Assessment of Cytotoxic Effect of Porodaedalea pini Mushroom on Prostate Cancer

Öz

Phellinus species are in the classification of valuable mushrooms among medicinal mushrooms and have been the source of traditional medicine for centuries. In this study, the hexane (PPH), methanol (PPM) and water (PPW) extracts, fractions and isolated compounds from Porodaedalea pini (Çamkavı mantarı) were screened for their cytotoxic effects on PC3 (prostate cancer) and 3T3 (murine fibroblast) cell lines by MTT assay. PPH was found to have moderate cytotoxicity on PC3 cell with the IC50 values of 33.84±0.01 µg/mL. The fatty acid profile of PPH was identified by GC-FID (gas chromatography-flame ionization dedector) and GC-MS (gas chromatography-mass spectrometry) and the main fatty acids were recorded as palmitic (41.40±0.03%), linoleic (21.53±0.01%), oleic (12.06±0.01%), and stearic (8.20±0.01%) acids. PPM and PPW were fractioned by using liquid-liquid extractions. Among all fractions, the 2-butanol fraction of the methanol extract (PPM-B) indicated the best cytotoxicity on PC3 and 3T3 cell lines. Also, among the isolated compounds (dioctyl phthalate (1), ergosterol peroxide (2) and pinoresinol (3)) from PPM, ergosterol peroxide (2) was found as moderate cytotoxic on PC3 with the IC50 value of 95.47±1.01 µg/mL. This study, in which the effect of P. pini on PC3 cell was examined for the first time, proved its medicinal importance by revealing the cytotoxic properties of the species.

Anahtar Kelimeler

• Porodaedalea pini
• Prostate cancer
• Extract
• Fatty acid
• Isolation

Porodaedalea pini Mantarının Prostat Kanseri Üzerindeki Sitotoksik Etkisinin Değerlendirilmesi

Öz

Phellinus türleri şifalı mantarlar arasındaki değerli mantarlar sınıfında yer almaktadır ve yüzyıllardır geleneksel tıbbın kaynağı olmuştur. Bu çalışmada, Porodaedalea pini (Çamkavı mantarı)'den elde edilen hekzan (PPH), metanol (PPM) ve su (PPW) ekstrelerinin, fraksiyonlarının ve izole edilmiş bileşiklerin PC3 (prostat kanseri) ve 3T3 (fare fibroblast) hücre hatları üzerindeki sitotoksik etkileri MTT testi kullanılarak taranmıştır. PPH’ın 33.84±0.01 µg/mL olan IC50 değeri ile PC3 üzerinde orta derecede sitotoksisiteye sahip olduğu bulunmuştur. PPH’ın yağ asidi profili GC-FID (gaz kromatografisi-alev iyonizasyon dedektörü) ve GC-MS (gaz kromatografisi-kütle spektrometresi) ile belirlenmiş ve majör yağ asitleri palmitik (%41.40±0.03), linoleik (%21.53±0.01), oleik (%12.06±0.01) ve stearik (%8.20±0.01) asit olarak kaydedilmiştir. PPM ve PPW ekstreleri, sıvı-sıvı ekstraksiyon tekniği kullanılarak fraksiyonlandırılmıştır. Tüm fraksiyonlar arasında metanol ekstresinden elde edilen 2-bütanol fraksiyonu (PPM-B) PC3 ve 3T3 hücre hatlarında en iyi sitotoksisiteyi göstermiştir. Ayrıca, PPM’den izole edilen bileşiklerden (dioktil ftalat (1), ergosterol peroksit (2) ve pinoresinol (3)), ergosterol peroksit (2) 95.47±1.01 µg/mL olan IC50 değeri ile PC3 hücre hattında orta derecede sitotoksik olarak bulunmuştur. P. pini'nin prostat kanseri üzerindeki etkisinin ilk kez incelendiği bu çalışmada, türün sitotoksik özellikleri ortaya çıkartılarak tıbbi önemi kanıtlanmıştır.

