Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived Aspergillus sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer Cells

Abstract

Marine-derived microorganisms are a valuable source of novel bioactive natural products. Asperphenin A is a lipopeptidyl benzophenone metabolite isolated from large-scale cultivation of marine-derived Aspergillus sp. fungus. The compound has shown potent antiproliferative activity against various cancer cells. However, the underlying mechanism of action remained to be elucidated. In this study, we demonstrated the antitumor activity and molecular mechanism of asperphenin A in human colon cancer cells for the first time. Asperphenin A inhibited the growth of colon cancer cells through G2/M cell cycle arrest followed by apoptosis. We further discovered that asperphenin A can trigger microtubule disassembly. In addition to its effect on cell cycle, asperphenin A-induced reactive oxygen species. The compound suppressed the growth of tumors in a colon cancer xenograft model without any overt toxicity and exhibited a combination effect with irinotecan, a topoisomerase I inhibitor. Moreover, we identified the aryl ketone as a key component in the molecular structure responsible for the biological activity of asperphenin A using its synthetic derivatives. Collectively, this study has revealed the antiproliferative and antitumor mechanism of asperphenin A and suggested its possibility as a chemotherapeutic agent and lead compound with a novel structure.

Anticancer Compounds Derived from Marine Diatoms

“…This has led to the discovery of new classes of chemicals with therapeutic activities. Numerous studies have reported that these metabolites exhibit different biological activities such as anticancer, antimicrobial, antiviral, and anti-inflammatory activities [8]. Marine microalgae are potential sources of biochemicals for diverse applications in biofuel industries, food, pharmaceutical, nutraceutical, and cosmetics, as shown in Figure 1.…”

Secondary Metabolites from Marine-Derived Fungi and Actinobacteria as Potential Sources of Novel Colorectal Cancer Drugs

“…The isolation of secondary metabolites from the fungus Aspergillus versicolor Ppf48 yielded several compounds, including asperphenin A (8) and asperphenin B (9) [22]. Through an SRB assay and tested upon RKO CRC cell line, compounds 8 and 9 showed strong cytotoxic activities, with IC 50 values of 0.84 and 1.26 µM, respectively.…”

Recent Advances in Chemical Biology Using Benzophenones and Diazirines as Radical Precursors

“…Their application extends beyond the common PL techniques of binding-site and biological-interactome mapping, target identification and proteome profiling, and surface conjugation techniques amongst others. They are also found in natural products that have broad-spectrum biological effects such as anticancer, antiviral, antimicrobial, and anti-inflammatory effects [2,[19][20][21][22]. The phototoxicity of this class of bioactive natural products is a probable adverse effect that may limit the widespread utilization of this pharmacophore in drug design [23].…”