Anti-Colorectal Cancer Effects of Medicinal Plants: Euphorbia helioscopia, Ferula elaeochytris, and Sideritis albiflora

Abstract

Phytochemicals, extracts, and mixtures obtained from plants have been offered as an option for cancer treatment and prevention for modern drug discovery in recent years. For this purpose, in this study, anti-colorectal cancer effects of the hexane, acetone, methanol, and water extracts obtained by sequential extraction from Euphorbia helioscopia L., Ferula elaeochytris Korovin, and Sideritis albiflora Hub.-Mor. on DLD-1 cell line were investigated in vitro by using Alamar blue assay. Dose-dependent inhibition was detected in the viability of DLD-1 cell line. In all three plants species, E. helioscopia (IC50: 140.83±0.31 µg/mL), F. elaeochytris (IC50: 67.93±0.12 µg/mL), and S. albiflora (IC50: 85.12±0.10 µg/mL) methanol extracts showed higher anti-colorectal effects on DLD-1 cell line compared to other extracts tested for the same species. In addition, the IC50 value of doxorubicin used as a standard was found as 6.10±0.55 µg/mL. With the results obtained, as the first report highlighting in vitro anti-colorectal cancer effects of the studied plant species on DLD-1 cell line, promising marks were obtained from the analysis of the extracts as anti-cancer sources for plant-derived drug applications.

Keywords

• Plant species
• extracts
• cytotoxic activity
• DLD-1 cell line
• Alamar blue assay

Tıbbi Bitkilerin Anti-Kolorektal Kanser Etkileri: Euphorbia helioscopia, Ferula elaeochytris ve Sideritis albiflora

Abstract

Bitkilerden elde edilen fitokimyasallar, ekstreler ve karışımlar, son yıllarda modern ilaç keşfi için kanser tedavisinde ve önlenmesinde bir seçenek olarak sunulmuştur. Bu amaçla, bu çalışmada sıralı ekstraksiyon kullanılarak Euphorbia helioscopia L., Ferula elaeochytris Korovin ve Sideritis albiflora Hub.-Mor. bitkilerinden elde edilen hekzan, aseton ve metanol ekstrelerinin DLD-1 hücre hattı üzerindeki anti-kolorektal kanser etkileri Alamar mavisi testi kullanılarak in vitro olarak incelendi. DLD-1 hücre hattının canlılığında doza bağlı inhibisyon tespit edildi. Üç bitki türünün hepsinde, E. helioscopia (IC50: 140.83±0.31 µg/mL), F. elaeochytris (IC50: 67.93±0.12 µg/mL) ve S. albiflora (IC50: 85.12±0.10 µg/mL) metanol ekstreleri aynı türler için test edilen diğer ekstrelere kıyasla DLD-1 hücre hattı üzerine daha yüksek anti-kolorektal kanser etkisi gösterdi. İlaveten, standart olarak kullanılan doksorubisinin IC50 değeri 6.10±0.55 µg/mL olarak belirlendi. İncelenen bitki türlerinin DLD-1 hücre hattı üzerindeki in vitro anti-kolorektal kanser etkilerini vurgulayan bu ilk çalışma ile bitki kaynaklı ilaç uygulamaları için anti-kanser kaynakları olarak ekstraktların analizinden umut verici sonuçlar ortaya çıkarıldı.

Keywords

• Bitki türleri
• ekstre
• sitotoksik aktivite
• DLD-1 hücre hattı
• Alamar mavisi testi

