Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer

Kübra Uzun; Aslıhan Sena Köşker

doi:10.18016/ksutarimdoga.vi.1768714

TR EN

Inula heterolepis Boiss. (Asteraceae) Prostat Kanseri Üzerindeki Sitotoksik, Koloni Oluşturucu ve Anti-migratör Etkilerinin Araştırılması

Öz

Bu çalışma Inula heterolepis'ten elde edilen farklı ekstre ve fraksiyonların sitotoksisitesini, koloni oluşumunu ve anti-migratör etkilerini araştırmayı amaçlamaktadır. Bu çalışmada ekstre ve fraksiyonların LNCaP ve HGF-1 hücrelerine karşı sitotoksik aktiviteleri MTT yöntemi ile araştırılmıştır. Ayrıca LNCaP hücreleri üzerinde 2 boyutlu koloni oluşumu ve in vitro hücre migrasyon deneyleri yapılmıştır. Sonuçlara göre kloroform fraksiyonu en aktif örnek olup, LNCaP hücrelerine karşı 12.91 ± 0,61 μg mL-1'lik bir IC50 değeriyle umut verici sitotoksik aktiviteye sahiptir. 10 μg mL-1'de değerlendirilen tüm ekstre ve fraksiyonlar 2 boyutlu koloni oluşumu deneyinde koloni oluşumunu azaltmıştır (p<.0001). Kloroform fraksiyonu ayrıca 24 ve 36. saatlerde hücre migrasyonunu da engellemiştir (p<.027). Sonuç olarak, n-butanol fraksiyonu hariç, test edilen tüm numuneler, LNCaP hücreleri üzerinde konsantrasyona bağlı olarak sitotoksik aktivite göstermiştir. Bu, Inula heterolepis'in LNCaP ve HGF-1 hücrelerine karşı ilk sitotoksik aktivite çalışmasıdır. Bu çalışma, Inula heterolepis ekstrelerinin prostat kanserine karşı daha ileri çalışmalar için mükemmel bir potansiyele sahip olduğunu göstermektedir.

Anahtar Kelimeler

Proje Numarası

TLO-224-13814

Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer

Öz

This study aimed to investigate the cytotoxicity, colony formation, and anti-migratory effects of different extracts and fractions derived from Inula heterolepis. In this study, the cytotoxic activities of the extracts against LNCaP and HGF-1 cells were investigated by the MTT method. It was also performed as a 2-dimensional colony formation and in vitro cell migration assay on LNCaP cells. According to the results, the chloroform fraction is the most active sample, and it has promising cytotoxic activity with an IC50 value of 12.91±0.61 μg mL-1 against the LNCaP cells. All extracts and fractions evaluated at 10 μg mL-1 decreased colony formation in the 2-dimensional colony formation experiment (p<.0001). The chloroform fraction also inhibited cell migration at 24 and 36 hours (p<.027). In conclusion, all the tested extracts and fractions, except for the n-butanol fraction, showed cytotoxic activity on LNCaP cells in a concentration-dependent manner. It is the first cytotoxic activity study of Inula heterolepis against LNCaP and HGF-1 cells. This observation suggests that Inula heterolepis extracts have excellent potential for further studies against prostate cancer.

Anahtar Kelimeler

Destekleyen Kurum

Erciyes University Scientific Research Projects

Proje Numarası

TLO-224-13814

Etik Beyan

A decision from the ethics committee is not necessary for the work. We, the authors of this article, affirm that the data, information, and documents herein were acquired in adherence to academic and ethical standards, and that all information, documents, evaluations, and results are presented in compliance with scientific ethics and moral principles.

Teşekkür

The financial support from Erciyes University Scientific Research Projects (under project code TLO-2024-13814) is gratefully acknowledged. This study covers the undergraduate thesis at Erciyes University Faculty of Pharmacy. Also many thanks to Dr. Yalçın ERZURUMLU and Dr. İrem ÖNAL, who kindly gifted the cell lines.