Anahtar Kelimeler

• Porodaedalea pini
• Prostat kanseri
• Ekstre
• Yağ asidi
• İzolasyon

Kaynakça

1. Blagodatski, A., Yatsunskaya, M., Mikhailova, V., Tiasto, V., Kagansky, A. and Katanaev, V.L. (2018). Medicinal Mushrooms as An Attractive New Source of Natural Compounds for Future Cancer Therapy. Oncotarget, 9, 29259-29274.
2. Calder, P. C. (2015). Functional Roles of Fatty Acids and Their Effects on Human Health. J. Parenter. Enteral. Nutr., 39 (1 Suppl), 18-32.
3. Chen, M. and Huang, J. (2019). The Expanded Role of Fatty Acid Metabolism in Cancer: New Aspects and Targets. Precis. Clin. Med., 2 (3), 183-191.
4. Chen, Z., Bishop, K. S., Tanambell, H., Buchanan, P., Smith, C. and Quek, S. Y. (2019). Characterization of the bioactivities of an ethanol extract and some of its constituents from the New Zealand native mushroom Hericium novae-zealandiae. Food Funct., 10, 6633-6643.
5. Chin, Y. W., Jones,W. P., Rachman, I., Riswan, S., Kardono, L. B. S., Chai, H. B., Farnsworth, N. R., Cordell, G.A., Swanson, S. M., Cassady, J. M. and Kinghorn, A. D. (2006). Cytotoxic Lignans from the Stems of Helicteres hirsuta Collected in Indonesia. Phytother. Res., 20, 62-65.
6. Chiu, H. H. and Kuo, C. H. (2020). Gas Chromatography-Mass Spectrometry-Based Analytical Strategies for Fatty Acid Analysis in Biological Samples. J.Food Drug Anal., 28, 60-73.
7. Çakmakçı, S. and Tahmas-Kahyaoğlu, D. (2012). Yağ Asitlerinin Sağlık ve Beslenme Üzerine Etkilerine Genel Bir Bakış. Akademik Gıda, 10 (1),103-113.
8. Çayan, F., Deveci, E., Tel-Çayan, G. and Duru, M. E. (2020). Chemometric Approaches for the Characterization of the Fatty Acid Composition of Seventeen Mushroom Species. Anal. Lett., 53, 2784-2798.

