Cellular responses induced in vitro by pestheic acid, a fungal metabolite, in a gastric adenocarcinoma cell line (PG100)

Abstract

ABSTRACT. There is a constant search for new cancer treatments that are less aggressive and economically affordable. In this context, natural products extracted from plants, fungi, and microorganisms are of great interest. Pestheic acid, or dihidromaldoxin, is a chlorinated diphenylic ether extracted from the phytopathogenic fungus Pestalotiopsis guepinii (Amphisphaeriaceae). We assessed the cytotoxic, cytostatic, and genotoxic effects of pestheic acid in a gastric adenocarcinoma cell line (PG100). A decrease in clonogenic survival was observed. Pestheic acid also induced significant increases in both micronucleus and nucleoplasmic bridge frequency. However, we did not observe changes in cell cycle kinetics or apoptosis induction. Reactive oxygen species induced by diphenylic ethers may explain the genotoxicity and mutagenicity of pestheic acid. The absence of repair checkpoints that we observed is probably due to the fact that the PG100 cell line lacks the TP53 gene, which is common in gastric cancers. Even though pestheic acid has had a clear cytotoxic effect, the minimal inhibitory concentration was high, which shows that pestheic acid is not an active anticancer compound under these conditions.

Naturally Occurring Asterric Acid Analogs: Chemistry and Biology

“…Thus, the authors summarized that the possible mechanism, pestheic acid ( 16 ), could enhance recombination or induce chromosomal aberrations by interfering with chromatin structure and/or the proteins. Moreover, they also proposed another possible mechanism to explain the genotoxic effects of polybrominated analogs that could create reactive oxygen species (ROS) to induce DNA damage …”

“…16 In 2013, Bahia et al assessed the cytotoxic, cytostatic, and genotoxic effects of pestheic acid (16) in a gastric adenocarcinoma cell line (PG100), and observed a decrease in clonogenic survival and significant increases in both micronucleus and nucleoplasmic bridge frequency but no changes in cell cycle kinetics or apoptosis induction. 71 Thus, the authors summarized that the possible mechanism, pestheic acid (16), could enhance recombination or induce chromosomal aberrations by interfering with chromatin structure and/ or the proteins. Moreover, they also proposed another possible mechanism to explain the genotoxic effects of polybrominated analogs that could create reactive oxygen species (ROS) to induce DNA damage.…”

“…Moreover, they also proposed another possible mechanism to explain the genotoxic effects of polybrominated analogs that could create reactive oxygen species (ROS) to induce DNA damage. 71 4.2. Antioxidant and Anti-inflammatory Activities.…”

Advances on anticancer fungal metabolites: sources, chemical and biological activities in the last decade (2012–2023)

“…The lack in PG100 cell line of the TP53 gene, which is common in gastric cancers, could determine the absence of repair checkpoints. Pestheic acid ( 29 ) showed clear cytotoxic effect but only at high concentration with a IC 50 of 50.5 μg/mL, which demonstrated that it is not a potent anticancer compound [ 45 ].

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Pestalotiopsis Diversity: Species, Dispositions, Secondary Metabolites, and Bioactivities

“…P. guepinii metabolites of ciprofloxacin and norfloxacin [96] culture broth extract inhibit actinomycete growth [97] pestheic acid or dihidromaldoxin genotoxicity and mutagenicity [98] alpha-pyrones [99] P. hainanensis taxol [19] caryophyllene-Type Sesquiterpenes [100] P. heterocorni 7-hydroxy-5-methoxy-4,6-dimethyl-7-O-α-L-rhamnosyl-phthalide and 7-hydroxy-5-methoxy-4,6-dimethyl-7-O-β-D-glucopyranosyl-phthalide [101] heterocornols A-L, methyl-(2-formyl-3-hydroxyphenyl) propanoate, cladoacetal A, xylarinol A, agropyrenol, vaccinol G, (R)-3-hydroxy-1-[(R)-4-hydroxy-1,3-dihydroisobenzofuran-1-yl]butan-2-one, and (R)-3-hydroxy-1-[(S)-4-hydroxy-1,3-dihydroisobenzo -furan-1-yl]butan-2-one cytotoxicity and antifungal [29] pestaloisocoumarins A and B, isopolisin B, pestalotiol A, gamahorin, pestalachloride B, pestalachloride E, pestalalactone atropisomers (8a/8b), cytotoxicity [30] heterocornols M and N, heterocornols O and P anticancer [28] P. humus pestynol antibacterial and antifungal activity, weak cytotoxicity [102] pestiocandin antibacterial and antifungal activity [103] P. jesteri jesterone and hydroxy-jesterone selective antimycotic activity [104] P. karstenii pestalrone A, pestalrone B, pestalotin, hydroxypestalotin cytotoxic activity, antiprotozoal activity [42] P. leucothës BS, GS, and YS Immunomodulatory [105] immunomodulatory effects [106] P. mangiferae 4-(2,4,7-trioxa-bicyclo [4.1.0] heptane-3-yl) phenol antibacterial and antifungal activity [107] P. microspora taxol antiproliferative activity [11,108] α-pyrone [109] (+)-dendocarbin L, (+)-sydonic acid, and (+)-sydowic acid cytotoxicity [68] isopestacin antifungal and antioxidant activities [110] pestalotiollide B [49,[111][112][113] pestalotiollide B, melanin [114] 7-epi-10-deacetyltaxol induces apoptosis [115] taxol, pestalotiollide B, 1, 8-dihydroxy naphthalene melanin antitumor [13] melanin [116]…”