title: Recent progress in fungus-derived bioactive agents for targeting of signaling machinery in cancer cells.
abstract: It is becoming increasingly understood that tumor cells may have different mutations and dependencies on diverse intracellular signaling cascades for survival or metastatic potential. Overexpression of oncogenes, inactivation of tumor suppressor genes, genetic/epigenetic mutations, genomic instability, and loss of apoptotic cell death are some of the mechanisms that have been widely investigated in molecular oncology. We partition this multicomponent review into the most recent evidence on the anticancer activity of fungal substances obtained from in vitro and xenografted models, and these fungal substances modulate expression of oncogenic and tumor suppressor miRNAs. There are some outstanding questions regarding fungus-derived chemical-induced modulation of intracellular signaling networks in different cancer cell lines and preclinical models. Certain hints have emerged, emphasizing mechanisms via which apoptosis can be restored in TRAIL-resistant cancer cells. Reconceptualization of the knowledge obtained from these emerging areas of research will enable us to potentially identify natural agents with notable anticancer activity and minimal off-target effects. Integration of experimentally verified evidence obtained from cancer cell line gene expression with large-scale functional screening results and pharmacological sensitivity data will be helpful in identification of therapeutics with substantial efficacy. New tools and technologies will further deepen our understanding of the signaling networks that underlie the development of cancer, metastasis, and resistance to different therapeutics at both a personal and systems-wide level.
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xiukun
authors.initials: X
authors.lastname: Lin
authors.affiliation: Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.affiliation: Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ismail
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005658:Fungi / Q000737:chemistry*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents
keywords: apoptosis; cancer; cell signaling; fungal products; miRNA; xenograft
references.citation: PLoS One. 2012;7(3):e34406
references.pmid: 22470568
references.citation: Bioorg Med Chem. 2011 Aug 1;19(15):4644-51
references.pmid: 21741249
references.citation: Appl Microbiol Biotechnol. 2014 Nov;98(22):9389-98
references.pmid: 25176445
references.citation: Oncol Rep. 2013 Oct;30(4):1996-2002
references.pmid: 23921598
references.citation: Mar Drugs. 2013 Dec;11(12):5063-86
references.pmid: 24351905
references.citation: Arch Toxicol. 2015 Aug;89(8):1313-27
references.pmid: 25002221
references.citation: BMC Cancer. 2011;11:307
references.pmid: 21781302
references.citation: Food Chem. 2013 Feb 15;136(3-4):1213-9
references.pmid: 23194516
references.citation: Int J Environ Res Public Health. 2014 Feb;11(2):1855-72
references.pmid: 24514428
references.citation: Acta Otolaryngol Suppl. 1994;511:192-5
references.pmid: 7911266
references.citation: Oncol Rep. 2012 Dec;28(6):2016-22
references.pmid: 23023390
references.citation: J Ethnopharmacol. 2010 Feb 17;127(3):652-61
references.pmid: 19995598
references.citation: Cell Prolif. 2011 Oct;44(5):401-9
references.pmid: 21951283
references.citation: Invest New Drugs. 2009 Dec;27(6):491-502
references.pmid: 19009233
references.citation: World J Microbiol Biotechnol. 2014 Mar;30(3):1019-1025
references.pmid: 24122127
references.citation: Planta Med. 2013 Oct;79(15):1474-9
references.pmid: 24037588
references.citation: Cancer Sci. 2013 Nov;104(11):1476-82
references.pmid: 23952056
references.citation: FEBS Lett. 2014 Jun 5;588(12):2107-14
references.pmid: 24815696
references.citation: J Nat Prod. 2014 Apr 25;77(4):758-65
references.pmid: 24588135
references.citation: Drug Des Devel Ther. 2014;8:2555-602
references.pmid: 25548518
references.citation: J Agric Food Chem. 2012 Jul 25;60(29):7185-93
references.pmid: 22738037
references.citation: Cell Death Dis. 2013;4:e804
references.pmid: 24052072
references.citation: Cancer. 1986 Aug 15;58(4):865-72
references.pmid: 2941141
references.citation: Arch Pharm Res. 2014 Jul;37(7):839-44
references.pmid: 24078435
references.citation: Cell Prolif. 2010 Apr;43(2):114-23
references.pmid: 20447056
references.citation: PLoS One. 2013;8(12):e82751
references.pmid: 24358224
references.citation: J Agric Food Chem. 2013 Apr 17;61(15):3676-82
references.pmid: 23514335
references.citation: Carcinogenesis. 2013 Dec;34(12):2918-28
references.pmid: 23880305
references.citation: Br J Cancer. 2004 Mar 8;90(5):1003-10
references.pmid: 14997197
references.citation: Biol Pharm Bull. 2014;37(3):378-86
references.pmid: 24583858
references.citation: Cytokine. 2013 Jan;61(1):285-96
references.pmid: 23134667
references.citation: J Exp Clin Cancer Res. 2011;30:17
references.pmid: 21303527
references.citation: Anticancer Drugs. 2013 Aug;24(7):715-24
references.pmid: 23695013
references.citation: Phytomedicine. 2012 Jun 15;19(8-9):768-78
references.pmid: 22464013
references.citation: Biotechnol Lett. 2013 Sep;35(9):1395-403
references.pmid: 23690045
references.citation: Toxicol Appl Pharmacol. 2012 May 15;261(1):31-41
references.pmid: 22465936
references.citation: Chem Res Toxicol. 2011 Feb 18;24(2):238-45
references.pmid: 21158420
references.citation: Drug Des Devel Ther. 2014;8:1965-77
references.pmid: 25378909
references.citation: Int J Biol Macromol. 2013 Oct;61:97-101
references.pmid: 23831383
references.citation: Cancer Immunol Immunother. 1990;31(5):261-8
references.pmid: 2198088
references.citation: Cancer Biol Ther. 2014 Oct;15(10):1423-30
references.pmid: 25046358
references.citation: Exp Mol Med. 2011 Jan 31;43(1):24-34
references.pmid: 21150246
references.citation: J Med Food. 2013 Aug;16(8):681-91
references.pmid: 23957353
references.citation: Biochem Pharmacol. 2013 Jun 15;85(12):1727-40
references.pmid: 23603293
references.citation: PLoS One. 2013;8(9):e76320
references.pmid: 24086728
references.citation: PLoS One. 2013;8(2):e57431
references.pmid: 23468988
references.citation: Gynecol Oncol. 1995 Mar;56(3):412-20
references.pmid: 7705677
references.citation: Biomed Pharmacother. 1989;43(3):177-81
references.pmid: 2528386
references.citation: PLoS One. 2013;8(8):e71333
references.pmid: 23936501
references.citation: Nat Prod Commun. 2013 Oct;8(10):1431-4
references.pmid: 24354194
references.citation: Cell Signal. 2012 Apr;24(4):943-50
references.pmid: 22230687
references.citation: Biotherapy. 1991;3(4):287-95
references.pmid: 1786194
references.citation: Cancer Immunol Immunother. 2006 Apr;55(4):404-11
references.pmid: 16133112
references.citation: Medchemcomm. 2013 Oct;4(10):null
references.pmid: 24273638
references.citation: Leukemia. 2014 Jun;28(6):1289-98
references.pmid: 24280868