Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived <i>Aspergillus</i> sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer Cells
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 <i>Aspergillus</i> sp. fungus. The compound has shown potent antiproliferative activity...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/18/2/110 |
| _version_ | 1828109424312451072 |
|---|---|
| author | Song Yi Bae Lijuan Liao So Hyun Park Won Kyung Kim Jongheon Shin Sang Kook Lee |
| author_facet | Song Yi Bae Lijuan Liao So Hyun Park Won Kyung Kim Jongheon Shin Sang Kook Lee |
| author_sort | Song Yi Bae |
| collection | DOAJ |
| description | 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 <i>Aspergillus</i> 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 G<sub>2</sub>/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. |
| first_indexed | 2024-04-11T11:02:01Z |
| format | Article |
| id | doaj.art-80e3738c53e74ce787c246a54dfa4318 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T11:02:01Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-80e3738c53e74ce787c246a54dfa43182022-12-22T04:28:30ZengMDPI AGMarine Drugs1660-33972020-02-0118211010.3390/md18020110md18020110Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived <i>Aspergillus</i> sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer CellsSong Yi Bae0Lijuan Liao1So Hyun Park2Won Kyung Kim3Jongheon Shin4Sang Kook Lee5College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaCollege of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaCollege of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaCollege of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaCollege of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaCollege of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaMarine-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 <i>Aspergillus</i> 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 G<sub>2</sub>/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.https://www.mdpi.com/1660-3397/18/2/110marine microorganism metabolite<i>aspergillus</i> sp. fungusasperpheninscolon cancerantimitotic agenttubulin polymerization |
| spellingShingle | Song Yi Bae Lijuan Liao So Hyun Park Won Kyung Kim Jongheon Shin Sang Kook Lee Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived <i>Aspergillus</i> sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer Cells Marine Drugs marine microorganism metabolite <i>aspergillus</i> sp. fungus asperphenins colon cancer antimitotic agent tubulin polymerization |
| title | Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived <i>Aspergillus</i> sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer Cells |
| title_full | Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived <i>Aspergillus</i> sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer Cells |
| title_fullStr | Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived <i>Aspergillus</i> sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer Cells |
| title_full_unstemmed | Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived <i>Aspergillus</i> sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer Cells |
| title_short | Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived <i>Aspergillus</i> sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer Cells |
| title_sort | antitumor activity of asperphenin a a lipopeptidyl benzophenone from marine derived i aspergillus i sp fungus by inhibiting tubulin polymerization in colon cancer cells |
| topic | marine microorganism metabolite <i>aspergillus</i> sp. fungus asperphenins colon cancer antimitotic agent tubulin polymerization |
| url | https://www.mdpi.com/1660-3397/18/2/110 |
| work_keys_str_mv | AT songyibae antitumoractivityofasperpheninaalipopeptidylbenzophenonefrommarinederivediaspergillusispfungusbyinhibitingtubulinpolymerizationincoloncancercells AT lijuanliao antitumoractivityofasperpheninaalipopeptidylbenzophenonefrommarinederivediaspergillusispfungusbyinhibitingtubulinpolymerizationincoloncancercells AT sohyunpark antitumoractivityofasperpheninaalipopeptidylbenzophenonefrommarinederivediaspergillusispfungusbyinhibitingtubulinpolymerizationincoloncancercells AT wonkyungkim antitumoractivityofasperpheninaalipopeptidylbenzophenonefrommarinederivediaspergillusispfungusbyinhibitingtubulinpolymerizationincoloncancercells AT jongheonshin antitumoractivityofasperpheninaalipopeptidylbenzophenonefrommarinederivediaspergillusispfungusbyinhibitingtubulinpolymerizationincoloncancercells AT sangkooklee antitumoractivityofasperpheninaalipopeptidylbenzophenonefrommarinederivediaspergillusispfungusbyinhibitingtubulinpolymerizationincoloncancercells |