Ophiobolin A Induces Autophagy and Activates the Mitochondrial Pathway of Apoptosis in Human Melanoma Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Dec 10

PMID 27936075

Citations 15

Authors

Carlo Rodolfo

Mariapina Rocco

Lucia Cattaneo

Maria Tartaglia

Mauro Sassi

Patrizia Aducci

Andrea Scaloni

Lorenzo Camoni

Mauro Marra

Affiliations

Soon will be listed here.

Abstract

Ophiobolin A, a fungal toxin from Bipolaris species known to affect different cellular processes in plants, has recently been shown to have anti-cancer activity in mammalian cells. In the present study, we investigated the anti-proliferative effect of Ophiobolin A on human melanoma A375 and CHL-1 cell lines. This cellular model was chosen because of the incidence of melanoma malignant tumor on human population and its resistance to chemical treatments. Ophyobolin A strongly reduced cell viability of melanoma cells by affecting mitochondrial functionality. The toxin induced depolarization of mitochondrial membrane potential, reactive oxygen species production and mitochondrial network fragmentation, leading to autophagy induction and ultimately resulting in cell death by activation of the mitochondrial pathway of apoptosis. Finally, a comparative proteomic investigation on A375 cells allowed to identify several Ophiobolin A down-regulated proteins, which are involved in fundamental processes for cell homeostasis and viability.

Citing Articles

Therapeutic Potential of Fungal Terpenes and Terpenoids: Application in Skin Diseases.

Trepa M, Sulkowska-Ziaja K, Kala K, Muszynska B Molecules. 2024; 29(5).

PMID: 38474692 PMC: 10934142. DOI: 10.3390/molecules29051183.

A Stereoselective Photoinduced Cycloisomerization Inspired by Ophiobolin A.

Law J, Callen D, Paola E, Gomes G, Frederich J Org Lett. 2022; 24(36):6499-6504.

PMID: 35944279 PMC: 10559756. DOI: 10.1021/acs.orglett.2c02272.

Physapruin A Induces Reactive Oxygen Species to Trigger Cytoprotective Autophagy of Breast Cancer Cells.

Yu T, Shiau J, Tang J, Yen C, Hou M, Cheng Y Antioxidants (Basel). 2022; 11(7).

PMID: 35883843 PMC: 9311569. DOI: 10.3390/antiox11071352.

The Surprising Story of Fusicoccin: A Wilt-Inducing Phytotoxin, a Tool in Plant Physiology and a 14-3-3-Targeted Drug.

Marra M, Camoni L, Visconti S, Fiorillo A, Evidente A Biomolecules. 2021; 11(9).

PMID: 34572605 PMC: 8470340. DOI: 10.3390/biom11091393.

Melatonin Induces Autophagy via Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress Pathway in Colorectal Cancer Cells.

Chok K, Koh R, Ng M, Ng P, Chye S Molecules. 2021; 26(16).

PMID: 34443626 PMC: 8400139. DOI: 10.3390/molecules26165038.

References

Myung J, Afjehi-Sadat L, Felizardo-Cabatic M, Slavc I, Lubec G . Expressional patterns of chaperones in ten human tumor cell lines. Proteome Sci. 2004; 2(1):8. PMC: 543454. DOI: 10.1186/1477-5956-2-8. View

Rho J, Roehrl M, Wang J . Glycoproteomic analysis of human lung adenocarcinomas using glycoarrays and tandem mass spectrometry: differential expression and glycosylation patterns of vimentin and fetuin A isoforms. Protein J. 2009; 28(3-4):148-60. DOI: 10.1007/s10930-009-9177-0. View

Ostergaard M, Hansen G, Vorum H, Honore B . Proteomic profiling of fibroblasts reveals a modulating effect of extracellular calumenin on the organization of the actin cytoskeleton. Proteomics. 2006; 6(12):3509-19. DOI: 10.1002/pmic.200500686. View

Beitner R . Detachment of glycolytic enzymes from cytoskeleton of melanoma cells induced by calmodulin antagonists. Eur J Pharmacol. 1997; 328(2-3):241-8. DOI: 10.1016/s0014-2999(97)83051-8. View