Kaynakça

Abu-Dahab, R., & Afifi, F. (2007). Antiproliferative activity of selected medicinal plants of Jordan against a breast adenocarcinoma cell line (MCF7). Scientia pharmaceutica, 75(3), 121-146. https://doi.org/ 10.3797/scipharm.2007.75.121
Ayaz, M., Nawaz, A., Ahmad, S., Mosa, O. F., Eisa Hamdoon, A. A., Khalifa, M. A., ... & Ananda Murthy, H. C. (2022). Underlying anticancer mechanisms and synergistic combinations of phytochemicals with cancer chemotherapeutics: potential benefits and risks. Journal of Food Quality, 2022(1), 1189034.
Aygün, A., Kılınç, F., Özmen, A. S., Bayram, M. E., Kiper, A. N., Uzun, K., Doğan, Ş. D., Gündüz, M. G., Cumaoğlu, A., & Gürbüz, P. (2025). Cytotoxicity-guided isolation of acacetin derivatives from Cirsium rhizocephalum CA Mey.(Asteraceae) and their in silico investigation for androgen receptor inhibition against prostate cancer. Chemical Papers, 1-10. (∈press) https://doi.org/10.1007/s11696-025-04162-w
Bach, C., Pisipati, S., Daneshwar, D., Wright, M., Rowe, E., Gillatt, D., Persad, R., & Koupparis, A. (2014). The status of surgery in the management of high-risk prostate cancer. Nature Reviews Urology, 11(6), 342-351. https://doi.org/10.1038/nrurol.2014.100
Bar-Shalom, R., Bergman, M., Grossman, S., Azzam, N., Sharvit, L., & Fares, F. (2019). Inula viscosa extract inhibits growth of colorectal cancer cells in vitro and in vivo through induction of apoptosis. Frontiers in oncology, 9, 227. https://doi.org/10.3389/fonc.2019.00227
Berenguer, C. V., Pereira, F., Câmara, J. S., & Pereira, J. A. (2023). Underlying features of prostate cancer—statistics, risk factors, and emerging methods for its diagnosis. Current Oncology, 30(2), 2300-2321. https://doi.org/10.3390/curroncol30020178
Bohlmann, F., Ates, N., & Grenz, M. (1982). New germacranolides from Inula heterolepis. Phytochemistry, 21(5), 1166-1168. https://doi.org/10.1016/S0031-9422(00)82444-9
Bunz, F., & Bunz, F. (2016). Cancer genetics in the clinic. Principles of cancer genetics, 305-336. https://doi.org/10.1007/978-94-017-7484-0_8

