Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines

Sabrina Adorisio, Alessandra Fierabracci, Isabella Muscari, Anna Marina Liberati, Lorenza Cannarile, Trinh Thi Thuy, Tran Van Sung, Hossain Sohrab, Choudhury Mahmood Hasan, Emira Ayroldi, Carlo Riccardi, Abdul Mazid, Domenico V Delfino

Research output: Contribution to journalArticle

Abstract

Cladosporium species are endophytic fungi that grow on organic matter and are considered food contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) and anhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium species residing inside Rauwolfia leaves. The impact of FUS and AFU on cell growth was assessed in acute myeloid leukemia (OCI-AML3) and other hematologic tumor cell lines (HL-60, U937, and Jurkat). Treatment with FUS or AFU reduced the number of OCI-AML3 cells as evaluated by a hemocytometer. Flow cytometry analyses showed that this effect was accompanied by diverse impairments in cell cycle progression. Specifically, FUS (20 or 10 μg/mL significantly decreased the percentage of cells in S phase and increased the percentage of cells in G2/M phase, whereas AFU increased the percentage of cells in G0/G1 phase (50 and 25 μg/mL) and decreased the percentage of cells in S (50 μg/mL) and G2/M (50 and 25 μg/mL) phases. Both substances significantly increased apoptosis at higher concentrations. The effects of FUS were more potent than those of AFU, with FUS up-regulating p21 expression in a p53-dependent manner, as detected by Western blot analyses, likely the consequence of decreased ERK phosphorylation and increased p38 expression (both of which increase p21 stability). FUS also decreased Akt phosphorylation and resulted in increased Fas ligand production and caspase-8/3-dependent apoptosis. These results suggest that FUS and AFU inhibit proliferation and increase apoptosis in cell lines derived from hematological cancers.

Original languageEnglish
JournalToxins
Volume11
Issue number9
DOIs
Publication statusPublished - Aug 29 2019

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Cladosporium
Cell growth
Cells
Cell Line
Growth
Neoplasms
Phosphorylation
Apoptosis
Tumors
Rauwolfia
Naphthoquinones
Cell Cycle Resting Phase
Column chromatography
Fas Ligand Protein
Flow cytometry
Caspase 8
G2 Phase
G1 Phase
Tumor Cell Line
Fungi

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Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines. / Adorisio, Sabrina; Fierabracci, Alessandra; Muscari, Isabella; Liberati, Anna Marina; Cannarile, Lorenza; Thuy, Trinh Thi; Sung, Tran Van; Sohrab, Hossain; Hasan, Choudhury Mahmood; Ayroldi, Emira; Riccardi, Carlo; Mazid, Abdul; Delfino, Domenico V.

In: Toxins, Vol. 11, No. 9, 29.08.2019.

Research output: Contribution to journalArticle

Adorisio, S, Fierabracci, A, Muscari, I, Liberati, AM, Cannarile, L, Thuy, TT, Sung, TV, Sohrab, H, Hasan, CM, Ayroldi, E, Riccardi, C, Mazid, A & Delfino, DV 2019, 'Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines', Toxins, vol. 11, no. 9. https://doi.org/10.3390/toxins11090503
Adorisio, Sabrina ; Fierabracci, Alessandra ; Muscari, Isabella ; Liberati, Anna Marina ; Cannarile, Lorenza ; Thuy, Trinh Thi ; Sung, Tran Van ; Sohrab, Hossain ; Hasan, Choudhury Mahmood ; Ayroldi, Emira ; Riccardi, Carlo ; Mazid, Abdul ; Delfino, Domenico V. / Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines. In: Toxins. 2019 ; Vol. 11, No. 9.
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abstract = "Cladosporium species are endophytic fungi that grow on organic matter and are considered food contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) and anhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium species residing inside Rauwolfia leaves. The impact of FUS and AFU on cell growth was assessed in acute myeloid leukemia (OCI-AML3) and other hematologic tumor cell lines (HL-60, U937, and Jurkat). Treatment with FUS or AFU reduced the number of OCI-AML3 cells as evaluated by a hemocytometer. Flow cytometry analyses showed that this effect was accompanied by diverse impairments in cell cycle progression. Specifically, FUS (20 or 10 μg/mL significantly decreased the percentage of cells in S phase and increased the percentage of cells in G2/M phase, whereas AFU increased the percentage of cells in G0/G1 phase (50 and 25 μg/mL) and decreased the percentage of cells in S (50 μg/mL) and G2/M (50 and 25 μg/mL) phases. Both substances significantly increased apoptosis at higher concentrations. The effects of FUS were more potent than those of AFU, with FUS up-regulating p21 expression in a p53-dependent manner, as detected by Western blot analyses, likely the consequence of decreased ERK phosphorylation and increased p38 expression (both of which increase p21 stability). FUS also decreased Akt phosphorylation and resulted in increased Fas ligand production and caspase-8/3-dependent apoptosis. These results suggest that FUS and AFU inhibit proliferation and increase apoptosis in cell lines derived from hematological cancers.",
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T1 - Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines

AU - Adorisio, Sabrina

AU - Fierabracci, Alessandra

AU - Muscari, Isabella

AU - Liberati, Anna Marina

AU - Cannarile, Lorenza

AU - Thuy, Trinh Thi

AU - Sung, Tran Van

AU - Sohrab, Hossain

AU - Hasan, Choudhury Mahmood

AU - Ayroldi, Emira

AU - Riccardi, Carlo

AU - Mazid, Abdul

AU - Delfino, Domenico V

PY - 2019/8/29

Y1 - 2019/8/29

N2 - Cladosporium species are endophytic fungi that grow on organic matter and are considered food contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) and anhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium species residing inside Rauwolfia leaves. The impact of FUS and AFU on cell growth was assessed in acute myeloid leukemia (OCI-AML3) and other hematologic tumor cell lines (HL-60, U937, and Jurkat). Treatment with FUS or AFU reduced the number of OCI-AML3 cells as evaluated by a hemocytometer. Flow cytometry analyses showed that this effect was accompanied by diverse impairments in cell cycle progression. Specifically, FUS (20 or 10 μg/mL significantly decreased the percentage of cells in S phase and increased the percentage of cells in G2/M phase, whereas AFU increased the percentage of cells in G0/G1 phase (50 and 25 μg/mL) and decreased the percentage of cells in S (50 μg/mL) and G2/M (50 and 25 μg/mL) phases. Both substances significantly increased apoptosis at higher concentrations. The effects of FUS were more potent than those of AFU, with FUS up-regulating p21 expression in a p53-dependent manner, as detected by Western blot analyses, likely the consequence of decreased ERK phosphorylation and increased p38 expression (both of which increase p21 stability). FUS also decreased Akt phosphorylation and resulted in increased Fas ligand production and caspase-8/3-dependent apoptosis. These results suggest that FUS and AFU inhibit proliferation and increase apoptosis in cell lines derived from hematological cancers.

AB - Cladosporium species are endophytic fungi that grow on organic matter and are considered food contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) and anhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium species residing inside Rauwolfia leaves. The impact of FUS and AFU on cell growth was assessed in acute myeloid leukemia (OCI-AML3) and other hematologic tumor cell lines (HL-60, U937, and Jurkat). Treatment with FUS or AFU reduced the number of OCI-AML3 cells as evaluated by a hemocytometer. Flow cytometry analyses showed that this effect was accompanied by diverse impairments in cell cycle progression. Specifically, FUS (20 or 10 μg/mL significantly decreased the percentage of cells in S phase and increased the percentage of cells in G2/M phase, whereas AFU increased the percentage of cells in G0/G1 phase (50 and 25 μg/mL) and decreased the percentage of cells in S (50 μg/mL) and G2/M (50 and 25 μg/mL) phases. Both substances significantly increased apoptosis at higher concentrations. The effects of FUS were more potent than those of AFU, with FUS up-regulating p21 expression in a p53-dependent manner, as detected by Western blot analyses, likely the consequence of decreased ERK phosphorylation and increased p38 expression (both of which increase p21 stability). FUS also decreased Akt phosphorylation and resulted in increased Fas ligand production and caspase-8/3-dependent apoptosis. These results suggest that FUS and AFU inhibit proliferation and increase apoptosis in cell lines derived from hematological cancers.

U2 - 10.3390/toxins11090503

DO - 10.3390/toxins11090503

M3 - Article

C2 - 31470629

VL - 11

JO - Toxins

JF - Toxins

SN - 2072-6651

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ER -