References

1. Abutaha, N., Nasr, F. A., Al-zharani, M., Alqahtani, A. S., Noman, O. M., Mubarak, M. S., … Wadaan, M. A. (2019). Effects of hexane root extract of Ferula hermonis Boiss. on human breast and colon cancer cells: an in vitro and in vivo study. BioMed Research International, 2019, 1-12. https://doi.org/10.1155/2019/3079895.
2. Aiello, P., Sharghi, M., Mansourkhani, S. M., Ardekan, A. P., Jouybari, L., Daraei, N., … Kooti, W. (2019). Medicinal plants in the prevention and treatment of colon cancer. Oxidative Medicine and Cellular Longevity, 2019, 1-51. https://doi.org/10.1155/2019/2075614.
3. Aljancic, I.S., Pesic, M., Milosavljevic, S.M., Todorovic, N.M., Jadranin, M., Milosavljevic, G., … Tesevic, V.V. (2011). Isolation and biological evaluation of jatrophane diterpenoids from Euphorbia dendroides. Journal of Natural Products, 74, 1613-1620. https://dx.doi.org/10.1021/np200241c.
4. Altemimi, A., Lakhssassi, N., Baharlouei, A., Watson, D.G., & Lightfoot, D.A. (2017). Phytochemicals: extraction, isolation, and identification of bioactive compounds from plant extracts. Plants, 6, 42. https://doi.org/10.3390/plants6040042.
5. Aras, A., Türkan, F., Yildiko, U., Atalar, M. N., Kılıç, Ö., Alma, M. H., & Bursa, E. (2021). Biochemical constituent, enzyme inhibitory activity, and molecular docking analysis of an endemic plant species. Thymus migricus. Chemical Papers, 75, 1133-1146. https://doi.org/10.1007/s11696-020-01375-z.
6. Askun, T., Tumen, G., Satil, F., & Ates, M. (2009). Characterization of the phenolic composition and antimicrobial activities of Turkish medicinal plants. Pharmaceutical Biology, 47(7), 563-571. https://doi.org/10.1080/13880200902878069.
7. Barbosa, A., Silveira, G. D., de Menezes, I., Neto, J., Bitencurt, J., Estavam, C. D., … dos Santos, M. R. V. (2013). Antidiabetic effect of the Chrysobalanus icaco L. aqueous extract in rats. Journal of Medicinal Food, 16, 538-543. https://doi.org/10.1089/jmf.2012.0084.
8. 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.

