Apoptosis induced by enniatins H and MK1688 isolated from Fusarium oxysporum FB1501.
Enniatins are cyclic peptides isolated from bacteria, fungi, and plants, with numerous biological effects on animal systems. Recently, we have reported that certain enniatins (ENs), such as EN H and EN MK1688, have cytotoxic effects on several adenocarcinoma cell lines. In an effort to understand the mechanism behind their cytotoxicity, we investigated whether ENs can induce apoptosis in human colorectal carcinoma cells (HCT-15 cells). Treatment with the ENs H and MK1688 resulted in an alteration of cellular and nuclear morphology, leading to an increase in the number of the cells with apoptotic nuclei (seen as condensed or fragmented nuclei). Furthermore, it was observed that cellular DNA fragmentation increased in a dose-dependent manner in EN treated cells. These cells have elevated activity levels for caspase-3, the enzyme responsible for initiating cell death, compared with the untreated cells. Normal caspase-3 activity levels were observed when Z-VAD-FMK, a caspase inhibitor, was added simultaneously with the ENs. Based on our results, we propose that the new ENs H and MK1688 induce cytotoxicity via an apoptotic pathway.
Hyun
Usok
U
Department of Biotechnology, Chung-Ang University, Kyunggi, Republic of Korea.
Lee
Dong-Hyun
DH
Lee
Chan
C
Shin
Cha-Gyun
CG
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D002449:Cell Aggregation / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D047630:Depsipeptides / Q000302:isolation & purification / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D005670:Fusarium / Q000737:chemistry*; D006801:Humans; D007202:Indicators and Reagents; D009183:Mycotoxins / Q000302:isolation & purification / Q000633:toxicity*
D000590:Amino Acid Chloromethyl Ketones; D000903:Antibiotics, Antineoplastic; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D047630:Depsipeptides; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; C543476:MK 1688; D009183:Mycotoxins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C543475:enniatin H; D053148:Caspase 3