Crude Extracts of Marine-derived and Soil Fungi of the Genus Neosartorya Exhibit Selective Anticancer Activity by Inducing Cell Death in Colon, Breast and Skin Cancer Cell Lines

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

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-small lung cancer cell line; PBS: Phosphate buffered saline; PE: Plating efficiency; RPMI: Roswell park memorial institute medium; SF: Surviving fraction; U-251: Human malignant glioblastoma cell line.

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.

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.