9. Baykan, S., Aydogan, F., Ozturk, M. B., Debelec-Butuner, B., Yengin, C., & Ozturk, B. (2020). Ferutinin content and cytotoxic effects of various Ferula L. species on prostate cancer (PC-3) cell line. Journal of Research in Pharmacy, 24(1), 142-149. https://doi.org/10.35333/jrp.2020.120.
10. Chiang, E. P. I., Tsai, S. Y., Kuo, Y. H., Pai, M. H., Chiu, H. L., Rodriguez, R. L., & Tang, F. Y. (2014). Caffeic Acid Derivatives Inhibit the growth of colon cancer: involvement of the PI3-K/Akt and AMPK signaling pathways. Plos One, 9(6), e99631. https://doi.org/10.1371/journal.pone.0099631.
11. Chromanska, A. C., Kulbacka, J., Harasym, J., Dubi, M., Magıera, S., & Saczko, J. (2017). Anticancer activity of oat β-Glucan in combination with electroporation on human cancer cells. Acta Poloniae Pharmaceutica-Drug Research, 74, 616-623.
12. Demir, T., & Akpınar, Ö. (2020). Biological activities of phytochemicals in plants. Turkish Journal of Agriculture-Food Science and Technology, 8(8), 1734-1746. https://doi.org/10.24925/turjaf.v8i8.1734-1746.3484.
13. Deveci, E., Tel-Çayan, G., & Duru, M. E. (2018a). Investigation of chemical composition, antioxidant, anticholinesterase and anti-urease activities of Euphorbia helioscopia. International Journal of Secondary Metabolite, 5, 259-269. https://10.21448/ijsm.433681.
14. Deveci, E., Tel-Çayan, G., & Duru, M. E. (2018b). Phenolic profile, antioxidant, anticholinesterase, and anti-tyrosinase activities of the various extracts of Ferula elaeochytris and Sideritis stricta. International Journal of Food Properties, 21(1), 771-783. https://doi.org/10.1080/10942912.2018.1431660.
15. Deveci, E., Tel-Cayan, G., & Duru, M. E. (2020). In vitro antidiabetic activity of seven medicinal plants naturally growing in Turkey. European Journal of Biology, 79(1), 23-28. https://doi.org/10.26650/EurJBiol.2020.0011.
16. Deveci, E., Tel‐Çayan, G., Duru, M. E., & Öztürk, M. (2019). Phytochemical contents, antioxidant effects, and inhibitory activities of key enzymes associated with Alzheimer's disease, ulcer, and skin disorders of Sideritis albiflora and Sideritis leptoclada. Journal of Food Biochemistry, 43, e13078. https://doi.org/10.1111/jfbc.13078.
17. Deveci, E., Tel-Çayan, G., Karakurt, S., & Duru, M. E. (2021). Cytotoxic activities of methanol extract and compounds of Porodaedalea pini against colorectal cancer. International Journal of Secondary Metabolite, 8, 40-48. https://doi.org/10.21448/ijsm.793715.
18. Ekor, M. (2013). The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology, 4, 177. https://doi.org/10.3389/fphar.2013.00177.
19. El-Hallouty, S., Batawi, A., Shafi, M., Rashwan, E., Elhawary, E., & Abdelaal, N. (2020). Cytotoxicity of five plant extracts against different human cancer cell lines and their molecular mechanism. Asian Journal of Pharmaceutical and Clinical Research, 13, 194-198. https://doi.org/10.22159/ajpcr.2020.v13i10.38698.
20. Hamzeloomoghadam, M., Esmaeil, S., Fotoohi, F., Naghibi, F., Pirani, A., & Hajimehdipoor, H. (2013). In vitro evaluation for cytotoxic activity of three Ferula species. International Journal of Pharmaceutical Sciences and Research, 4(7), 2673-2676.
21. Hassanpour, S. H., & Dehghani, M. (2017). Review of cancer from perspective of molecular. Journal of Cancer Research and Practice, 4, 127e129. https://doi.org/10.1016/j.jcrpr.2017.07.001.
22. Karakurt, S., & Adali, O. (2016). Tannic acid inhibits proliferation, migration, invasion of prostate cancer and modulates drug metabolizing and antioxidant enzymes. Anti-Cancer Agents in Medicinal Chemistry, 16(6), 781-789. https://doi.org/10.2174/1871520616666151111115809.
23. Koçyigit, A., Koyuncu, I., Dikilitas, M., Bahedori, F., Türkkan, B. (2016). Cytotoxic genotoxic and apoptotic effects of naringenin oxime relative to naringenin on normal and cancer cell lines. Asian Pacific Journal of Tropical Biomedicine, 6, 872-880. https://doi.org/10.1016/j.apjtb.2016.08.004.
