Kanserle Savaşta Doğal bir Güç: Tıbbi Mantarlardaki Hispolonun Anti-Kanser Etkileri

Yıl 2024, , 50 - 59, 30.04.2024

Elif Nisa Pak

https://doi.org/10.30708/mantar.1454931

Öz

Kanser ülkemizde ölüm nedenleri arasında ikinci sırada yer almaktadır ve dünya çapında önemli bir halk sağlığı sorunudur. Geçtiğimiz birkaç yıl içinde, özellikle besinlerden elde edilen doğal bileşikler birçok kanser önleyici ilaç ya da takviye olarak tanımlanmıştır. Fakat bunların çok azı ya ileri klinik deneylerdedir ya da terapötik kullanım için hâlihazırda onaylanmıştır. Hispolon, geleneksel olarak kanser tedavisi dâhil birçok hastalık tedavisinde kullanılan tıbbi mantar türlerinde karşımıza çıkan stirilpiron grubundan fenolik bir bileşiktir. Bu derlemede amacımız, hispolon bileşiğinin anti-kanser etkilerini ve bu etkilerin olası mekanizmalarını açıklamaktır. Biyoaktif doğal bileşik olan hispolonun, hücre döngüsünü durdurma, apoptotik, anti-proliferatif, tümör gerilemesi, anti-metastatik gibi mekanizmalar yoluyla anti-kanser etki gösterdiği bildirilmiştir. Hispolonla ilgili çalışmalar daha yeni ve mekanizmaları, toksisitesi tam olarak anlaşılmış değildir.
Ek olarak, nerdeyse tüm çalışmalar hücre düzeyindedir. Hispolonun, anti-kanser bir ilaç olarak ya da alternatif bir takviye olarak kullanımı için daha fazla klinik çalışmaya ihtiyaç vardır.

Anahtar Kelimeler

Tıbbi Mantarlar, Hispolon, Anti-kanser, Mekanizmalar

A Natural Power to Fight Cancer: Anti-Cancer Effects of Hispolone in Medicinal Mushrooms

Öz

Cancer is the second leading cause of death in our country and is an important public health problem worldwide. In the past few years, natural compounds, especially those derived from food, have been identified as many anti-cancer drugs or supplements. But very few of them are either in further clinical trials or already approved for therapeutic use. Hispolon is a phenolic compound from the styrylpyrrone group, which is found in medicinal mushrooms, which are traditionally used in the treatment of many diseases, including cancer treatment. Our aim in this review is to explain the anti-cancer effects of the hispolon compound and the possible mechanisms of these effects. It has been reported that hispolon, a bioactive natural compound, has anti-cancer effects through mechanisms such as cell cycle arrest, apoptotic, anti-proliferative, tumor regression, and anti-metastatic. Studies on Hispolone are new and its mechanisms and toxicity are not fully understood.
In addition, almost all studies are at the cellular level. More clinical studies are needed for the use of Hispolone as an anti-cancer drug or as an alternative supplement.

