Network pharmacology-based study to identify the significant pathways of Lentinula edodes against cancer
Ki Kwang Oh
Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Korea
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft
Search for more papers by this authorMd Adnan
Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Korea
Contribution: Validation, Writing - review & editing
Search for more papers by this authorCorresponding Author
Dong Ha Cho
Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Korea
Correspondence
Dong Ha Cho, Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Korea.
Email: [email protected]
Contribution: Investigation, Supervision
Search for more papers by this authorKi Kwang Oh
Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Korea
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft
Search for more papers by this authorMd Adnan
Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Korea
Contribution: Validation, Writing - review & editing
Search for more papers by this authorCorresponding Author
Dong Ha Cho
Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Korea
Correspondence
Dong Ha Cho, Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Korea.
Email: [email protected]
Contribution: Investigation, Supervision
Search for more papers by this authorAbstract
Lentinula edodes (LE) is known as a good food source with potent anticancer efficacy, but its active chemical compounds and pathways against cancer have not been revealed. This study was to uncover the active chemical constituents and pathways of LE against cancer through network pharmacology. The chemical compositions were recognized by gas chromatography–mass spectrometry (GC–MS) and filtered drug-like compounds (DLCs) by SwissADME. Targets related to filtered compounds were recognized by two public databases and the final overlapping targets were identified by Venn diagram. Then, protein–protein interaction (PPI) and pathway-target-compound (PTC) networks were built by RStudio. Ultimately, we recognized the key compounds and targets via molecular docking test (MDT). A total of 33 compounds from LE were accepted by Lipinski's rule were selected as DLCs. The 33 compounds were associated with 108 targets and a key target (cyclooxygenase2 [COX2]) was identified through PPI networks. Most significantly, inactivation of pathways in cancer and activation of peroxisome proliferator activated receptor signaling pathway were significant pathways of LE. On MDT, we identified a key compound (Indole, 2-methyl-3-phenyl) on COX2 related to inactivation of athways in cancer, additionally, the number of 6 ergostane steroids was associated with the two pathways might be dual efficacy to alleviate inflammation against cancer. Overall, 13 targets, 11 compounds, and 2 key pathways of LE were identified as the significant elements to treat cancer. Hence, this study shows therapeutic evidence to verify the promising clinical effect of LE on cancer, suggesting that LE might be an important mushroom against cancer.
Practical applications
Lentinula edodes (LE) has been used widely in cuisine as well as alternative medicines, especially, for anticancer. The LE has rich nutritional compounds including proteins, vitamins, polyphenols, and glucans, however, most of which have a critical hurdle as poor bioavailability not to be applicable for pharmaceuticals. Its main cause is very hydrophilic property. Thus, we adopted GC–MS analysis to identify lipophilic compounds to enhance cell permeability involved in bioavailability. The compounds selected from LE were confirmed by Lipinski's rule for drug-like-compounds (DLCs). Then, we retrieved targets associated with DLCs, and multiple pathways, multiple targets, and multiple compounds against cancer on network-based analysis.
In summary, our study reveals the medicinal value of LE on cancer based on the multicomponents. Overall, the aim of this work is to represent the pharmacological evidence to reveal the therapeutic efficacy of AC on cancer, suggesting that DLCs from AC might be alleviators to dampen cancer.
CONFLICT OF INTEREST
The author has declared that no competing interests exist.
Open Research
DATA AVAILABILITY STATEMENT
All data generated or analyzed during this study are included in this published article (and its Supplementary Materials).