Chambers, A. F., Groom, A. C., & MacDonald, I. C. (2002). Dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer, 2(8), 563-572. https://doi.org/10.1038/nrc865
Colak, D. K., Egeli, U., Eryilmaz, I. E., Aybastier, O., Malyer, H., Cecener, G., & Tunca, B. (2022). The Anticancer Effect of Inula viscosa Methanol Extract by miRNAs’ Re-regulation: An in vitro Study on Human Malignant Melanoma Cells. Nutrition and cancer, 74(1), 211-224. https://doi.org/10.1080/01635581.2020.1869791
Das, A., Shakya, A., Ghosh, S. K., Singh, U. P., & Bhat, H. R. (2020). A review of phytochemical and pharmacological studies of Inula species. Current Bioactive Compounds, 16(5), 557-567. https://doi.org/10.2174/1573407215666190207093538
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
Friedl, P., & Wolf, K. (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nature Reviews Cancer, 3(5), 362-374. https://doi.org/10.1038/nrc1075
Güner, A., Akyıldırım, B., Alkayış, M., Çıngay, B., Kanoğlu, S., Özkan, A., Öztekin, M., & Tuğ, G. (2012). Türkçe bitki adları. Şu eserde: Güner, A., aslan, S. Ekim, T. Vural, M. & Babaç, MT (edlr.). Türkiye Bitkileri Listesi (Damarlı Bitkiler). Nezahat Gökyiğit Botanik Bahçesi Yayınları Flora Dizisi, 1.
Huang, M., Lu, J.-J., & Ding, J. (2021). Natural products in cancer therapy: Past, present and future. Natural products and bioprospecting, 11(1), 5-13. https://doi.org/10.1007/s13659-020-00293-7
Indrayanto, G., Putra, G. S., & Suhud, F. (2021). Validation of in-vitro bioassay methods: Application in herbal drug research. Profiles of drug substances, excipients and related methodology, 46, 273-307. https://doi.org/10.1016/bs.podrm.2020.07.005
Kaileh, M., Berghe, W. V., Boone, E., Essawi, T., & Haegeman, G. (2007). Screening of indigenous Palestinian medicinal plants for potential anti-inflammatory and cytotoxic activity. Journal of ethnopharmacology, 113(3), 510-516. https://doi.org/10.1016/j.jep.2007.07.008
Karaboğa-Arslan, A.K., Güngörenler, E., Paşayeva, L., Bozkurt, M.N., & Tugay, O. (2025). Evaluation of Cytotoxicity of Centaurea lycaonica Boiss. & Heldr. Plant on Human Cervical Cancer Cell Line with MTT Test and xCELLigence System. KSU J. Agric Nat 28 (1), 47-52. https://doi.org/10.18016/ksutarimdoga.vi.1496499
Karacaoğlu, M., Gökbulut, A., Özhan, O., & Şarer, E. (2013). In vitro antioxidant activity, total phenolic content and phenolic composition of Inula heterolepis. Planta medica, 79(13), PJ24. https://doi.org/10.1055/s-0033-1352228.
Kaynak, B., Aydogdu, G., Koloren, Z., & Koloren, O. (2025). Investigation of the Anticancer Effects on Human Cervical Cancer (HeLa) Cell Line and the DNA Protective Activities of Traditional Plants from Ordu Province (Brassica oleracea var. viridis, Smilax excelsa, Conium maculatum). KSU J. Agric Nat 28(4), 945-954. (∈press) https://doi.org/10.18016/ksutarimdoga.vi.1651205.
Khazir, J., Mir, B. A., Pilcher, L., & Riley, D. L. (2014). Role of plants in anticancer drug discovery. Phytochemistry Letters, 7, 173-181. https://doi.org/10.1016/j.phytol.2013.11.010
Koc, K., Ozdemir, O., Ozdemir, A., Dogru, U., & Turkez, H. (2018). Antioxidant and anticancer activities of extract of Inula helenium (L.) in human U-87 MG glioblastoma cell line. Journal of cancer research and therapeutics, 14(3), 658-661. https://doi.org/ 10.4103/0973-1482.187289
Li, X., Yang, X., Liu, Y., Gong, N., Yao, W., Chen, P., Qin, J., Jin, H., Li, J., & Chu, R. (2013). Japonicone A suppresses growth of Burkitt lymphoma cells through its effect on NF-κB. Clinical Cancer Research, 19(11), 2917-2928. https://doi.org/10.1158/1078-0432.CCR-12-3258
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.
Lin, D. L., Tarnowski, C. P., Zhang, J., Dai, J., Rohn, E., Patel, A. H., Morris, M. D., & Keller, E. T. (2001). Bone metastatic LNCaP‐derivative C4‐2B prostate cancer cell line mineralizes in vitro. The Prostate, 47(3), 212-221. https://doi.org/10.1002/pros.1065
Merghoub, N., Benbacer, L., Amzazi, S., Morjani, H., & El-Mzibri, M. (2009). Cytotoxic effect of some Moroccan medicinal plant extracts on human cervical cell lines. Journal of Medicinal Plants Research, 3(12), 1045-1050. https://doi.org/ /10.5555/20103012489