9. Daniyal, M., Siddiqui, Z. A., Akram, M., Asif, H., Sultana, S. and Khan, A. (2014). Epidemiology, Etiology, Diagnosis and Treatment of Prostate Cancer. Asian Pac. J. Cancer. Prev., 15 (22), 9575-9578.
10. Deng, K., Zhang, Y., Ren, Z., Xie, L., Peng, W. and Gan, B. (2011). Phellinus sp. by High-Performance Liquid Chromatography with Photodiode-Array Detection. J. Med. Plant. Res., 5 (13), 2816.
11. Deveci, E., Tel-Çayan, G., Duru, M.E. and Öztürk, M. (2019b). Chemical Constituents of Porodaedalea pini Mushroom with Cytotoxic, Antioxidant and Anticholinesterase Activities. J. Food Meas. Charact., 13 (4), 2686-2695.
12. Deveci, E., Çayan, F., Tel‐Çayan, G. and Duru, M. E. (2019a). Structural Characterization and Determination of Biological Activities for Different Polysaccharides Extracted from Tree Mushroom Species. J. Food Biochem., 43 (9), e12965.
13. Deveci, E., Tel‐Çayan, G., Duru, M. E. and Öztürk, M. (2019c). Isolation, Characterization, and Bioactivities of Compounds from Fuscoporia torulosa Mushroom. J. Food Biochem., 43 (12), e13074.
14. Deveci, E., Tel-Çayan, G., Karakurt, S. and Duru, M. E. (2021). Cytotoxic Activities of Methanol Extract and Compounds of Porodaedalea pini Against Colorectal Cancer. Int. J. Second. Metab., 8 (1), 40-48.
15. Grönberg, H. (2003). Prostate Cancer Epidemiology. The Lancet, 361 (9360), 859-864.
16. Guo, J., Zhu, T., Collins, L., Xiao, Z. X., Kim, S. H. and Chen, C. Y. (2007). Modulation of Lung Cancer Growth Arrest and Apoptosis by Phellinus linteus. Mol. Carcinog., 46, 144-154.
17. Hanahan, D. and Weinberg, R.A. (2011). Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674.
18. Hao, Y.F. and Jiang, J.G. (2015). Origin and Evolution of China Pharmacopoeia and Its Implication for Traditional Medicines. Mini Rev. Med. Chem., 15, 595-603.
19. Hong, Y., Jang, A., Jang, H. and Yang, K. (2012). Inhibition of Nitric Oxide Production, iNOS and COX-2 Expression of Ergosterol Derivatives from Phellinus pini. Nat. Prod. Sci., 18, 147-152.
20. Hsing, A. W. and Chokkalingam, A. P. (2006). Prostate Cancer Epidemiology. Front. Biosci., 11(5), 1388-1413.
21. Jiang, J., Eliaz, I. and Sliva, D. (2011). Suppression of Growth and İnvasive Behavior of Human Prostate Cancer Cells by ProstaCaidTM: Mechanism of activity. Int. J. Oncol., 38, 1675-1682.
22. Kamalidehghan, B., Ghafouri-Fard, S., Motevaseli, E. and Ahmadipour, F. (2018). Inhibition of Human Prostate Cancer (PC-3) Cells and Targeting of PC-3-derived Prostate Cancer Stem Cells with Koenimbin, A Natural Dietary Compound from Murraya koenigii (L) Spreng. Drug Des. Dev. Ther., 12, 1119-1133.
23. Kim, S. H., Song, Y. S., Kim, S. K., Kim, B. C., Lim, C. J. and Park, E. H. (2004). Anti-inflammatory and Related Pharmacological Activities of the n-BuOH Subfraction of Mushroom Phellinus linteus. J. Ethnopharmacol., 93, 41-146.
24. Kroon, J., Metselaar, J.M., Storm, G. and van der Pluijm, G. (2014). Liposomal Nanomedicines in the Treatment of Prostate Cancer. Cancer Treat. Rev., 40, 578-584.
25. Lee, S. M., Kim, S. M., Lee, Y. H., Kim, W. J., Park, J. K., Park, Y., Jang, W. J., Shin, H. D. and Synytsya, A. (2010). Macromolecules isolated from Phellinus pini fruiting body: Chemical characterization and antiviral activity. Macromol. Res., 18, 602-609.
26. Lin, S. R., Chang, C. H., Hsu, C. F., Tsai, H. J., Cheng, H., Leong, M. K., Sung, P. J., Chen, J. C. and Weng, C. F. (2020). Natural Compounds as Potential Adjuvants to Cancer Therapy: Preclinical Evidence. Br. J. Pharmacol.,177, 1409-1423.
27. Ma, L., Chen, H., Dong, P. and Lu, X (2013). Anti-inflammatory and Anticancer Activities of Extracts and Compounds from the mushroom Inonotus obliquus. Food Chem., 139, 503-508.
28. Majolo, F., Delwing, L. K. O. B., Marmitt, D. J., Bustamante-Filho, I. C. and Goettert, M. I. (2019). Medicinal plants and Bioactive Natural Compounds for Cancer Treatment: Important Advances for Drug Discovery. Phytochem. Lett., 31, 196-207.
