Cytotoxic Potential of Alternaria tenuissima AUMC14342 Mycoendophyte Extract: A Study Combined with LC-MS/MS Metabolic Profiling and Molecular Docking Simulation

Mousa, Amal A. Al; Abouelela, Mohamed E.; Hassane, Abdallah M. A.; Al-Khattaf, Fatimah S.; Hatamleh, Ashraf Atef; Alabdulhadi, Hadeel S.; Dahmash, Noura D.; Abo-Dahab, Nageh F.

doi:10.3390/cimb44100344

Cited by 5 publications

(2 citation statements)

References 72 publications

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“…For data analysis and interpretation, the software MSDIAL ver.5.1.230912 and MZmine 3 were utilized. The files of the raw data were then converted to mzXML format using MSConvert from the ProteoWizard suite (Al Mousa et al, 2022). 2.9 Computational investigation…”

Section: Metabolite Analysis Using Uhplc-ms/msmentioning

confidence: 99%

In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations

Al Awadh,

Sakagami,

Amano

et al. 2024

Front. Pharmacol.

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Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC50 = 51.8 and 40.1 μg/mL, respectively), which is relatively the same effect as 5-FU at CC50 = 69.4 μM and melphalan at CC50 = 36.3 μM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 μg/mL) exerted morphological changes and induced subG1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D (18) and O (12), and the flavonoid kaempferol (11). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera’s potential as an affordable source of therapeutic agents for a range of oral malignancies.

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Section: Metabolite Analysis Using Uhplc-ms/msmentioning

confidence: 99%

In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations

Al Awadh,

Sakagami,

Amano

et al. 2024

Front. Pharmacol.

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“…These metabolites may also include alkaloids, flavonoids, benzopyranones, phenolic acids, tannins, quinones, saponins, terpenoids, steroids, tetralones, xanthones, and many others [8]. The identified metabolites showed varied bioactivities with anticancer [9], antioxidative [10,11], antifungal [12,13], immunosuppressive [14], antiprotozoal [15], antiviral [16], and antibacterial efficiencies [17]. However, harmful influences can be caused by mycotoxins produced by some types of fungi [18,19].…”

Section: Introductionmentioning

confidence: 99%

Anti-Staphylococcal, Anti-Candida, and Free-Radical Scavenging Potential of Soil Fungal Metabolites: A Study Supported by Phenolic Characterization and Molecular Docking Analysis

Al Mousa,

Abouelela,

Al Ghamidi

et al. 2023

CIMB

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Staphylococcus and Candida are recognized as causative agents in numerous diseases, and the rise of multidrug-resistant strains emphasizes the need to explore natural sources, such as fungi, for effective antimicrobial agents. This study aims to assess the in vitro anti-staphylococcal and anti-candidal potential of ethyl acetate extracts from various soil-derived fungal isolates. The investigation includes isolating and identifying fungal strains as well as determining their antioxidative activities, characterizing their phenolic substances through HPLC analysis, and conducting in silico molecular docking assessments of the phenolics’ binding affinities to the target proteins, Staphylococcus aureus tyrosyl-tRNA synthetase and Candida albicans secreted aspartic protease 2. Out of nine fungal species tested, two highly potent isolates were identified through ITS ribosomal gene sequencing: Aspergillus terreus AUMC 15447 and A. nidulans AUMC 15444. Results indicated that A. terreus AUMC 15447 and A. nidulans AUMC 15444 extracts effectively inhibited S. aureus (concentration range: 25–0.39 mg/mL), with the A. nidulans AUMC 15444 extract demonstrating significant suppression of Candida spp. (concentration range: 3.125–0.39 mg/mL). The A. terreus AUMC 15447 extract exhibited an IC50 of 0.47 mg/mL toward DPPH radical-scavenging activity. HPLC analysis of the fungal extracts, employing 18 standards, revealed varying degrees of detected phenolics in terms of their presence and quantities. Docking investigations highlighted rutin as a potent inhibitor, showing high affinity (−16.43 kcal/mol and −12.35 kcal/mol) for S. aureus tyrosyl-tRNA synthetase and C. albicans secreted aspartic protease 2, respectively. The findings suggest that fungal metabolites, particularly phenolics, hold significant promise for the development of safe medications to combat pathogenic infections.

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Diversity of Alternaria‐derived toxins and their toxicodynamic and toxicokinetic characteristics in the food chain

Hussain,

Abbas,

Ali

et al. 2024

Food Frontiers

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The Alternaria genus comprises more than 250 fungal species among which pathogenic species cause diseases in economically important crops and contaminate food via secreted toxins. Among these host‐specific toxins (HSTs) generally harm specific plants, while certain non‐host‐specific toxins (nHSTs) have significant mutagenic and cytotoxic effects on humans and other vertebrates. Alternaria spp. tend to accumulate mycotoxins in food and food products, causing spoilage in fields during harvesting, postharvest stages, and storage. Changing climatic conditions and large cultivation areas led to a rise in Alternaria mycotoxins, with vegetarians being more frequently exposed. There is limited information on the toxicity incidence, absorption, excretion, and distribution of these mycotoxins in farms and domesticated animals; therefore, further investigation is required. This review covers current studies on the toxic effects of Alternaria mycotoxins, including genotoxicity, teratogenicity, nephrotoxicity, cytotoxicity, DNA damage, carcinogenicity, and immunosuppressive role. The toxicokinetic properties of these mycotoxins were explored, based on both in vitro and in vivo investigations. Combined effects of Alternaria mycotoxins with other mycotoxins in food are not well studied and can vary widely, showing synergistic, additive, or antagonistic interactions based on the specific combinations involved. The data presented here could strengthen risk assessment for Alternaria mycotoxins by emphasizing the need to minimize contact between contaminated and uncontaminated food and establish appropriate measures to ensure food safety.

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Cytotoxic Potential of Alternaria tenuissima AUMC14342 Mycoendophyte Extract: A Study Combined with LC-MS/MS Metabolic Profiling and Molecular Docking Simulation

Cited by 5 publications

References 72 publications

In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations

In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations

Anti-Staphylococcal, Anti-Candida, and Free-Radical Scavenging Potential of Soil Fungal Metabolites: A Study Supported by Phenolic Characterization and Molecular Docking Analysis

Diversity of Alternaria‐derived toxins and their toxicodynamic and toxicokinetic characteristics in the food chain

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