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J.Immunol. Methods, 65. https://doi.org/10.1016/0022-1759(83)90303-4
Munshi, A., Hobbs, M., & Meyn, R. E. (2005). Clonogenic cell survival assay. In Chemosensitivity: Volume 1 In Vitro Assays (pp. 21-28). Springer. https://doi.org/10.1385/1-59259-869-2:021
Nader, R., El Amm, J., & Aragon-Ching, J. B. (2018). Role of chemotherapy in prostate cancer. Asian journal of andrology, 20(3), 221-229.
Pal, H. C., Sehar, I., Bhushan, S., Gupta, B. D., & Saxena, A. K. (2010). Activation of caspases and poly (ADP-ribose) polymerase cleavage to induce apoptosis in leukemia HL-60 cells by Inula racemosa. Toxicology in vitro, 24(6), 1599-1609. https://doi.org/10.1016/j.tiv.2010.06.007
Peña-Morán, O. A., Villarreal, M. L., Álvarez-Berber, L., Meneses-Acosta, A., & Rodríguez-López, V. (2016). Cytotoxicity, post-treatment recovery, and selectivity analysis of naturally occurring podophyllotoxins from Bursera fagaroides var. fagaroides on breast cancer cell lines. Molecules, 21(8), 1013. https://doi.org/10.3390/molecules21081013
Plumb, J. A. (2004). Cell sensitivity assays: clonogenic assay. In Cancer cell culture: methods and protocols (pp. 159-164). Totowa, NJ: Humana Press.
POWO. (2026). https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:77178425-1
Seca, A. M., Grigore, A., Pinto, D. C., & Silva, A. M. (2014). The genus Inula and their metabolites: From ethnopharmacological to medicinal uses. Journal of ethnopharmacology, 154(2), 286-310. https://doi.org/10.1016/j.jep.2014.04.010
Sekhoacha, M., Riet, K., Motloung, P., Gumenku, L., Adegoke, A., & Mashele, S. (2022). Prostate cancer review: genetics, diagnosis, treatment options, and alternative approaches. Molecules, 27(17), 5730. https://doi.org/10.3390/molecules27175730
Sevindik, E., Aydin, S., Paksoy, M. Y., & Sokmen, B. B. (2020). Anti-urease, total phenolic content and antioxidant activities of some Inula L. (Asteraceae) taxa in Turkey. Genetika, 52(3), 825-834. https://doi.org/10.2298/GENSR2003825S
Virdis, P., Migheli, R., Galleri, G., Fancello, S., Cadoni, M. P. L., Pintore, G., Petretto, G. L., Marchesi, I., Fiorentino, F. P., & di Francesco, A. (2020). Antiproliferative and proapoptotic effects of Inula viscosa extract on Burkitt lymphoma cell line. Tumor Biology, 42(2), 1010428319901061. https://doi.org/10.1177/1010428319901061
Wang, G.-W., Qin, J.-J., Cheng, X.-R., Shen, Y.-H., Shan, L., Jin, H.-Z., & Zhang, W.-D. (2014). Inula sesquiterpenoids: structural diversity, cytotoxicity and anti-tumor activity. Expert Opinion on Investigational Drugs, 23(3), 317-345. https://doi.org/10.1517/13543784.2014.868882
Weerapreeyakul, N., Nonpunya, A., Barusrux, S., Thitimetharoch, T., & Sripanidkulchai, B. (2012). Evaluation of the anticancer potential of six herbs against a hepatoma cell line. Chinese medicine, 7(1), 1-7. https://doi.org/10.1186/1749-8546-7-15
Yamaguchi, H., Wyckoff, J., & Condeelis, J. (2005). Cell migration in tumors. Current opinion in cell biology, 17(5), 559-564. https://doi.org/10.1016/j.ceb.2005.08.002
Yan, Y., Zhang, Q., Zhang, B., Yang, B., & Lin, N. (2020). Active ingredients of Inula helenium L. exhibits similar anti-cancer effects as isoalantolactone in pancreatic cancer cells. Natural Product Research, 34(17), 2539-2544. https://doi.org/10.1080/14786419.2018.1543676
Yang, L., Wang, X., Hou, A., Zhang, J., Wang, S., Man, W., Yu, H., Zheng, S., Wang, Q., & Jiang, H. (2021). A review of the botany, traditional uses, phytochemistry, and pharmacology of the Flos Inulae. Journal of ethnopharmacology, 276, 114125. https://doi.org/10.1016/j.jep.2021.114125
Zhang, B., Zeng, J., Yan, Y., Yang, B., Huang, M., Wang, L., Zhang, Q., & Lin, N. (2018). Ethyl acetate extract from Inula helenium L. inhibits the proliferation of pancreatic cancer cells by regulating the STAT3/AKT pathway. Molecular Medicine Reports, 17(4), 5440-5448. https://doi.org/10.3892/mmr.2018.8534
Zhao, Y. M., Zhang, M. L., Shi, Q. W., & Kiyota, H. (2006). Chemical constituents of plants from the genus Inula. Chemistry and Biodiversity, 3(4), 371-384. https://doi.org/10.1002/cbdv.200690041