29. Nguyen, N. H., Ta, Q. T. H., Pham, Q. T., Luong, T. N. H., Phung, V. T., Duong, T. H. and Vo, V. G. (2020). Anticancer Activity of Novel Plant Extracts and Compounds from Adenosma bracteosum (Bonati) in Human Lung and Liver Cancer Cells. Molecules, 25, 2912.
30. Olennikov, D. N., Agafonova, S. V., Penzina, T. A. and Borovskii, G. B. (2014). Fatty Acid Composition of Fourteen Wood-decaying Basidiomycete Species Growing in Permafrost Conditions. Rec. Nat. Prod., 8:2, 184-188.
31. Popovic, V., Živković, J., Davidović, S., Stevanović, M. and Stojković, D. (2013). Mycotherapy of Cancer: An Update on Cytotoxic and Antitumor Activities of Mushrooms, Bioactive Principles and Molecular Mechanisms of Their Action. Curr. Top. Med. Chem.,13 (21), 2791-806.
32. Rawla, P. (2019). Epidemiology of Prostate Cancer. World J. Oncol., 10 (2), 63-89.
33. Reis, F. B., Barreira, J. C. M., Calhelha, R. C., van Griensven, L. J. I. D., Ciric, A., Gamoclija, J., Sokovic, M. and Ferreira, I. C. F. R. (2014). Chemical Characterization of the Medicinal Mushroom Phellinus linteus (Berkeley & Curtis) Teng and Contribution of Different Fractions to Its Bioactivity. Food Sci. Technol., 58, 478-485.
34. Sepporta, M. V., Mazza, T., Morozzi, G. and Fabiani. R. (2013). Pinoresinol Inhibits Proliferation and Induces Differentiation on Human HL60 Leukemia Cells. Nutr. Cancer, 65:8, 1208-1218.
35. Sesli, E., Asan, A. and Selçuk, F. (eds.). Abacı Günyar, Ö., Akata, I., Akgül, H., Aktaş, S., Alkan, S., Allı, H., Aydoğdu, H., Berikten, D., Demirel, K., Demirel, R., Doğan, H.H., Erdoğdu, M., Ergül, C.C., Eroğlu, G., Giray, G., Halikî Uztan, A., Kabaktepe, Ş., Kadaifçiler, D., Kalyoncu, F., Karaltı, İ., Kaşık, G., Kaya, A., Keleş, A., Kırbağ, S., Kıvanç, M., Ocak, İ., Ökten, S., Özkale, E., Öztürk, C., Sevindik, M., Şen, B., Şen, İ., Türkekul, İ., Ulukapı, M., Uzun, Ya., Uzun, Yu.,Yoltaş, A. (2020). Türkiye Mantarları Listesi. İstanbul: Ali Nihat Gökyiğit Vakfı Yayınları.
36. Sulkowska-Ziaja, K., Balik, M. and Muszyńska, B. (2021). Selected Species of the Genus Phellinus–Chemical Composition, Biological Activity, and Medicinal Applications. Chem. Biodivers., 18, e2100609.
37. Sumanasuriya, S. and De Bono, J. (2018). Treatment of Advanced Prostate Cancer-A Review of Current Therapies and Future Promise. Cold Spring Harb. Perspect. Med., 8 (6), a030635.
38. Tilaoui, M., Mouse, H.A. and Zyad, A. (2021). Update and New Insights on Future Cancer Drug Candidates From Plant-Based Alkaloids. Front. Pharmacol., 12, 719694.
39. Tokur, O. and Aksoy, A. (2017). In Vitro Cytotoxicity Assays. Harran Üniv. Vet. Fak. Derg., 6 (1), 112-118.
40. Tsuji, T., Du, W., Nishioka, T., Chen, L., Yamamoto, D. and Chen, C. Y. (2010). Phellinus linteus Extract Sensitizes Advanced Prostate Cancer Cells to Apoptosis in Athymic Nude Mice. PLoS One, 5, E9885.
41. Woyengo, T. A., Ramprasath, V. R. and Jones, P. J. H. (2009). Anticancer Effects of Phytosterols. Eur. J. Clin. Nutr., 63, 813-820.
42. Wu, Z., Zhang, Q., Li, N., Pu, Y., Wang, B. and Zhang, T. (2017). Comparison of Critical Methods Developed for Fatty Acid Analysis: A Review. J. Sep. Sci., 40, 288-298.
43. Xu, T. T., Beelman, R. B. and Lambert, J.D. (2012). The Cancer Preventive Effects of Edible Mushrooms. Anti-Cancer Agents Med. Chem., 12, 1255-1263.
44. Zhang, H., Shao, Q., Wang, W., Zhang, J., Zhang, Z., Liu, Y. and Yang, Y. (2017). Characterization of Compounds with Tumor–Cell Proliferation Inhibition Activity from Mushroom (Phellinus baumii) Mycelia Produced by Solid-State Fermentation. Molecules, 22, 698.
45. Zhang, Z., Zhou, L., Xie, N., NiceNice, E. C., Zhang, T., Cui, Y. and Huang, C. (2020). Overcoming Cancer Therapeutic Bottleneck by Drug Repurposing. Signal. Transduct. Target. Ther., 5 (1), 113-125.
46. Zhu, S., Jiao, W., Xu, Y., Hou, L., Li, H., Shao, J., Zhang, X., Wang, R. and Kong, D. (2021). Palmitic Acid İnhibits Prostate Cancer Cell Proliferation and Metastasis by Suppressing the PI3K/Akt Pathway. Life Sci., 286, 120046.
47. Zhu, T., Guo, J., Collins, L., Kelly, J., Xiao, Z. J., Kim, S. H. and Chen, C. Y. (2007). Phellinus linteus Activates Different Pathways to İnduce Apoptosis in Prostate Cancer Cells. Br. J. Cancer, 96, 583-590.