü Derg. 2024;26(1):101–110. doi:10.25092/baunfbed.1179656
-
17. Rani V, Chary BC, Muddasani GS, Deshpande S, Venkatesan J, Dalavi PA, et al. Cytotoxic and apoptotic efficacy of Alkanna tinctoria on glioma cells. Nat Prod Res. 2023;37(1):45–53. doi:10.1080/14786419.2022.2155644
-
18. Haghbeen K, Pourmolaei S, Mareftjo MJ, Mousavi A, Akbari Noghabi K, Shirazi FH, et al. Detailed investigations on the solid cell culture and antimicrobial activities of the Iranian Arnebia euchroma. J Biomed Biotechnol. 2011;2011:165852. doi:10.1155/2011/165852
-
19. Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005;100(1–2):72–79. doi:10.1016/j.jep.2005.05.011
-
20. Kosger HH, Ozturk M, Sokmen A, Bulut E, Ay S. Wound healing effects of Arnebia densiflora root extracts on rat palatal mucosa. Eur J Dent. 2009;3(2):114–118.
-
21. Bame JR, Graf TN, Junio HA, Bussey RO, Jarmusch SA, El-Elimat T, et al. Sarothrin from Alkanna orientalis is an antimicrobial agent and efflux pump inhibitor. Planta Med. 2013;79(7):515–522. doi:10.1055/s-0032-1328259
-
22. Dias AMA, Braga MEM, Seabra IJ, Ferreira P, Gil MH, de Sousa HC. Development of natural-based wound dressings impregnated with bioactive compounds and using supercritical carbon dioxide. Int J Pharm. 2011;408(1–2):9–19. doi:10.1016/j.ijpharm.2011.01.063
-
23. Gara RK, Srivastava VK, Duggal S, Bagga JK, Bhatt MLB, Sanyal S, et al. Shikonin selectively induces apoptosis in human prostate cancer cells through the endoplasmic reticulum stress and mitochondrial apoptotic pathway. J Biomed Sci. 2015;22:26. doi:10.1186/s12929-015-0127-1
-
24. Huu Tung N, Du GJ, Wang CZ, Yuan CS, Shoyama Y. Naphthoquinone components from Alkanna tinctoria (L.) Tausch show significant antiproliferative effects on human colorectal cancer cells. Phytother Res. 2013;27(3):497–502. doi:10.1002/ptr.4680
-
25. Lan W, Wan S, Gu W, Wang H, Zhou S. Mechanisms behind the inhibition of lung adenocarcinoma cell by Shikonin. Cell Biochem Biophys. 2014;69(3):489–494. doi:10.1007/s12013-014-0083-5