Chan T, Chen L, Guan X . Role of translationally controlled tumor protein in cancer progression. Biochem Res Int. 2012; 2012:369384. PMC: 3337558. DOI: 10.1155/2012/369384. View

Bury M, Girault A, Megalizzi V, Spiegl-Kreinecker S, Mathieu V, Berger W . Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity. Cell Death Dis. 2013; 4:e561. PMC: 3615734. DOI: 10.1038/cddis.2013.85. View

Ying L, Su D, Zhu J, Ma S, Katsaros D, Yu H . Genotyping of stathmin and its association with clinical factors and survival in patients with ovarian cancer. Oncol Lett. 2013; 5(4):1315-1320. PMC: 3629093. DOI: 10.3892/ol.2013.1144. View

Li Z, Min W, Gou J . Knockdown of cyclophilin A reverses paclitaxel resistance in human endometrial cancer cells via suppression of MAPK kinase pathways. Cancer Chemother Pharmacol. 2013; 72(5):1001-11. DOI: 10.1007/s00280-013-2285-8. View

Yang T, Lu Z, Meng L, Wei S, Hong K, Zhu W . The novel agent ophiobolin O induces apoptosis and cell cycle arrest of MCF-7 cells through activation of MAPK signaling pathways. Bioorg Med Chem Lett. 2011; 22(1):579-85. DOI: 10.1016/j.bmcl.2011.10.079. View

10.

Pastorino J, Hoek J . Regulation of hexokinase binding to VDAC. J Bioenerg Biomembr. 2008; 40(3):171-82. PMC: 2662512. DOI: 10.1007/s10863-008-9148-8. View

11.

Lu K, Finn G, Lee T, Nicholson L . Prolyl cis-trans isomerization as a molecular timer. Nat Chem Biol. 2007; 3(10):619-29. DOI: 10.1038/nchembio.2007.35. View

12.

Honore B, Vorum H . The CREC family, a novel family of multiple EF-hand, low-affinity Ca(2+)-binding proteins localised to the secretory pathway of mammalian cells. FEBS Lett. 2000; 466(1):11-8. DOI: 10.1016/s0014-5793(99)01780-9. View

13.

Ko J, Gu W, Lim I, Zhou T, Bang H . Expression profiling of mitochondrial voltage-dependent anion channel-1 associated genes predicts recurrence-free survival in human carcinomas. PLoS One. 2014; 9(10):e110094. PMC: 4198298. DOI: 10.1371/journal.pone.0110094. View

14.

McCommis K, Baines C . The role of VDAC in cell death: friend or foe?. Biochim Biophys Acta. 2011; 1818(6):1444-50. PMC: 3288473. DOI: 10.1016/j.bbamem.2011.10.025. View

15.

Kajita E, MORIWAKI J, Yatsuki H, Hori K, Miura K, Hirai M . Quantitative expression studies of aldolase A, B and C genes in developing embryos and adult tissues of Xenopus laevis. Mech Dev. 2001; 102(1-2):283-7. DOI: 10.1016/s0925-4773(01)00324-0. View

16.

Benbrook D, Long A . Integration of autophagy, proteasomal degradation, unfolded protein response and apoptosis. Exp Oncol. 2012; 34(3):286-97. View

17.

Ashkenazi A, Salvesen G . Regulated cell death: signaling and mechanisms. Annu Rev Cell Dev Biol. 2014; 30:337-56. DOI: 10.1146/annurev-cellbio-100913-013226. View

18.

Lv C, Qin W, Zhu T, Wei S, Hong K, Zhu W . Ophiobolin O isolated from Aspergillus ustus induces G1 arrest of MCF-7 cells through interaction with AKT/GSK3β/cyclin D1 signaling. Mar Drugs. 2015; 13(1):431-43. PMC: 4306945. DOI: 10.3390/md13010431. View

19.

Liu H, Peng H, Cheng Y, Yuan H, Yang-Yen H . Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP. Mol Cell Biol. 2005; 25(8):3117-26. PMC: 1069602. DOI: 10.1128/MCB.25.8.3117-3126.2005. View

20.

Murphy M . The HSP70 family and cancer. Carcinogenesis. 2013; 34(6):1181-8. PMC: 3670260. DOI: 10.1093/carcin/bgt111. View