3‐<i>O</i>‐methylfunicone produced by <i>penicillium pinophilum</i> affects cell motility of breast cancer cells, downregulating αvβ5 integrin and inhibiting metalloproteinase‐9 secretion

Buommino, Elisabetta; Boccellino, Mariarosaria; Filippis, Anna De; Petrazzuolo, Marcella; Cozza, Valentina; Nicoletti, Rosario; Ciavatta, Maria Letizia; Quagliuolo, Lucio; Tufano, Maria Antonietta

doi:10.1002/mc.20322

Cited by 30 publications

(28 citation statements)

References 36 publications

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“…There is a need to develop novel strategies for achieving additional means to control development and progression of breast cancer. In the search for novel anticancer agents against breast cancer with effective chemotherapeutic spectrum various research groups have been motivated to isolate and characterize natural compounds from fungal endophytes that will increase the number of these therapeutic tools to inhibit breast cancer cells proliferation [17]. In the present study, Cladosporol A, a potent, natural compound was isolated and purified from endophytic fungus Cladosporium cladosporioides isolated from Datura innoxia plant.…”

Section: Discussionmentioning

confidence: 99%

Cladosporol A triggers apoptosis sensitivity by ROS-mediated autophagic flux in human breast cancer cells

et al. 2017

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BackgroundEndophytes have proven to be an invaluable resource of chemically diverse secondary metabolites that act as excellent lead compounds for anticancer drug discovery. Here we report the promising cytotoxic effects of Cladosporol A (HPLC purified >98%) isolated from endophytic fungus Cladosporium cladosporioides collected from Datura innoxia. Cladosporol A was subjected to in vitro cytotoxicity assay against NCI60 panel of human cancer cells using MTT assay. We further investigated the molecular mechanism(s) of Cladosporol A induced cell death in human breast (MCF-7) cancer cells. Mechanistically early events of cell death were studied using DAPI, Annexin V-FITC staining assay. Furthermore, immunofluorescence studies were carried to see the involvement of intrinsic pathway leading to mitochondrial dysfunction, cytochrome c release, Bax/Bcl-2 regulation and flowcytometrically measured membrane potential loss of mitochondria in human breast (MCF-7) cancer cells after Cladosporol A treatment. The interplay between apoptosis and autophagy was studied by microtubule dynamics, expression of pro-apoptotic protein p21 and autophagic markers monodansylcadaverine staining and LC3b expression.ResultsAmong NCI60 human cancer cell line panel Cladosporol A showed least IC50 value against human breast (MCF-7) cancer cells. The early events of apoptosis were characterized by phosphatidylserine exposure. It disrupts microtubule dynamics and also induces expression of pro-apoptotic protein p21. Moreover treatment of Cladosporol A significantly induced MMP loss, release of cytochrome c, Bcl-2 down regulation, Bax upregulation as well as increased monodansylcadaverine (MDC) staining and leads to LC3-I to LC3-II conversion.ConclusionOur experimental data suggests that Cladosporol A depolymerize microtubules, sensitize programmed cell death via ROS mediated autophagic flux leading to mitophagic cell death.Graphical abstractThe proposed mechanism of Cladosporol A -triggered apoptotic as well as autophagic death of human breast cancer (MCF-7) cells. The figure shows that Cladosporol A induced apoptosis through ROS mediated mitochondrial pathway and increased p21 protein expression in MCF-7 cells in vitro. Electronic supplementary materialThe online version of this article (doi:10.1186/s12860-017-0141-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Cladosporol A triggers apoptosis sensitivity by ROS-mediated autophagic flux in human breast cancer cells

et al. 2017

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“…The soil fungus Penicillium pinophilum produces 3-Omethylfunicone (OMF), a secondary metabolite involved in the antagonistic behaviour against the plant pathogenic fungus Rhizoctonia solani [7,8]. Previous studies have demonstrated that OMF can induce the apoptotic pathway and inhibit cell motility in several tumour cell lines [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Cell-growth and migration inhibition of human mesothelioma cells induced by 3-O-Methylfunicone from Penicillium pinophilum and cisplatin

Buommino

Filippis

Nicoletti³

et al. 2011

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Malignant pleural mesothelioma is a fatal malignancy linked to asbestos exposure. The main challenge for mesothelioma treatment is to go beyond the drug resistance, in particular against cisplatin (CDDP), one of the most used chemotherapeutic drug. 3-O-methylfunicone (OMF) is a metabolite produced by the fungus Penicillium pinophilum; its antiproliferative properties have been previously studied in vitro. Particularly, OMF is able to inhibit mesothelioma cell motility. To improve the effects of CDDP by-passing the resistance of mesothelioma cells to this drug, in the present study we investigated the combined treatment of OMF with CDDP respectively in an established mesothelioma cell line (NCI) and primary mesothelioma cells (Mest). As compared to the effect of single treatments, the combination of OMF and CDDP resulted in a stronger inhibition of NCI and Mest cell proliferation. OMF combination with CDDP was also able to affect the migratory ability of NCI and Mest cells by down-regulating αv and β5 expression and reducing metalloproteinase 2 (MMP-2) production. In addition, this association was effective in modulating VEGF gene expression. This finding highlights the possibility to use OMF and CDDP together to regulate angiogenesis and tumour progression in mesothelioma.

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“…We have reported previously that decreased cell proliferation is also associated with inhibition of cell motility in breast cancer cells (7). To investigate if this was also the case in OMF‐treated NCI cells, a chemotaxis assay was performed.…”

Section: Resultsmentioning

confidence: 97%

“…We have shown previously that OMF can affect cell population growth of different tumour cell lines and induce apoptosis (6–8). In the present study, we investigated the effect of OMF on proliferation of NCI cells derived from human mesothelioma.…”

Section: Resultsmentioning

confidence: 99%

“…3‐ O ‐methylfunicone (OMF) is a secondary metabolite produced by the soil fungus Penicillium pinophilum (3) that has been found to antagonize growth of the plant pathogenic fungus Rhizoctonia solani (4). Previous studies carried out on cells of various tumour cell lines have demonstrated that OMF can induce the apoptotic pathway and inhibit cell motility (5–8).…”

Section: Introductionmentioning

confidence: 99%

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3‐O‐Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells

Buommino¹,

Paoletti²,

Filippis³

et al. 2010

Cell Proliferation

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3‐O‐methylfunicone produced by penicillium pinophilum affects cell motility of breast cancer cells, downregulating αvβ5 integrin and inhibiting metalloproteinase‐9 secretion

Cited by 30 publications

References 36 publications

Cladosporol A triggers apoptosis sensitivity by ROS-mediated autophagic flux in human breast cancer cells

Cladosporol A triggers apoptosis sensitivity by ROS-mediated autophagic flux in human breast cancer cells

Cell-growth and migration inhibition of human mesothelioma cells induced by 3-O-Methylfunicone from Penicillium pinophilum and cisplatin

3‐O‐Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells

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