Anahtar Kelimeler

Medicinal Mushrooms, Hispolon, Anti-cancer, Mechanisms

Kaynakça

• A.A.Ali, N., Jansen, R., Pilgrim, H., Liberra, K., & Lindequist, U. (1996). Hispolon, a yellow pigment from Inonotus hispidus. Phytochemistry, 41(3), 927-929. https://doi.org/https://doi.org/10.1016/0031-9422(95)00717-2
• Al Saqr, A., Aldawsari, M. F., Alrbyawi, H., Poudel, I., Annaji, M., Mulabagal, V., Ramani, M. V., Gottumukkala, S., Tiwari, A. K., Dhanasekaran, M., Panizzi, P. R., Arnold, R. D., & Babu, R. J. (2020). Co-Delivery of Hispolon and Doxorubicin Liposomes Improves Efficacy Against Melanoma Cells. AAPS PharmSciTech, 21(8), 304. https://doi.org/10.1208/s12249-020-01846-2
• Al Saqr, A., Majrashi, M., Alrbyawi, H., Govindarajulu, M., Fujihashi, A., Gottumukkala, S., Poudel, I., Arnold, R. D., Babu, R. J., & Dhanasekaran, M. (2020). Elucidating the anti-melanoma effect and mechanisms of Hispolon. Life Sci, 256, 117702. https://doi.org/10.1016/j.lfs.2020.117702
• Arcella, A., Oliva, M. A., Sanchez, M., Staffieri, S., Esposito, V., Giangaspero, F., & Cantore, G. (2017). Effects of hispolon on glioblastoma cell growth. Environ Toxicol, 32(9), 2113-2123. https://doi.org/10.1002/tox.22419
• Balaji, N. V., Ramani, M. V., Viana, A. G., Sanglard, L. P., White, J., Mulabagal, V., Lee, C., Gana, T. J., Egiebor, N. O., Subbaraju, G. V., & Tiwari, A. K. (2015). Design, synthesis and in vitro cell-based evaluation of the anti-cancer activities of hispolon analogs. Bioorg Med Chem, 23(9), 2148-2158. https://doi.org/https://doi.org/10.1016/j.bmc.2015.03.002
• Bonelli, M., La Monica, S., Fumarola, C., & Alfieri, R. (2019). Multiple effects of CDK4/6 inhibition in cancer: From cell cycle arrest to immunomodulation. Biochem Pharmacol, 170, 113676. https://doi.org/10.1016/j.bcp.2019.113676
• Campos, M., Kool, M. M., Daminet, S., Ducatelle, R., Rutteman, G., Kooistra, H. S., Galac, S., & Mol, J. A. (2014). Upregulation of the PI3K/Akt pathway in the tumorigenesis of canine thyroid carcinoma. J Vet Intern Med, 28(6), 1814-1823. https://doi.org/10.1111/jvim.12435
• Carneiro, B. A., & El-Deiry, W. S. (2020). Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol, 17(7), 395-417. https://doi.org/10.1038/s41571-020-0341-y
• Chang, H. Y., Sheu, M. J., Yang, C. H., Lu, T. C., Chang, Y. S., Peng, W. H., Huang, S. S., & Huang, G. J. (2011). Analgesic effects and the mechanisms of anti-inflammation of hispolon in mice. Evid Based Complement Alternat Med, 2011, 478246. https://doi.org/10.1093/ecam/nep027
• Chen, W., He, F. Y., & Li, Y. Q. (2006). The apoptosis effect of hispolon from Phellinus linteus (Berkeley & Curtis) Teng on human epidermoid KB cells. J Ethnopharmacol, 105(1-2), 280-285. https://doi.org/10.1016/j.jep.2006.01.026
• Chen, W., Zhao, Z., Li, L., Wu, B., Chen, S. F., Zhou, H., Wang, Y., & Li, Y. Q. (2008). Hispolon induces apoptosis in human gastric cancer cells through a ROS-mediated mitochondrial pathway. Free Radic Biol Med, 45(1), 60-72. https://doi.org/10.1016/j.freeradbiomed.2008.03.013
• Chen, Y. C., Chang, H. Y., Deng, J. S., Chen, J. J., Huang, S. S., Lin, I. H., Kuo, W. L., Chao, W., & Huang, G. J. (2013). Hispolon from Phellinus linteus induces G0/G1 cell cycle arrest and apoptosis in NB4 human leukaemia cells. Am J Chin Med, 41(6), 1439-1457. https://doi.org/10.1142/S0192415X13500961
• Chen, Y. S., Lee, S. M., Lin, C. C., & Liu, C. Y. (2014). Hispolon decreases melanin production and induces apoptosis in melanoma cells through the downregulation of tyrosinase and microphthalmia-associated transcription factor (MITF) expressions and the activation of caspase-3, -8 and -9. Int J Mol Sci, 15(1), 1201-1215. https://doi.org/10.3390/ijms15011201