Supporting Information
Filename | Description |
---|---|
jfbc14258-sup-0001-TableS1.xlsxExcel 2007 spreadsheet , 19.4 KB |
Table S1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- Akmansu, M., Unsal, D., Bora, H., & Elbeg, S. (2006). Evaluation of nutritional status in cancer patients receiving radiotherapy influence of locoregional radiation treatment on tumor necrosis factor-a and interleukin-6 in the serum of patients with head and neck cancer. American Journal of Clinical Oncology, 29, 183–188. https://doi.org/10.1097/01.coc.0000198745.94757.ee
- Bommagani, S., Ponder, J., Penthala, N. R., Janganati, V., Jordan, C. T., Borrelli, M. J., & Crooks, P. A. (2017). Indole carboxylic acid esters of melampomagnolide B are potent anticancer agents against both hematological and solid tumor cells. European Journal of Medicinal Chemistry, 136, 393–405. https://doi.org/10.1016/J.EJMECH.2017.05.031
- Bong, A. H. L., & Monteith, G. R. (2018). Calcium signaling and the therapeutic targeting of cancer cells. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1865, 1786–1794. https://doi.org/10.1016/J.BBAMCR.2018.05.015
- Brown, H. A., Thomas, P. G., & Lindsley, C. W. (2017). Targeting phospholipase D in cancer, infection and neurodegenerative disorders. Nature Reviews Drug Discovery, 16, 351–367. https://doi.org/10.1038/nrd.2016.252
- Chen, H.-J., Hu, M.-H., Xu, F.-G., Xu, H.-J., She, J.-J., & Xia, H.-P. (2018). Understanding the inflammation-cancer transformation in the development of primary liver cancer. Hepatoma Research, 4, 29. https://doi.org/10.20517/2394-5079.2018.18
10.20517/2394?5079.2018.18 Google Scholar
- Choudhary, M. I., Yousuf, S., & Rahman, A. U. (2013). Withanolides: Chemistry and antitumor activity. Natural Products: Phytochemistry, Botany and Metabolism of Alkaloids, Phenolics and Terpenes, 5, 3465–3495. https://doi.org/10.1007/978-3-642-22144-6_150
10.1007/978?3?642?22144?6_150 Google Scholar
- Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420, 860–867. https://doi.org/10.1038/NATURE01322
- Daina, A., Michielin, O., & Zoete, V. (2017). Swiss ADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 1–13. https://doi.org/10.1038/srep42717
- Daina, A., Michielin, O., & Zoete, V. (2019). Swiss target prediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Research, 47, W357–W364. https://doi.org/10.1093/NAR/GKZ382
- Damiano, J. S., & Wasserman, E. (2013). Molecular pathways: Blockade of the PRLR signaling pathway as a novel antihormonal approach for the treatment of breast and prostate cancer. Clinical Cancer Research, 19, 1644–1650. https://doi.org/10.1158/1078-0432.CCR-12-0138
- Dandekar, D. S., Lopez, M., Carey, R. I., & Lokeshwar, B. L. (2005). Cyclooxygenase-2 inhibitor celecoxib augments chemotherapeutic drug-induced apoptosis by enhancing activation of caspase-3 and -9 in prostate cancer cells. International Journal of Cancer, 115, 484–492. https://doi.org/10.1002/IJC.20878
- Dannhardt, G., Kiefer, W., Krämer, G., Maehrlein, S., Nowe, U., & Fiebich, B. (2000). The pyrrole moiety as a template for COX-1/COX-2 inhibitors. European Journal of Medicinal Chemistry, 35, 499–510. https://doi.org/10.1016/S0223-5234(00)00150-1
- Davis, A., & Robson, J. (2016). The dangers of NSAIDs: Look both ways. The British Journal of General Practice, 66, 172–173. https://doi.org/10.3399/BJGP16X684433