Ayrıntılar

Birincil Dil

İngilizce

Konular

Eczacılık ve İlaç Bilimleri (Diğer)

Bölüm

Araştırma Makalesi

Yazarlar

Kübra Uzun ^*
0000-0003-0381-5152
Türkiye

Aslıhan Sena Köşker
0009-0002-8540-6802
Türkiye

Erken Görünüm Tarihi

7 Kasım 2026

Yayımlanma Tarihi

-

Gönderilme Tarihi

19 Ağustos 2025

Kabul Tarihi

9 Temmuz 2026

Yayımlandığı Sayı

Yıl 2026 Sayı: Advanced Online Publication

DOI

https://doi.org/10.18016/ksutarimdoga.vi.1768714

IZ

https://izlik.org/JA39LB72ZJ

Kaynak Göster

RIS / Bibtex

APA

Uzun, K., & Köşker, A. S. (2026). Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi, Advanced Online Publication. https://doi.org/10.18016/ksutarimdoga.vi.1768714

AMA

1.Uzun K, Köşker AS. Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi. 2026;(Advanced Online Publication). doi:10.18016/ksutarimdoga.vi.1768714

Chicago

Uzun, Kübra, ve Aslıhan Sena Köşker. 2026. “Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer”. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi, sy Advanced Online Publication. https://doi.org/10.18016/ksutarimdoga.vi.1768714.

EndNote

Uzun K, Köşker AS (07 Kasım 2026) Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi Advanced Online Publication

IEEE

[1]K. Uzun ve A. S. Köşker, “Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer”, Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi, sy Advanced Online Publication, Kas. 2026, doi: 10.18016/ksutarimdoga.vi.1768714.

ISNAD

Uzun, Kübra - Köşker, Aslıhan Sena. “Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer”. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi. Advanced Online Publication (07 Kasım 2026). https://doi.org/10.18016/ksutarimdoga.vi.1768714.

JAMA

1.Uzun K, Köşker AS. Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi. 2026. doi:10.18016/ksutarimdoga.vi.1768714.

MLA

Uzun, Kübra, ve Aslıhan Sena Köşker. “Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer”. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi, sy Advanced Online Publication, Kasım 2026, doi:10.18016/ksutarimdoga.vi.1768714.

Vancouver

1.Kübra Uzun, Aslıhan Sena Köşker. Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi. 07 Kasım 2026;(Advanced Online Publication). doi:10.18016/ksutarimdoga.vi.1768714

Inula heterolepis Boiss. (Asteraceae) Prostat Kanseri Üzerindeki Sitotoksik, Koloni Oluşturucu ve Anti-migratör Etkilerinin Araştırılması

Öz

Anahtar Kelimeler

Proje Numarası

Investigation of Cytotoxic, Colony-forming, and Anti-migratory Effects of Inula heterolepis Boiss. (Asteraceae) on Prostate Cancer

Öz

Anahtar Kelimeler

Destekleyen Kurum

Proje Numarası

Etik Beyan

Teşekkür

Kaynakça

Ayrıntılar

Birincil Dil

Konular

Bölüm

Yazarlar

Erken Görünüm Tarihi

Yayımlanma Tarihi

Gönderilme Tarihi

Kabul Tarihi

Yayımlandığı Sayı

DOI

IZ

Kaynak Göster

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