• Chethna, P., Iyer, S. S., Gandhi, V. V., Kunwar, A., Singh, B. G., Barik, A., Balaji, N. V., Ramani, M. V., Subbaraju, G. V., & Priyadarsini, K. I. (2018). Toxicity and Antigenotoxic Effect of Hispolon Derivatives: Role of Structure in Modulating Cellular Redox State and Thioredoxin Reductase. ACS Omega, 3(6), 5958-5970. https://doi.org/https://doi.org/10.1021/acsomega.8b00415
• Fan, H. C., Hsieh, Y. C., Li, L. H., Chang, C. C., Janouskova, K., Ramani, M. V., Subbaraju, G. V., Cheng, K. T., & Chang, C. C. (2020). Dehydroxyhispolon Methyl Ether, A Hispolon Derivative, Inhibits WNT/beta-Catenin Signaling to Elicit Human Colorectal Carcinoma Cell Apoptosis. Int J Mol Sci, 21(22). https://doi.org/10.3390/ijms21228839
• Fernando, M. D. M., Adhikari, A., Senathilake, N. H. K. S., Silva, E. D. d., Nanayakkara, C. M., Wijesundera, R. L. C., Soysa, P., & Silva, B. G. D. N. K. d. (2019). <i>In Silico</i> Pharmacological Analysis of a Potent Anti-Hepatoma Compound of Mushroom Origin and Emerging Role as an Adjuvant Drug Lead. Food and Nutrition Sciences, 10(11), 1313-1333. https://doi.org/10.4236/fns.2019.1011095
• Grundemann, C., Arnhold, M., Meier, S., Backer, C., Garcia-Kaufer, M., Grunewald, F., Steinborn, C., Klemd, A. M., Wille, R., Huber, R., & Lindequist, U. (2016). Effects of Inonotus hispidus Extracts and Compounds on Human Immunocompetent Cells. Planta Med, 82(15), 1359-1367. https://doi.org/10.1055/s-0042-111693
• Ho, H. Y., Ho, Y. C., Hsieh, M. J., Yang, S. F., Chuang, C. Y., Lin, C. W., & Hsin, C. H. (2017). Hispolon suppresses migration and invasion of human nasopharyngeal carcinoma cells by inhibiting the urokinase-plasminogen activator through modulation of the Akt signaling pathway. Environ Toxicol, 32(2), 645-655. https://doi.org/10.1002/tox.22266
• Hong, D., Park, M. J., Jang, E. H., Jung, B., Kim, N. J., & Kim, J. H. (2017). Hispolon as an inhibitor of TGF-beta-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-beta- Snail/Twist axis. Oncol Lett, 14(4), 4866-4872. https://doi.org/10.3892/ol.2017.6789
• Hsiao, P. C., Hsieh, Y. H., Chow, J. M., Yang, S. F., Hsiao, M., Hua, K. T., Lin, C. H., Chen, H. Y., & Chien, M. H. (2013). Hispolon induces apoptosis through JNK1/2-mediated activation of a caspase-8, -9, and -3-dependent pathway in acute myeloid leukemia (AML) cells and inhibits AML xenograft tumor growth in vivo. J Agric Food Chem, 61(42), 10063-10073. https://doi.org/10.1021/jf402956m
• Hsieh, M. J., Chien, S. Y., Chou, Y. E., Chen, C. J., Chen, J., & Chen, M. K. (2014). Hispolon from Phellinus linteus possesses mediate caspases activation and induces human nasopharyngeal carcinomas cells apoptosis through ERK1/2, JNK1/2 and p38 MAPK pathway. Phytomedicine, 21(12), 1746-1752. https://doi.org/10.1016/j.phymed.2014.07.013
• Hsin, M. C., Hsieh, Y. H., Wang, P. H., Ko, J. L., Hsin, I. L., & Yang, S. F. (2017). Hispolon suppresses metastasis via autophagic degradation of cathepsin S in cervical cancer cells. Cell Death Dis, 8(10), e3089. https://doi.org/10.1038/cddis.2017.459
• Huang, G. J., Deng, J. S., Huang, S. S., & Hu, M. L. (2011). Hispolon induces apoptosis and cell cycle arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK phosphorylation. J Agric Food Chem, 59(13), 7104-7113. https://doi.org/10.1021/jf201289e
• Huang, G. J., Yang, C. M., Chang, Y. S., Amagaya, S., Wang, H. C., Hou, W. C., Huang, S. S., & Hu, M. L. (2010). Hispolon suppresses SK-Hep1 human hepatoma cell metastasis by inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt and ERK signaling pathways. J Agric Food Chem, 58(17), 9468-9475. https://doi.org/10.1021/jf101508r
• Jang, E. H., Jang, S. Y., Cho, I. H., Hong, D., Jung, B., Park, M. J., & Kim, J. H. (2015). Hispolon inhibits the growth of estrogen receptor positive human breast cancer cells through modulation of estrogen receptor alpha. Biochem Biophys Res Commun, 463(4), 917-922. https://doi.org/10.1016/j.bbrc.2015.06.035