- Düsterhöft, S., Lokau, J., & Garbers, C. (2019). The metalloprotease ADAM17 in inflammation and cancer. Pathology-Research and Practice, 215, 152410. https://doi.org/10.1016/J.PRP.2019.04.002
- Fang, F., Li, D., Zhao, L., Li, Y., Zhang, T., & Cui, B. (2019). Expression of NR1H3 in endometrial carcinoma and its effect on the proliferation of Ishikawa cells in vitro. Oncotargets and Therapy, 12, 685–697. https://doi.org/10.2147/OTT.S180534
- Finimundy, T. C., Gambato, G., Fontana, R., Camassola, M., Salvador, M., Moura, S., Hess, J., Henriques, J. A. P., Dillon, A. J. P., & Roesch-Ely, M. (2013). Aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exhibit high antioxidant capability and promising in vitro antitumor activity. Nutrition Research (New York, N.Y.), 33, 76–84. https://doi.org/10.1016/J.NUTRES.2012.11.005
- Grivennikov, S. I., Greten, F. R., & Karin, M. (2010). Immunity, inflammation, and cancer. Cell, 140, 883–899. https://doi.org/10.1016/J.CELL.2010.01.025
- Hashemi Goradel, N., Najafi, M., Salehi, E., Farhood, B., & Mortezaee, K. (2019). Cyclooxygenase-2 in cancer: A review. Journal of Cellular Physiology, 234, 5683–5699. https://doi.org/10.1002/JCP.27411
- Heberle, H., Meirelles, G. V., da Silva, F. R., Telles, G. P., & Minghim, R. (2015). InteractiVenn: A web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics, 16, 1–7. https://doi.org/10.1186/S12859-015-0611-3
- Hwang, Y.-J., Lee, E.-J., Kim, H.-R., & Hwang, K.-A. (2013). In vitro antioxidant and anticancer effects of solvent fractions from Prunella vulgaris var. lilacina. BMC Complementary and Alternative Medicine, 13, 310. https://doi.org/10.1186/1472-6882-13-310
- Jóźwiak, M., Filipowska, A., Fiorino, F., & Struga, M. (2020). Anticancer activities of fatty acids and their heterocyclic derivatives. European Journal of Pharmacology, 871, 172937. https://doi.org/10.1016/J.EJPHAR.2020.172937
- Kaur Gill, R., Om Kaushik, S., Chugh, J., Bansal, S., Shah, A., & Bariwal, J. (2014). Recent development in [1,4]benzodiazepines as potent anticancer agents: A review. Mini Reviews in Medicinal Chemistry, 14, 229–256. https://doi.org/10.2174/13895575113139990081
- Keiser, M. J., Roth, B. L., Armbruster, B. N., Ernsberger, P., Irwin, J. J., & Shoichet, B. K. (2007). Relating protein pharmacology by ligand chemistry. Nature Biotechnology, 25, 197–206. https://doi.org/10.1038/NBT1284
- Khanal, P., Patil, B. M., Chand, J., & Naaz, Y. (2020). Anthraquinone derivatives as an immune booster and their therapeutic option against COVID-19. Natural Products and Bioprospecting, 10, 325–335. https://doi.org/10.1007/S13659-020-00260-2
- Kim, J., Lee, J., Shin, C. M., Lee, D. H., & Park, B. J. (2015). Risk of gastrointestinal bleeding and cardiovascular events due to NSAIDs in the diabetic elderly population. BMJ Open Diabetes Research & Care, 3, e000133. https://doi.org/10.1136/BMJDRC-2015-000133
- Kong, W., Chen, N., Liu, T., Zhu, J., Wang, J., He, X., & Jin, Y. (2015). Large-scale transcriptome analysis of cucumber and botrytis cinerea during infection. PLoS One, 10, e0142221. https://doi.org/10.1371/JOURNAL.PONE.0142221
- Laskowski, R. A., & Swindells, M. B. (2011). LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery. Journal of Chemical Information and Modeling, 51, 2778–2786. https://doi.org/10.1021/CI200227U
- Leentjens, J., Quintin, J., Gerretsen, J., Kox, M., Pickkers, P., & Netea, M. G. (2014). The effects of orally administered Beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study. PLoS One, 9, e108794. https://doi.org/10.1371/JOURNAL.PONE.0108794
