Caspase-dependent signaling underlies glioblastoma cell death in response to the fungal metabolite, fusarochromanone

Mahdavian,Elahe; Marshall,Monique; Martin,Patrick  M.; Cagle,Patrice; Salvatore,Brian  A.; Quick,Quincy  A.

doi:10.3892/ijmm.2014.1842

Caspase-dependent signaling underlies glioblastoma cell death in response to the fungal metabolite, fusarochromanone

Authors:
- Elahe Mahdavian
- Monique Marshall
- Patrick M. Martin
- Patrice Cagle
- Brian A. Salvatore
- Quincy A. Quick
View Affiliations

Affiliations: Department of Chemistry and Physics, LSU-Shreveport, Shreveport, LA 71115, USA, Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA, Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA
Published online on: July 9, 2014 https://doi.org/10.3892/ijmm.2014.1842
Pages: 880-885

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Fungal metabolites continue to show promise as a viable class of anticancer agents. In the present study, we investigated the efficacy of the fungal metabolite, fusarochromanone (FC101), for its antitumor activities in glioblastomas, which have a median survival of less than two years and a poor clinical response to surgical resection, radiation therapy and chemotherapy. Using clinically applicable doses, we demonstrated that FC101 induced glioblastoma apoptotic cell death via caspase dependent signaling, as indicated by the cleavage of poly(ADP-ribose) polymerase, glioblastoma (PARP). FC101 also induced differential reactive oxygen species (ROS) levels in glioblastoma cells, contrasting a defined role of oxidative stress in apoptotic cell death observed with other fungal metabolites. Furthermore, the antitumorigenic effects of FC101 on tumor cell migration were assessed. Cell migration assays revealed that FC101 significantly reduced the migratory capacity of glioblastomas, which are incredibly invasive tumors. Taken together, the present study establishes FC101 as a candidate anticancer agent for the cooperative treatment of glioblastomas.