• Kim, J. H., Kim, Y. C., & Park, B. (2016). Hispolon from Phellinus linteus induces apoptosis and sensitizes human cancer cells to the tumor necrosis factor-related apoptosis-inducing ligand through upregulation of death receptors. Oncol Rep, 35(2), 1020-1026. https://doi.org/10.3892/or.2015.4440
• Kolch, W. (2000). Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem J, 351 Pt 2(Pt 2), 289-305.
• Kou, R. W., Du, S. T., Xia, B., Zhang, Q., Yin, X., & Gao, J. M. (2021). Phenolic and Steroidal Metabolites from the Cultivated Edible Inonotus hispidus Mushroom and Their Bioactivities. J Agric Food Chem, 69(2), 668-675. https://doi.org/10.1021/acs.jafc.0c06822
• Kuo, M. Y., Yang, W. T., Ho, Y. J., Chang, G. M., Chang, H. H., Hsu, C. Y., Chang, C. C., & Chen, Y. H. (2022). Hispolon Methyl Ether, a Hispolon Analog, Suppresses the SRC/STAT3/Survivin Signaling Axis to Induce Cytotoxicity in Human Urinary Bladder Transitional Carcinoma Cell Lines. Int J Mol Sci, 24(1). https://doi.org/10.3390/ijms24010138
• Lee, H. M., Hwang, K. A., & Choi, K. C. (2017). Diverse pathways of epithelial mesenchymal transition related with cancer progression and metastasis and potential effects of endocrine disrupting chemicals on epithelial mesenchymal transition process. Mol Cell Endocrinol, 457, 103-113. https://doi.org/10.1016/j.mce.2016.12.026
• Liao, K. F., Chiu, T. L., Chang, S. F., Wang, M. J., & Chiu, S. C. (2021). Hispolon Induces Apoptosis, Suppresses Migration and Invasion of Glioblastoma Cells and Inhibits GBM Xenograft Tumor Growth In Vivo. Molecules, 26(15). https://doi.org/10.3390/molecules26154497
• Lu, T. L., Huang, G. J., Lu, T. J., Wu, J. B., Wu, C. H., Yang, T. C., Iizuka, A., & Chen, Y. F. (2009). Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells. Food Chem Toxicol, 47(8), 2013-2021. https://doi.org/10.1016/j.fct.2009.05.023
• Masood, M., Rasul, A., Sarfraz, I., Jabeen, F., Liu, S., Liu, X., Wei, W., Li, J., & Li, X. (2019). Hispolon induces apoptosis against prostate DU145 cancer cells via modulation of mitochondrial and STAT3 pathways. Pak J Pharm Sci, 32(5(Supplementary)), 2237-2243.
• Palacio, M., Gutiérrez, Y., Franco-Molano, A. E., & Callejas-Posada, R. (2015). Nuevos registros de macrohongos (Basidiomycota) para Colombia procedentes de un bosque seco tropical. Actualidades Biológicas, 37(102), 319-339.
• Paul, M., Kumar Panda, M., & Thatoi, H. (2019). Developing Hispolon-based novel anticancer therapeutics against human (NF-kappabeta) using in silico approach of modelling, docking and protein dynamics. J Biomol Struct Dyn, 37(15), 3947-3967. https://doi.org/10.1080/07391102.2018.1532321
• Peluso, I., Yarla, N. S., Ambra, R., Pastore, G., & Perry, G. (2019). MAPK signalling pathway in cancers: Olive products as cancer preventive and therapeutic agents. Semin Cancer Biol, 56, 185-195. https://doi.org/10.1016/j.semcancer.2017.09.002
• Rossi, M., Caruso, F., Costanzini, I., Kloer, C., Sulovari, A., Monti, E., Gariboldi, M., Marras, E., Balaji, N. V., Ramani, M. V., & Subbaraju, G. V. (2019). X-ray crystal structures, density functional theory and docking on deacetylase enzyme for antiproliferative activity of hispolon derivatives on HCT116 colon cancer. Bioorg Med Chem, 27(17), 3805-3812. https://doi.org/10.1016/j.bmc.2019.07.008
• Sak, K. (2017). Epidemiological Evidences on Dietary Flavonoids and Breast Cancer Risk: A Narrative Review. Asian Pac J Cancer Prev, 18(9), 2309-2328. https://doi.org/https://doi.org/10.22034/apjcp.2017.18.9.2309
• Salvador-Montoya, C. A., Costa-Rezende, D. H., Ferreira-Lopes, V., Borba-Silva, M. A., & Popoff, O. F. (2018). Tropicoporus drechsleri (Hymenochaetales, Basidiomycota), a new species in the “Inonotus linteus” complex from northern Argentina. Phytotaxa, 338(1), 75-89.
