Differential genotoxicity and cytotoxicity of phomoxanthone A isolated from the fungus Phomopsis longicolla in HL60 cells and peripheral blood lymphocytes

Pavão, Gabriel Brolio; Venâncio, Vinícius Paula; Oliveira, Ana Lígia Leandrini de; Hernandes, Lívia Cristina; Almeida, Mara Ribeiro; Antunes, Lusânia Maria Greggi; Debonsi, Hosana Maria

doi:10.1016/j.tiv.2016.08.010

Cited by 14 publications

(11 citation statements)

References 26 publications

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“…It is interesting that PXA was first identified as an antimalarial compound, revealing its strong antibiotic activity against the protozoan parasite Plasmodium falciparum, then against Mycobacterium tuberculosis and against two human cancer cells lines [1] Furthermore, its reported antibiotic activity has been investigated against the alga Chlorella fusca, the fungus Ustilago violacea, and the bacterium Bacillus megaterium. This broad range of activity against bacteria, protozoans, fungi, plants, and animal cells banned it as a specific antibiotic, promoting, on the other side, its anti-cancer profile, since it was more toxic against human cancer cells than non-cancer cells [2][3][4][5]. More recently, it has been enlightened that PXA might have an application as a tool in the study of mitochondrial membrane dynamics, particularly non-canonical mitochondrial fission and remodeling of the mitochondrial matrix.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, PXA was also an effective activator of natural killer cells, murine T lymphocytes, and macrophages, coding for a stimulation of the immune system together with its pro-apoptotic activity. This dual effect could help in counteracting resistance phenomena during chemotherapy [2,3]. More recently, PXA also displayed robust cytotoxicity against different solid tumor cells and their cisplatin-resistant sub-cells, with IC 50 values in the high nanomolar/low micromolar range, as in ovarian cancer and bladder cancer cell pairs [4].…”

Section: Introductionmentioning

confidence: 94%

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Carbamoyl-Phosphate Synthase 1 as a Novel Target of Phomoxanthone A, a Bioactive Fungal Metabolite

et al. 2020

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Phomoxanthone A, a bioactive xanthone dimer isolated from the endophytic fungus Phomopsis sp., is a mitochondrial toxin weakening cellular respiration and electron transport chain activity by a fast breakup of the mitochondrial assembly. Here, a multi-disciplinary strategy has been developed and applied for identifying phomoxanthone A target(s) to fully address its mechanism of action, based on drug affinity response target stability and targeted limited proteolysis. Both approaches point to the identification of carbamoyl-phosphate synthase 1 as a major phomoxanthone A target in mitochondria cell lysates, giving also detailed insights into the ligand/target interaction sites by molecular docking and assessing an interesting phomoxanthone A stimulating activity on carbamoyl-phosphate synthase 1. Thus, phomoxanthone A can be regarded as an inspiring molecule for the development of new leads in counteracting hyperammonemia states.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Carbamoyl-Phosphate Synthase 1 as a Novel Target of Phomoxanthone A, a Bioactive Fungal Metabolite

et al. 2020

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“…to have remarkable biosynthetic potential due to its production of six different antimicrobial compounds including a novel sesquiterpene. Endophytic Phomopsis longicolla isolated from marine algae Bostrychia radicans , has been reported for the production of phomoxanthone A (PhoA) with anticancer effect in HL60 cell lines (Pavão et al ). Hence biosynthetic potential of Phomopsis sp.…”

Section: Discussionmentioning

confidence: 99%

Endophytic Phomopsis sp. colonization in Oryza sativa was found to result in plant growth promotion and piperine production

Chithra

Jasim

Mathew

et al. 2017

Physiologia Plantarum

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Endophytic fungi have been reported to have the acquired ability to synthesize host plant specific medicinal natural products. Many fungi with such properties have been characterized and optimized for the conditions which favor maximal production of desired products. However, the inherent plant colonization property of promising endophytic fungi is least studied. Exploiting the transgenome functioning of these fungi have immense applications to add beneficial features to nonhost plants. In the present study, the endophytic fungus Phomopsis sp. isolated from Piper nigrum was confirmed for piperine production by HPLC and LCMS/MS. Further, the fungal isolate was studied for its colonization ability in Oryza sativa. Interestingly, the fungi treated plants were found to have significant plant growth enhancement when compared to the control. Further screening of extract from treated plants by HPLC and LCMS/MS resulted in the confirmation of presence of piperine. The observed result is extremely significant as it opens up novel applications of endophytic fungal colonization in taxonomically diverse plants.

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“…Интересные результаты сравнительно недавно были получены при тестировании противоопухолевых агентов природного происхождения. Так, при тестировании фомоксантона Асоединения, выделенного из эндофитного гриба Phomopsis longicolla, связанного с морскими водорослями Bostrychia radicans, с помощью L-CBMN и метода ДНК-комет были выявлены генотоксические и цитостатические эффекты действия этого соединения на опухолевые клетки HL60, но не на нативные лимфоциты крови человека [29].…”

Section: исследования генотоксических эффектов новых перспективных прunclassified

Estimating genotoxic effects of anticancer drugs using cytokinesis-block micronucleus assay on human lymphocytes

Минина

Буслаев

2019

Fundamentalʹnaâ i kliničeskaâ medicina

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Here we review the current experience of using cytokinesis-block micronucleus (CBMN) assay on cultures of human lymphocytes to evaluate genotoxic effects of anticancer drugs. Having performed search in PubMed, Scopus, Web of Science, TOXLINE, and the Cochrane Library, we identified a total of 172 relevant studies. Out of them, 89 were conducted in vitro, and 41 were published within the last decade. The mentioned studies concordantly demonstrated a significant increase in micronuclei, protrusions, nucleoplasmic bridges, and a decrease in proliferation in cells treated with anticancer drugs in a time- and dose-dependent manner. Notably, the results of CBMN assay are consistent with the data obtained from other cytogenetic techniques (comet assay, chromosomal aberration analysis, analysis of mutations in housekeeping genes, and fluorescence in situ hybridisation). Conclusion. CBMN assay permits a reliable evaluation of the mutagenic effects related to anticancer drugs.

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Differential genotoxicity and cytotoxicity of phomoxanthone A isolated from the fungus Phomopsis longicolla in HL60 cells and peripheral blood lymphocytes

Cited by 14 publications

References 26 publications

Carbamoyl-Phosphate Synthase 1 as a Novel Target of Phomoxanthone A, a Bioactive Fungal Metabolite

Carbamoyl-Phosphate Synthase 1 as a Novel Target of Phomoxanthone A, a Bioactive Fungal Metabolite

Endophytic Phomopsis sp. colonization in Oryza sativa was found to result in plant growth promotion and piperine production

Estimating genotoxic effects of anticancer drugs using cytokinesis-block micronucleus assay on human lymphocytes

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