24. Kogiannou, D. A. A., Kalogeropoulos, N., Kefalas, P., Polissiou, M. G., & Kaliora, A. C. (2013). Herbal infusions; their phenolic profile, antioxidant and anti-inflammatory effects in HT29 and PC3 cells. Food and Chemical Toxicology, 61, 152-159. https://doi.org/10.1016/j.fct.2013.05.027.
25. Lahlou, M. (2013). The success of natural products in drug discovery. Pharmacology & Pharmacy, 4, 17-31. https://doi.org/10.4236/pp.2013.43A003.
26. Lin, J., Dou, J., Xu, J., & Aisa, H.A. (2012). Chemical composition, antimicrobial and antitumor activities of the essential oils and crude extracts of Euphorbia macrorrhiza. Molecules, 17, 5030-5039. https://doi.org/10.3390/molecules17055030.
27. Mesas, C., Martínez, R., Ortíz, R., Galisteo, M., López-Jurado, M., Cabeza, L., … Prados, J. (2021). Antitumor effect of the ethanolic extract from seeds of Euphorbia lathyris in colorectal cancer. Nutrients, 13, 566. https://doi.org/10.3390/nu13020566.
28. Ozkan, G., Kamiloglu, S., Ozdal, T., Boyacioglu, D., & Capanoglu, E. (2016). Potential use of Turkish medicinal plants in the treatment of various diseases. Molecules, 21, 257. https://doi.org/10.3390/molecules21030257.
29. Patra, J.K., Lee, G.D.S., Kang, S.S., & Shin, H.S. (2018). Selected commercial plants: A review of extraction and isolation of bioactive compounds and their pharmacological market value. Trends in Food Science & Technology, 82, 89-109. https://doi.org/10.1016/j.tifs.2018.10.001.
30. Singh, H., Kumar, R., Singh, S., Chaudhary, K., Gautam, A., & Raghava, G. P. S. (2016a). Prediction of anticancer molecules using hybrid model developed on molecules screened against NCI-60 cancer cell lines. BMC Cancer, 16, 77. https://doi.org/10.1186/s12885-016-2082-y.
31. Singh, S., Sharma, B., Kanwar, S. S., & Kumar, A. (2016b). Lead Phytochemicals for anticancer drug development. Frontiers in Plant Science, 7, 1667. https://doi.org/10.3389/fpls.2016.01667.
32. Tekeli, Y., Özkaya, A., Tel, A. Z., Sönmez, G. D., & Akocak, S. (2019). Molecular characterization and determination of some biochemical properties of endemic Serratula olygocephala growing in Adıyaman. Commagene Journal of Biology, 3(1), 32-36. https://doi.org/ 10.31594/commagene.559626.
33. Tomou, E. M., Chatziathanasiadou, M. V., Chatzopoulou, P., Tzakos, A. G., & Skaltsa, H. (2020). NMR-based chemical profiling, isolation and evaluation of the cytotoxic potential of the diterpenoid siderol from cultivated Sideritis euboea Heldr. Molecules, 25, 2382. https://doi.org/10.3390/molecules25102382.
34. Truong, D. H., Nguyen, D. H., Ta, N. T. A., Bui, A.V., Do, T.H., & Nguyen, H.C. (2019). Evaluation of the use of different solvents for phytochemical constituents, antioxidants, and in vitro anti-inflammatory activities of Severinia buxifolia. Journal of Food Quality, 2019, 9 pages. https://doi.org/10.1155/2019/8178294.
35. Vickers, A., & Zollman, C. (1999). Herbal medicine. BMJ, 319 (7216), 1050-1053. https://doi.org/10.1136/bmj.319.7216.1050.
36. Wang, Z. Y., Liu, H. P., Zhang, Y. C., Guo, L. Q., Li, Z. X., & Shi, X. F. (2012). Anticancer potential of Euphorbia helioscopia L extracts against human cancer cells. The Anatomical Record, 295, 223-233. https://doi.org/10.1002/ar.21517.
37. Wu, Y.S., Ngai, S.C., Goh, B.H., Chan, K.G., Lee, L.H., & Chuah, L.H. (2017). Anticancer activities of surfactin and potential application of nanotechnology assisted surfactin delivery. Frontiers in Pharmacology, 8, 761. https://doi.org/10.3389/fphar.2017.00761.
38. Yang, C.S., Wang, H., Chen, J.X., & Zhang, J. (2014). Effects of tea catechins on cancer signaling pathways. Enzymes, 36, 195-221. https://doi.org/10.1016/B978-0-12-802215-3.00010-0.
39. Yang, Y., Chen, X., Luan, F., Wang, M., Wang, Z., Wang, J., & He, X. (2021). Euphorbia helioscopia L.: A phytochemical and pharmacological overview. Phytochemistry, 184, 112649. https://doi.org/10.1016/j.phytochem.2020.112649.
40. Yuan, H., Ma, Q., Ye, L., & Piao, G. (2016). The traditional medicine and modern medicine from natural products. Molecules, 21, 559. https://doi.org/10.3390/molecules21050559.