Compounds isolated from the marine sea fan-derived fungus Neosartorya siamensis (KUFA 0017), namely, 2,4-dihydroxy-3-methylacetophenon (1), chevalone C (2), nortryptoquivaline (4), tryptoquivaline H (6), tryptoquivaline F (7), fiscalin A (8), epi-fiscalin A (9), epi-neofiscalin A (11) and epi-fiscalin C (13) were tested for anti-proliferative activity by MTT assay, DNA damage induction by comet assay, and induction of cell death by nuclear condensation assay on colon HCT116, liver HepG2 and melanoma A375 cancer cell lines. Compounds 2, 4, 8, 9, 11 and 13 presented IC values ranging from 24 to 153 μM in the selected cell lines. Cell death was induced in HCT116 by compounds 2, 4 and 8. In HepG2, compounds 4, 8, 9 and 11 were able to induce significant cell death. This induction of cell death is possibly not related to genotoxicity because none of the compounds induced significant DNA damage. These results suggest that selected compounds present an interesting anti-proliferative activity and cell death induction, consequently showing potential (specifically epi-fiscalin C) as future leads for chemotherapeutic agents. Further studies on mechanisms of action should ensue. Copyright © 2016 John Wiley & Sons, Ltd.

This study demonstrated, for the first time, that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2, HCT16 and A375 cells. The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.

No abstract

Doxorubicin (Dox) is one of the most successful anticancer drugs in use. However, chemoresistance is one of the main limitations that patients face. Therefore, development of new strategies to improve the efficacy of Dox is needed. Marine‐derived fungi are especially promising sources of new anticancer compounds. In this work, antitumor activity of crude ethyl extract of the cultures of the marine‐derived fungus Neosartorya siamensis KUFA 0017 (NS), combined with Dox, was evaluated in six cancer cell lines. To evaluate possible mechanisms involved in the eventual improvement of Dox's cytotoxicity by NS extract, effects on DNA damage, cell death, ultrastructural modifications, and intracellular accumulation of Dox were assessed. The NS extract demonstrated a significant enhancement of Dox's cytotoxic activity in A549 cells, inducing DNA damage, cell death, and intracellular accumulation of Dox. Additionally, the cytotoxic effect of eight compounds, isolated from this extract, that is, 2,4‐dihydroxy‐3‐methylacetophenone‐(C1), nortryptoquivaline‐(C2), chevalone C‐(C3), tryptoquivaline H‐(C4), fiscalin A‐(C5), epi‐fiscalin‐C (C6), epi‐neofiscalin A‐(C7), and epi‐fiscalin A‐(C8), alone and combined with Dox was also evaluated in lung cancer cells. The cytotoxic effect of Dox was potentiated by all the isolated compounds (except C1) in A549 cells. Therefore, we concluded that NS extract potentiated cytotoxicity by inhibiting cell proliferation, increasing intracellular accumulation of Dox, and inducing cell death (possibly by an autophagic process). The isolated compounds also enhanced the activity of Dox, supporting the potential of this sort of combination. These data call for further studies to characterize drug interactions and underlying mechanisms.

Background:The crude ethyl acetate extracts of marine-derived fungi Neosartorya tsunodae KUFC 9213 (E1) and N. laciniosa KUFC 7896 (E2), and soil fungus N. fischeri KUFC 6344 (E3) were evaluated for their in vitro anticancer activities on a panel of seven human cancer cell lines.Materials and Methods:The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed, after 48 h treatments with different concentrations of extracts, to determine their concentration of the extract or Dox that inhibits cell viability by 50% for each cell line. The effects of the crude extracts on DNA damage, clonogenic potential and their ability to induce cell death were also assessed.Results:E1 was found to the void of anti-proliferative effects. E2 was shown to decrease the clonogenic potential in human colorectal carcinoma cell line (HCT116), human malignant melanoma cell line (A375), human breast adenocarcinoma cell line (MCF7), and human caucasian colon adenocarcinoma Grade II cell line (HT29) cells, whereas E3 showed such effect only in HCT116 and MCF7 cells. Both extracts were found to increase DNA damage in some cell lines. E2 was found to induce cell death in HT29, HCT116, MCF7, and A375 cells while extract E3 increased cell death in MCF7 and HCT116 cell lines.Conclusion:The results reveal that E2 and E3 possess anticancer activities in human colon carcinoma, breast adenocarcinoma, and melanoma cells, validating the interest for an identification of molecular targets involved in the anticancer activity.SUMMARY The crude ethyl acetate extract of N. tsunodae (E1) did not decrease cell viability in any of the tested cell linesThe crude ethyl acetate extracts of N. laciniosa (E2) and N. fischeri (E3) decreased cell proliferation in some human cancer cell lines tested at both short- and long-termN. laciniosa (E2) induced a significant increase in the number of cell death, in part, due to the induction of DNA damageN. fischeri (E3) induce cell death but in some cell lines without induction of DNA damage detected by comet assayCrude ethyl extracts of N. laciniosa (E2) and N. fischeri (E3) exert an anticancer activity in human colon carcinoma, breast adenocarcinoma, and malignant melanoma cells. Abbreviations Used: A375: Human malignant melanoma cell line; A549: Human non-small lung cancer cell line; DAPI: 4,6-diamidino-2-phenylindole; DMEM: Dulbecco's Modified Eagle Medium; DMSO: Dimethylsulfoxide; Dox: Doxorubicin; E1: Neosartorya tsunodae KUFC 9213; E2: Neosartorya laciniosa KUFC 7896; E3: Neosartorya fischeri KUFC 6344; FBS: Fetal bovine serum; HCT116: Human colorectal carcinoma cell line; HEPES: (N-[2-hydroxyethyl] piperazine-N’-[2-ethane-sulfonic acid]); HepG2: Human hepatocellular carcinoma cell line; HT29: Human caucasian colon adenocarcinoma Grade II cell line; IC50: Concentration of the extract or Dox that inhibits cell viability by 50%; MCF7: Human breast adenocarcinoma cell line; MEM: Minimum Essential Medium Eagle; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NCI-H460: Human non-...

