Biosynthesis of Dolastatin 10 in Marine Cyanobacteria, a Prototype for Multiple Approved Cancer Drugs

Kallifidas, Dimitris; Dhakal, Dipesh; Chen, Manyun; Chen, Qi-Yin; Kokkaliari, Sofia; Colon Rosa, Nicole A.; Ratnayake, Ranjala; Bruner, Steven D.; Paul, Valerie J.; Ding, Yousong; Luesch, Hendrik

doi:10.1021/acs.orglett.3c04083

Cited by 4 publications

(1 citation statement)

References 29 publications

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“…The growth of marine microorganisms in a special environment produces a variety of secondary metabolites with special chemical structures [ 4 ]. Many secondary metabolites have a variety of pharmacological effects, such as antibacterial, anti-inflammatory, anti-tumour, or antiviral effects, so they have received extensive attention and application [ 5 , 6 , 7 ]. As a result, marine microbial secondary metabolites have become a very promising source of drug candidates [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway

Xu,

Cao,

Zhang

et al. 2024

Marine Drugs

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Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia (BPH) properties of avellanin A from Aspergillus fumigatus fungus in marine sediment samples collected in the Beibu Gulf of Guangxi Province in China. The antiproliferative effect and molecular mechanism of avellanin A were explored in testosterone propionate (TP)-induced RWPE-1 cells. The transcriptome results showed that avellanin A significantly blocked the ECM–receptor interaction and suppressed the downstream PI3K-Akt signalling pathway. Molecular docking revealed that avellanin A has a good affinity for the cathepsin L protein, which is involved in the terminal degradation of extracellular matrix components. Subsequently, qRT-PCR analysis revealed that the expression of the genes COL1A1, COL1A2, COL5A2, COL6A3, MMP2, MMP9, ITGA2, and ITGB3 was significantly downregulated after avellanin A intervention. The Western blot results also confirmed that it not only reduced ITGB3 and FAK/p-FAK protein expression but also inhibited PI3K/p-PI3K and Akt/p-Akt protein expression in the PI3K-Akt signalling pathway. Furthermore, avellanin A downregulated Cyclin D1 protein expression and upregulated Bax, p21WAF1/Cip1, and p53 proapoptotic protein expression in TP-induced RWPE-1 cells, leading to cell cycle arrest and inhibition of cell proliferation. The results of this study support the use of avellanin A as a potential new drug for the treatment of BPH.

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Section: Introductionmentioning

confidence: 99%

Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway

Xu,

Cao,

Zhang

et al. 2024

Marine Drugs

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Harnessing Leptolyngbya for antiproliferative and antimicrobial metabolites through lens of modern techniques: A review

Negi,

Nigam,

Singh

2024

Algal Research

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Metabolite profiling and bioactivity assessment of cyanobacteria from the Azores reveals unique producers of cytotoxic and lipid reducing compounds

Luz,

Gonçalves,

Vasconcelos

et al. 2024

Algal Research

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Biosynthesis of Dolastatin 10 in Marine Cyanobacteria, a Prototype for Multiple Approved Cancer Drugs

Abstract: Experimental details, bioinformatic analysis of biosynthetic genes, NMR data, MS data, and structural prediction and biochemical studies of DolJ (PDF)■ AUTHOR INFORMATION

Cited by 4 publications

References 29 publications

Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway

Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway

Harnessing Leptolyngbya for antiproliferative and antimicrobial metabolites through lens of modern techniques: A review

Metabolite profiling and bioactivity assessment of cyanobacteria from the Azores reveals unique producers of cytotoxic and lipid reducing compounds

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