• Sarfraz, A., Rasul, A., Sarfraz, I., Shah, M. A., Hussain, G., Shafiq, N., Masood, M., Adem, Ş., Sarker, S. D., & Li, X. (2020). Hispolon: A natural polyphenol and emerging cancer killer by multiple cellular signaling pathways. Environmental Research, 190, 110017. https://doi.org/https://doi.org/10.1016/j.envres.2020.110017
• Sesli, E., Asan, A. ve Selçuk, F. (edlr.) 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.
• Sun, Y. S., Zhao, Z., & Zhu, H. P. (2015). Hispolon inhibits TPA-induced invasion by reducing MMP-9 expression through the NF-kappaB signaling pathway in MDA-MB-231 human breast cancer cells. Oncol Lett, 10(1), 536-542. https://doi.org/10.3892/ol.2015.3220
• TÜİK. (2019). Ölüm Nedeni İstatistikleri. Retrieved Jun, 26 from https://data.tuik.gov.tr/Bulten/Index?p=Olum-ve-Olum-Nedeni-Istatistikleri-2019-33710
• Türkyılmaz, M., Hacıkamiloğlu, E., Baran Deniz, E., Boztaş, G., Dündar, S., Kavak Ergün, A., Sevinç, A., Tütüncü, S., & Atik, E. (2018). Türkiye kanser istatistikleri 2015. Türkiye Cumhuriyeti Sağlık Bakanlığı, Halk Sağlığı Genel Müdürlüğü, Ankara.
• Vivanco, I., & Sawyers, C. L. (2002). The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer, 2(7), 489-501. https://doi.org/10.1038/nrc839
• Voss, A. K., & Strasser, A. (2020). The essentials of developmental apoptosis. F1000Res, 9. https://doi.org/10.12688/f1000research.21571.1
• Wang, J., Hu, F., Luo, Y., Luo, H., Huang, N., Cheng, F., Deng, Z., Deng, W., & Zou, K. (2014). Estrogenic and anti-estrogenic activities of hispolon from Phellinus lonicerinus (Bond.) Bond. et sing. Fitoterapia, 95, 93-101. https://doi.org/10.1016/j.fitote.2014.03.007
• WHO. (2020). WHO report on cancer: setting priorities, investing wisely and providing care for all. Retrieved May, 2022 from https://www.who.int/publications/i/item/9789240001299
• Wu, Q., Kang, Y., Zhang, H., Wang, H., Liu, Y., & Wang, J. (2014). The anticancer effects of hispolon on lung cancer cells. Biochem Biophys Res Commun, 453(3), 385-391. https://doi.org/10.1016/j.bbrc.2014.09.098
• Yang, W. E., Chen, Y. T., Su, C. W., Chen, M. K., Yeh, C. M., Chen, Y. L., Tsai, M. Y., Yang, S. F., & Lin, C. W. (2023). Hispolon induces apoptosis in oral squamous cell carcinoma cells through JNK/HO-1 pathway activation. J Cell Mol Med, 27(9), 1250-1260. https://doi.org/10.1111/jcmm.17729
• Yin, R.-H., Zhao, Z.-Z., Chen, H.-P., Yin, X., Ji, X., Dong, Z.-J., Li, Z.-H., Feng, T., & Liu, J.-K. (2014). Tremulane sesquiterpenes from cultures of the fungus Phellinus igniarius and their vascular-relaxing activities. Phytochemistry Letters, 10, 300-303. https://doi.org/https://doi.org/10.1016/j.phytol.2014.10.019
• Yu, H., Lin, L., Zhang, Z., Zhang, H., & Hu, H. (2020). Targeting NF-kappaB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther, 5(1), 209. https://doi.org/10.1038/s41392-020-00312-6
• Yun, J. M., Min, K. J., & Kwon, T. K. (2019). Involvement of Up-regulation of Death Receptors and Bim in Hispolon-mediated TNF-related Apoptosis-inducing Ligand Sensitization in Human Renal Carcinoma. J Cancer Prev, 24(3), 155-162. https://doi.org/10.15430/JCP.2019.24.3.155
• Zhang, R.-q., Feng, X.-l., Wang, Z.-x., Xie, T.-c., Duan, Y., Liu, C., Gao, J.-m., & Qi, J. (2022). Genomic and Metabolomic Analyses of the Medicinal Fungus Inonotus hispidus for Its Metabolite’s Biosynthesis and Medicinal Application. Journal of Fungi, 8(12), 1245. https://www.mdpi.com/2309-608X/8/12/1245
• Zhao, Z., Sun, Y. S., Chen, W., Lv, L. X., & Li, Y. Q. (2016). Hispolon inhibits breast cancer cell migration by reversal of epithelial-to-mesenchymal transition via suppressing the ROS/ERK/Slug/E-cadherin pathway. Oncol Rep, 35(2), 896-904. https://doi.org/10.3892/or.2015.4445
• Zhu, L., Song, J., Zhou, J. L., Si, J., & Cui, B. K. (2019). Species Diversity, Phylogeny, Divergence Time, and Biogeography of the Genus Sanghuangporus (Basidiomycota). Front Microbiol, 10, 812. https://doi.org/10.3389/fmicb.2019.00812