Background:Drug resistance is a major concern in the current chemotherapeutic approaches and the combination with natural compounds may enhance the cytotoxic effects of the anticancer drugs. Therefore, this study evaluated the cytotoxicity of crude ethyl extracts of six marine-derived fungi – Neosartorya tsunodae KUFC 9213 (E1), Neosartorya laciniosa KUFC 7896 (E2), Neosartorya fischeri KUFC 6344 (E3), Aspergillus similanensis KUFA 0013 (E4), Neosartorya paulistensis KUFC 7894 (E5), and Talaromyces trachyspermum KUFC 0021 (E6) – when combined with doxorubicin (Dox), in seven human cancer cell lines.Materials and Methods:The antiproliferative activity was primarily assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Results:Two extracts, E1 and E2, demonstrated a significant enhancement of Dox’s cytotoxicity in nonsmall cell lung cancer A549 cells. Accumulation of Dox in the nuclei increased when A549 cells were treated in combination with extracts E1 and E2, with induction of cell death observed by the nuclear condensation assay. The combination of E2 with Dox increased the DNA damage as detected by the comet assay. Ultrastructural observations by transmission electron microscopy suggest an autophagic cell death due to an increase of autophagic vesicles, namely with the combination of Dox with E1 and E2.Conclusion:These findings led to the conclusion that the fungal extracts E1 and E2 potentiate the anticancer action of Dox, through nuclear accumulation of Dox with induction of cell death mainly by cytotoxic autophagy.SUMMARYFungal extracts increase the cytotoxic activity of doxorubicin (Dox) in lung cancer cellsNuclear accumulation of Dox, DNA damage, and cell death as a mechanism of actionFungal extracts may potentiate the anticancer activity of conventional drugs.Abbreviations Used: A375: Human malignant melanoma cell line, A549: Human non small lung cancer cell line, DAPI: 4,6-Diamidino-2-phenylindole, DMEM: Dulbecco’s Modified Eagle Medium, DMSO: Dimethylsulfoxide, Dox: Doxorubicin, DSBs: DNA double-strand breaks, E1: Neosartorya tsunodae KUFC 9213, E2: Neosartorya laciniosa KUFC 7896, E3: Neosartorya fischeri KUFC 6344, E4: Aspergillus similanensis KUFA 0013, E5: Neosartorya paulistensis KUFC 7894, E6: Talaromyces trachyspermum KUFC 0021, FBS: Fetal bovine serum, HCT116: Human colorectal carcinoma cell line, HEPES: (N-[2-hydroxyethyl] piperazine-N’- [2-ethane-sulfonic acid]), HepG2: Human hepatocellular carcinoma cell line, HT29: Human Caucasian colon adenocarcinoma Grade II cell line, IC50: Concentration of the extract or Dox that inhibits cell viability by 50%, LRP: Lung resistance-related protein, MCF7: Human breast adenocarcinoma cell line, MEM: Minimum Essential Medium Eagle, MRPs: Multidrug resistance-associated proteins, MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, PBS: Phosphate-buffered saline, NSCLC: Nonsmall cell lung cancer, P-gp: P-glycoprotein, ROS: Reactive oxygen species, RPMI: Roswell Park Memorial Institute Medium, TEM: Transmission elec...

No abstract

No abstract