- Levin, J. I., Nelson, F. C., Santos, E. D., Du, M. T., MacEwan, G., Chen, J. M., Ayral-Kaloustian, S., Xu, J., Jin, G., Cummons, T., & Barone, D. (2004). Benzodiazepine inhibitors of the MMPs and TACE. Part 2. Bioorganic & Medicinal Chemistry Letters, 14, 4147–4151. https://doi.org/10.1016/J.BMCL.2004.06.031
- Li, W., Yuan, G., Pan, Y., Wang, C., & Chen, H. (2017). Network pharmacology studies on the bioactive compounds and action mechanisms of natural products for the treatment of diabetes mellitus: A review. Frontiers in Pharmacology, 0, 74. https://doi.org/10.3389/FPHAR.2017.00074
- Liu, B., Qu, L., & Yan, S. (2015). Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer Cell International, 15, 1–6. https://doi.org/10.1186/S12935-015-0260-7
- Lv, S., Wang, W., Wang, H., Zhu, Y., & Lei, C. (2019). PPARγ activation serves as therapeutic strategy against bladder cancer via inhibiting PI3K-Akt signaling pathway. BMC Cancer, 19, 1–13. https://doi.org/10.1186/S12885-019-5426-6
- Manavathi, B., Dey, O., Gajulapalli, V. N. R., Bhatia, R. S., Bugide, S., & Kumar, R. (2013). Derailed estrogen signaling and breast cancer: An authentic couple. Endocrine Reviews, 34, 1–32. https://doi.org/10.1210/ER.2011-1057
- Matsson, P., & Kihlberg, J. (2017). How big is too big for cell permeability? Journal of Medicinal Chemistry, 60, 1662–1664. https://doi.org/10.1021/ACS.JMEDCHEM.7B00237
- Modrak, D. E., Gold, D. V., & Goldenberg, D. M. (2006). Sphingolipid targets in cancer therapy. Molecular Cancer Therapeutics, 5, 200–208. https://doi.org/10.1158/1535-7163.MCT-05-0420
- Oh, K., Adnan, M., & Cho, D. (2021b). Uncovering mechanisms of Zanthoxylum piperitum fruits for the alleviation of rheumatoid arthritis based on network pharmacology. Biology, 10, 703. https://doi.org/10.3390/BIOLOGY10080703
- Oh, K.-K., Adnan, M., & Cho, D.-H. (2021a). Network pharmacology study to interpret signaling pathways of Ilex cornuta leaves against obesity. Processes, 9, 1106. https://doi.org/10.3390/PR9071106
- Oh, K. K., Adnan, M., Ju, I., & Cho, D. H. (2021). A network pharmacology study on main chemical compounds from Hibiscus cannabinus L. leaves. RSC Advances, 11, 11062–11082. https://doi.org/10.1039/D0RA10932K
- Patel, S., & Goyal, A. (2012). Recent developments in mushrooms as anti-cancer therapeutics: A review. 3. Biotech, 2, 1–15. https://doi.org/10.1007/S13205-011-0036-2
- Pinto, F. C. L., Almeida, J. G. L., Silveira, E. R., Costa, A. M., Guimarães, L. A., Wilke, D. V., Costa-Lotufo, L. V., Torres, M. C. M., & Pessoa, O. D. L. (2017). Steroids from the Brazilian zoanthids Palythoa caribaeorum and Palythoa variabilis. Journal of the Brazilian Chemical Society, 28, 485–491. https://doi.org/10.21577/0103-5053.20160323
- Platzer, B., Elpek, K. G., Cremasco, V., Baker, K., Stout, M. M., Schultz, C., Dehlink, E., Shade, K.-T. C., Anthony, R. M., Blumberg, R. S., Turley, S. J., & Fiebiger, E. (2015). IgE/FcεRI-mediated antigen cross-presentation by dendritic cells enhances anti-tumor immune responses. Cell Reports, 10, 1487–1495. https://doi.org/10.1016/J.CELREP.2015.02.015
- Posadzki, P., Watson, L. K., & Ernst, E. (2013). Adverse effects of herbal medicines: An overview of systematic reviews. Clinical Medicine, 13, 7–12. https://doi.org/10.7861/CLINMEDICINE.13-1-7
