Cytotoxic effects of Fisturalin-3 and 11-Deoxyfisturalin-3 on Jurkat and U937 cell lines

Abstract

Background. Fisturalines are bromotyrosine compounds isolated from marine sponges. Previous studies have shown antineoplasic, antiviral and antibacterial effects in Vitro; however, the possible effects of these compounds in hematologic malignancies have not been assessed. Methods. In the present study, the antiproliferative and pro apoptotic effects of Fistularin-3 (F) and 11-Deoxyfistularin-3 (DF) were assessed using the MTT method and annexin V/propidium iodide by flow cytometry using the cell lines: Jurkat E6.1 and U937. In addition, the cell cycle was assessed by flow cytometry. Results. Inhibition of the proliferative response was concentration and time dependent. The IC50 of F was 7.39 and 8.10 M for Jurkat E6.1 and U937 respectively. At 24 and 48 h, in the U937 cell line, but not in the Jurkat cell line, both compounds induced up to 35% annexin V increase. Necrosis was not observed in any case. Compound F induced, in both cell lines, a decrease in the number of cells in the S phase and increase in the G0/G1 phase. In the Jurkat cell line only, there was an increase in the number of cells in the G2/M phase. Compound DF was not as effective as F. Conclusions. F is more active than DF in repressing the cell cycle and inducing apoptosis. Both compounds are potentially useful in the development of new drugs to treat hematologic malignancies.

Discovery and characterization of Isofistularin-3, a marine brominated alkaloid, as a new DNA demethylating agent inducing cell cycle arrest and sensitization to TRAIL in cancer cells

“…No mechanistic study has been conducted so far to investigate the anticancer activity of this molecule. Nevertheless, cytotoxic activity against HeLa cells has been reported for Iso-3 [ 17 ], and a cytostatic effect was reported for Iso-3 structural isomer fistularin-3, against hematological cancer lines [ 18 ], indicating potential benefits in the use of Iso-3 against cancer.…”

Synergistic AML Cell Death Induction by Marine Cytotoxin (+)-1(R), 6(S), 1’(R), 6’(S), 11(R), 17(S)-Fistularin-3 and Bcl-2 Inhibitor Venetoclax

“…Bromotyrosine derivatives comprise several biologically active molecules [23,24,27,59]. We previously showed that isofistularin-3 docked into the DNMT1 DNA-binding CXXC domain and inhibits in vitro DNMT1 activity [22].…”

“…Recently, we described the compound isofistularin-3 from Aplysina aerophoba to act as a cytostatic drug against a panel of cancer cell lines and sensitizes lymphoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) [22]. Fistularins are a family of sponge-derived brominated tyrosine found in various genera of sponges, comprising molecules with cytotoxic activity against cancer cells [23,24,25,26,27]. Recently, fistularin-3 was also recognized in cultures of the marine bacterium Pseudovibrio denitrificans Ab134 isolated from the sponge Arenosclera brasiliensis [28], which evokes a potential use of microorganisms for sustainable supplies of complex marine molecules in drug development.…”

Synthesis, Leishmanicidal, Trypanocidal, Antiproliferative Assay and Apoptotic Induction of (2-Phenoxypyridin-3-yl)naphthalene-1(2H)-one Derivatives

“…An Epics XL cytometer (Beckman Coulter, Indianapolis, IN, USA) was used for the analysis. Untreated cells were the negative controls, and doxorubicin (Dox) (1 µM), and quercetin (QC) (50 µM) were the positive controls [ 64 , 65 , 66 ]. Early apoptosis refers to annexin V expression, late apoptosis, the coexpression of annexin V and PI, and necrosis the sole expression of PI.…”