View Figures

View References

1	Wang LW, Zhang YL, Lin FC, Hu YZ and Zhang CL: Natural products with antitumor activity from endophytic fungi. Mini Rev Med Chem. 11:1056–1074. 2011. View Article : Google Scholar : PubMed/NCBI
2	Duncan MD, Harmon JW and Duncan LK: Actin disruption inhibits bombesin stimulation of focal adhesion kinase (pp125FAK) in prostate carcinoma. J Surg Res. 63:359–363. 1996. View Article : Google Scholar : PubMed/NCBI
3	Nomura M, Takahashi T, Uesugi A, Tanaka R and Kobayashi S: Inotodiol, a lanostane triterpenoid, from Inonotus obliquus inhibits cell proliferation through caspase-3-dependent apoptosis. Anticancer Res. 28:2691–2696. 2008.PubMed/NCBI
4	Handa N, Yamada T and Tanaka R: An unusual lanostane-type triterpenoid, spiroinonotsuoxodiol, and other triterpenoids from Inonotus obliquus. Phytochemistry. 14–15:1774–1779. 2010.PubMed/NCBI
5	Ma L, Chen H, Dong P and Lu X: Anti-inflammatory and anticancer activities of extracts and compounds from the mushroom Inonotus obliquus. Food Chem. 139:503–508. 2013. View Article : Google Scholar : PubMed/NCBI
6	Krogh P, Christensen DH, Hald B, Harlou B, Larsen C, Pedersen EJ and Thrane U: Natural occurrence of the mycotoxin fusarochromanone, a metabolite of Fusarium equiseti, in cereal feed associated with tibial dyschondroplasia. Appl Environ Microbiol. 55:3184–3188. 1989.PubMed/NCBI
7	Furmanski BD, Dréau D, Wuthier RE and Fuseler JW: Differential uptake and selective permeability of fusarochromanone (FC101), a novel membrane permeable anticancer naturally fluorescent compound in tumor and normal cells. Microsc Microanal. 15:545–557. 2009. View Article : Google Scholar
8	Dréau D, Foster M, Hogg M, Culberson C, Nunes P and Wuthier RE: Inhibitory effects of fusarochromanone on melanoma growth. Anticancer Drugs. 18:897–904. 2007.PubMed/NCBI
9	Bury M, Girault A, Mégalizzi V, et al: Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity. Cell Death Dis. 4:e5612013. View Article : Google Scholar : PubMed/NCBI
10	Stockmann-Juvala H, Mikkola J, Naarala J, Loikkanen J, Elovaara E and Savolainen K: Fumonisin B1-induced toxicity and oxidative damage in U-118MG glioblastoma cells. Toxicology. 202:173–183. 2004. View Article : Google Scholar : PubMed/NCBI
11	Stockmann-Juvala H, Mikkola J, Naarala J, Loikkanen J, Elovaara E and Savolainen K: Oxidative stress induced by fumonisin B1 in continuous human and rodent neural cell cultures. Free Radic Res. 9:933–942. 2004. View Article : Google Scholar : PubMed/NCBI
12	Stockmann-Juvala H, Naarala J, Loikkanen J, Vähäkangas K and Savolainen K: Fumonisin B1-induced apoptosis in neuroblastoma, glioblastoma and hypothalamic cell lines. Toxicology. 225:234–241. 2006. View Article : Google Scholar : PubMed/NCBI
13	Sen S, Dong M and Kumar S: Isoform-specific contributions of alpha-actinin to glioma cell mechanobiology. PLoS One. 4:e84272009. View Article : Google Scholar : PubMed/NCBI
14	Quick Q and Skalli O: Alpha-actinin 1 and alpha-actinin 4: contrasting roles in the survival, motility, and RhoA signaling of astrocytoma cells. Exp Cell Res. 316:1137–1147. 2010. View Article : Google Scholar : PubMed/NCBI
15	Bury M, Andolfi A, Rogister B, et al: Fusicoccin a, a phytotoxic carbotricyclic diterpene glucoside of fungal origin, reduces proliferation and invasion of glioblastoma cells by targeting multiple tyrosine kinases. Transl Oncol. 6:112–123. 2013. View Article : Google Scholar
16	Pommepuy I, Terro F, Petit B, et al: Brefeldin A induces apoptosis and cell cycle blockade in glioblastoma cell lines. Oncology. 4:459–467. 2003. View Article : Google Scholar : PubMed/NCBI
17	Chaudhari M, Jayaraj R, Bhaskar AS and Lakshmana Rao PV: Oxidative stress induction by T-2 toxin causes DNA damage and triggers apoptosis via caspase pathway in human cervical cancer cells. Toxicology. 262:153–161. 2009. View Article : Google Scholar
18	Acuña UM, Wittwer J, Ayers S, Pearce CJ, Oberlies NH and De Blanco EJ: Effects of (5Z)-7-oxozeaenol on MDA-MB-231 breast cancer cells. Anticancer Res. 32:2415–2421. 2012.PubMed/NCBI
19	Knudsen PB, Hanna B, Ohl S, et al: Chaetoglobosin A preferentially induces apoptosis in chronic lymphocytic leukemia cells by targeting the cytoskeleton. Leukemia. 28:1289–1298. 2014. View Article : Google Scholar : PubMed/NCBI
20	Buommino E, De Filippis A, Nicoletti R, et al: Cell-growth and migration inhibition of human mesothelioma cells induced by 3-O-methylfunicone from Penicillium pinophilum and cisplatin. Invest New Drugs. 30:1343–1351. 2012. View Article : Google Scholar : PubMed/NCBI
21	Rokkaku T, Kimura R, Ishikawa C, Yasumoto T, Senba M, Kanaya F and Mori N: Anticancer effects of marine carotenoids, fucoxanthin and its deacetylated product, fucoxanthinol, on osteosarcoma. Int J Oncol. 43:1176–1186. 2013.PubMed/NCBI