- Quintero-Fabián, S., Arreola, R., Becerril-Villanueva, E., Torres-Romero, J. C., Arana-Argáez, V., Lara-Riegos, J., Ramírez-Camacho, M. A., & Alvarez-Sánchez, M. E. (2019). Role of matrix metalloproteinases in angiogenesis and cancer. Frontiers in Oncology, 9, 1370. https://doi.org/10.3389/FONC.2019.01370
- Rahar, S., Swami, G., Nagpal, N., Nagpal, M. A., & Singh, G. S. (2011). Preparation, characterization, and biological properties of β-glucans. Journal of Advanced Pharmaceutical Technology & Research, 2, 94–103. https://doi.org/10.4103/2231-4040.82953
- Reka, A. K., Kurapati, H., Narala, V. R., Bommer, G., Chen, J., Standiford, T. J., & Keshamouni, V. G. (2010). Peroxisome proliferator-activated receptor-γ activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial-mesenchymal transition. Molecular Cancer Therapeutics, 9, 3221–3232. https://doi.org/10.1158/1535-7163.MCT-10-0570
- Roy, S., Rawat, A. K., Sammi, S. R., Devi, U., Singh, M., Gautam, S., Yadav, R. K., Rawat, J. K., Singh, L., Ansari, M. N., Saeedan, A. S., Pandey, R., Kumar, D., Kaithwas, G., Roy, S., Kumar Rawat, A., Raj Sammi, S., Devi, U., Singh, M., … Kaithwas, G. (2017). Alpha-linolenic acid stabilizes HIF-1 α and downregulates FASN to promote mitochondrial apoptosis for mammary gland chemoprevention. Oncotarget, 8, 70049–70071. https://doi.org/10.18632/ONCOTARGET.19551
- Saeed, N. M., El-Demerdash, E., Abdel-Rahman, H. M., Algandaby, M. M., Al-Abbasi, F. A., & Abdel-Naim, A. B. (2012). Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models. Toxicology and Applied Pharmacology, 264, 84–93. https://doi.org/10.1016/J.TAAP.2012.07.020
- Schwartz, B., & Hadar, Y. (2014). Possible mechanisms of action of mushroom-derived glucans on inflammatory bowel disease and associated cancer. Annals of Translational Medicine, 2, 9. https://doi.org/10.3978/J.ISSN.2305-5839.2014.01.03
- Sever, R., & Brugge, J. S. (2015). Signal transduction in cancer. Cold Spring Harbor Perspectives in Medicine, 5, 1–21. https://doi.org/10.1101/CSHPERSPECT.A006098
- Shityakov, S., & Förster, C. (2014). In silico predictive model to determine vector-mediated transport properties for the blood–brain barrier choline transporter. Advances and Applications in Bioinformatics and Chemistry: AABC, 7, 23–36. https://doi.org/10.2147/AABC.S63749
- Shurin, M. R. (2012). Cancer as an immune-mediated disease. ImmunoTargets and Therapy, 1, 1–6. https://doi.org/10.2147/ITT.S29834
- Stacker, S. A., & Achen, M. G. (2013). The VEGF signaling pathway in cancer: The road ahead. Chinese Journal of Cancer, 32, 297–302. https://doi.org/10.5732/CJC.012.10319
- Sukocheva, O., & Wadham, C. (2014). Role of sphingolipids in oestrogen signalling in breast cancer cells: An update. Journal of Endocrinology, 220, R25–R35. https://doi.org/10.1530/JOE-13-0388
- Szklarczyk, D., Gable, A. L., Lyon, D., Junge, A., Wyder, S., Huerta-Cepas, J., Simonovic, M., Doncheva, N. T., Morris, J. H., Bork, P., Jensen, L. J., & von Mering, C. (2019). STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Research, 47, D607–D613. https://doi.org/10.1093/NAR/GKY1131
- Tan, Z., Zhao, J.-L., Liu, J.-M., Zhang, M., Chen, R.-D., Xie, K.-B., Chen, D.-W., & Dai, J.-G. (2017). Lanostane triterpenoids and ergostane-type steroids from the cultured mycelia of Ganoderma capense. Journal of Asian Natural Products Research, 20, 844–851. https://doi.org/10.1080/10286020.2017.1399879
- Wagner, N., & Wagner, K.-D. (2020). PPARs and angiogenesis—Implications in pathology. International Journal of Molecular Sciences, 21, 1–23. https://doi.org/10.3390/IJMS21165723
- Wallace, J. L., Bak, A., McKnight, W., Asfaha, S., Sharkey, K. A., & MacNaughton, W. K. (1998). Cyclooxygenase 1 contributes to inflammatory responses in rats and mice: Implications for gastrointestinal toxicity. Gastroenterology, 115, 101–109. https://doi.org/10.1016/S0016-5085(98)70370-1
- Wang, D., & DuBois, R. N. (2006). Prostaglandins and cancer. Gut, 55, 115–122. https://doi.org/10.1136/GUT.2004.047100
- Wang, W., Yu, S., Huang, S., Deng, R., Ding, Y., Wu, Y., Li, X., Wang, A., Wang, S., Chen, W., & Lu, Y. (2019). A complex role for calcium signaling in colorectal cancer development and progression. Molecular Cancer Research, 17(11), 2145–2153. https://doi.org/10.1158/1541-7786.MCR-19-0429
- Weiss, C., Kinscherf, R., Roth, S., Friedmann, B., Fischbach, T., Reus, J., Droge, W., & Bartsch, P. (1995). Lymphocyte subpopulations and concentrations of soluble CD8 and CD4 antigen after anaerobic training. International Journal of Sports Medicine, 16, 117–121. https://doi.org/10.1055/S-2007-972976
- Wu, J., Wan, F., Sheng, H., Shi, G., Shen, Y., Lin, G., Dai, B., Zhu, Y., & Ye, D. (2017). NR1H3 expression is a prognostic factor of overall survival for patients with muscle-invasive bladder cancer. Journal of Cancer, 8, 852–860. https://doi.org/10.7150/JCA.17845
- Xiao, J., Gao, M., Fei, B., Huang, G., & Diao, Q. (2020). Nature-derived anticancer steroids outside cardica glycosides. Fitoterapia, 147, 104757. https://doi.org/10.1016/J.FITOTE.2020.104757
- Xu, C., Cheng, F., Chen, L., Du, Z., Li, W., Liu, G., Lee, P. W., & Tang, Y. (2012). In silico prediction of chemical Ames mutagenicity. Journal of Chemical Information and Modeling, 52, 2840–2847. https://doi.org/10.1021/CI300400A
- Yang, H., Lou, C., Sun, L., Li, J., Cai, Y., Wang, Z., Li, W., Liu, G., & Tang, Y. (2019). admetSAR 2.0: Web-service for prediction and optimization of chemical ADMET properties. Bioinformatics (Oxford, England), 35, 1067–1069. https://doi.org/10.1093/BIOINFORMATICS/BTY707
- Zhan, X., Qin, W., Wang, S., Zhao, K., Xin, Y., Wang, Y., Qi, Q., & Mao, Z. (2016). Synthesis and anti-cancer activity of 3-substituted Benzoyl-4-substituted phenyl-1H-pyrrole derivatives. Anti-Cancer Agents in Medicinal Chemistry, 17, 821–831. https://doi.org/10.2174/1871520616666160923092718
- Zhang, G. B., Li, Q. Y., Chen, Q. L., & Su, S. B. (2013). Network pharmacology: A new approach for Chinese herbal medicine research. Evidence-Based Complementary and Alternative Medicine, 2013, 1–10. https://doi.org/10.1155/2013/621423
- Zhang, J.-J., Li, Y., Zhou, T., Xu, D.-P., Zhang, P., Li, S., & Li, H.-B. (2016). Bioactivities and health benefits of mushrooms mainly from China. Molecules, 21, 1–16. https://doi.org/10.3390/MOLECULES21070938
- Zhang, Z., Wang, H., Wang, Q., Yan, M., Wang, H., Bi, C., Sun, S., & Fan, Y. (2016). Anticancer activity and computational modeling of ternary copper (II) complexes with 3-indolecarboxylic acid and 1,10-phenanthroline. International Journal of Oncology, 49, 691–699. https://doi.org/10.3892/IJO.2016.3542
- Zhou, Z., Qiao, J. X., Shetty, A., Wu, G., Huang, Y., Davidson, N. E., & Wan, Y. (2014). Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy. Cellular and Molecular Life Sciences: CMLS, 71, 1549.