Inhibitory Effects of the Polyphenols from the Root of <i>Rhizophora apiculata</i> Blume on Fatty Acid Synthase Activity and Human Colon Cancer Cells
Marine mangrove vegetation has been traditionally employed in folk medicine to address various ailments. Notably, <i>Rhizophora apiculata</i> Blume has exhibited noteworthy properties, demonstrating efficacy against cancer, viruses, and bacteria. The enzyme fatty acid synthase (FAS) play...
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MDPI AG
2024-03-01
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| Online Access: | https://www.mdpi.com/1420-3049/29/5/1180 |
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| author | Yan Liang Yue Ban Lei Liu Yanchun Li |
| author_facet | Yan Liang Yue Ban Lei Liu Yanchun Li |
| author_sort | Yan Liang |
| collection | DOAJ |
| description | Marine mangrove vegetation has been traditionally employed in folk medicine to address various ailments. Notably, <i>Rhizophora apiculata</i> Blume has exhibited noteworthy properties, demonstrating efficacy against cancer, viruses, and bacteria. The enzyme fatty acid synthase (FAS) plays a pivotal role in de novo fatty acid synthesis, making it a promising target for combating colon cancer. Our study focused on evaluating the FAS inhibitory effects of both the crude extract and three isolated compounds from <i>R. apiculata</i>. The n-butanol fraction of <i>R. apiculata</i> extract (BFR) demonstrated a significant inhibition of FAS, with an IC<sub>50</sub> value of 93.0 µg/mL. For inhibition via lyoniresinol-3α-<i>O</i>-β-rhamnopyranoside (LR), the corresponding IC<sub>50</sub> value was 20.1 µg/mL (35.5 µM). LR competitively inhibited the FAS reaction with acetyl-CoA, noncompetitively with malonyl-CoA, and in a mixed manner with NADPH. Our results also suggest that both BFR and LR reversibly bind to the KR domain of FAS, hindering the reduction of saturated acyl groups in fatty acid synthesis. Furthermore, BFR and LR displayed time-dependent inhibition for FAS, with k<sub>obs</sub> values of 0.0045 min<sup>−1</sup> and 0.026 min<sup>−1</sup>, respectively. LR also exhibited time-dependent inhibition on the KR domain, with a k<sub>obs</sub> value of 0.019 min<sup>−1</sup>. In human colon cancer cells, LR demonstrated the ability to reduce viability and inhibit intracellular FAS activity. Notably, the effects of LR on human colon cancer cells could be reversed with the end product of FAS-catalyzed chemical reactions, affirming the specificity of LR on FAS. These findings underscore the potential of BFR and LR as potent FAS inhibitors, presenting novel avenues for the treatment of human colon cancer. |
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| spelling | doaj.art-620eedf7109f40cc90a0a1d6f32196822024-03-12T16:51:24ZengMDPI AGMolecules1420-30492024-03-01295118010.3390/molecules29051180Inhibitory Effects of the Polyphenols from the Root of <i>Rhizophora apiculata</i> Blume on Fatty Acid Synthase Activity and Human Colon Cancer CellsYan Liang0Yue Ban1Lei Liu2Yanchun Li3School of Sports Sciences, Beijing Sport University, No. 48, Xinxi Road, Beijing 100084, ChinaSchool of Kinesiology and Health, Capital University of Physical Education and Sports, No. 11, Beisanhuanxi Road, Beijing 100191, ChinaCollege of Chemistry and Materials Engineering, Beijing Technology & Business University (BTBU), Beijing 100048, ChinaSchool of Sports Sciences, Beijing Sport University, No. 48, Xinxi Road, Beijing 100084, ChinaMarine mangrove vegetation has been traditionally employed in folk medicine to address various ailments. Notably, <i>Rhizophora apiculata</i> Blume has exhibited noteworthy properties, demonstrating efficacy against cancer, viruses, and bacteria. The enzyme fatty acid synthase (FAS) plays a pivotal role in de novo fatty acid synthesis, making it a promising target for combating colon cancer. Our study focused on evaluating the FAS inhibitory effects of both the crude extract and three isolated compounds from <i>R. apiculata</i>. The n-butanol fraction of <i>R. apiculata</i> extract (BFR) demonstrated a significant inhibition of FAS, with an IC<sub>50</sub> value of 93.0 µg/mL. For inhibition via lyoniresinol-3α-<i>O</i>-β-rhamnopyranoside (LR), the corresponding IC<sub>50</sub> value was 20.1 µg/mL (35.5 µM). LR competitively inhibited the FAS reaction with acetyl-CoA, noncompetitively with malonyl-CoA, and in a mixed manner with NADPH. Our results also suggest that both BFR and LR reversibly bind to the KR domain of FAS, hindering the reduction of saturated acyl groups in fatty acid synthesis. Furthermore, BFR and LR displayed time-dependent inhibition for FAS, with k<sub>obs</sub> values of 0.0045 min<sup>−1</sup> and 0.026 min<sup>−1</sup>, respectively. LR also exhibited time-dependent inhibition on the KR domain, with a k<sub>obs</sub> value of 0.019 min<sup>−1</sup>. In human colon cancer cells, LR demonstrated the ability to reduce viability and inhibit intracellular FAS activity. Notably, the effects of LR on human colon cancer cells could be reversed with the end product of FAS-catalyzed chemical reactions, affirming the specificity of LR on FAS. These findings underscore the potential of BFR and LR as potent FAS inhibitors, presenting novel avenues for the treatment of human colon cancer.https://www.mdpi.com/1420-3049/29/5/1180fatty acid synthaseinhibitorhuman colon cancerβ-ketoacyl reductase<i>Rhizophora apiculata</i> Blumepolyphenol |
| spellingShingle | Yan Liang Yue Ban Lei Liu Yanchun Li Inhibitory Effects of the Polyphenols from the Root of <i>Rhizophora apiculata</i> Blume on Fatty Acid Synthase Activity and Human Colon Cancer Cells Molecules fatty acid synthase inhibitor human colon cancer β-ketoacyl reductase <i>Rhizophora apiculata</i> Blume polyphenol |
| title | Inhibitory Effects of the Polyphenols from the Root of <i>Rhizophora apiculata</i> Blume on Fatty Acid Synthase Activity and Human Colon Cancer Cells |
| title_full | Inhibitory Effects of the Polyphenols from the Root of <i>Rhizophora apiculata</i> Blume on Fatty Acid Synthase Activity and Human Colon Cancer Cells |
| title_fullStr | Inhibitory Effects of the Polyphenols from the Root of <i>Rhizophora apiculata</i> Blume on Fatty Acid Synthase Activity and Human Colon Cancer Cells |
| title_full_unstemmed | Inhibitory Effects of the Polyphenols from the Root of <i>Rhizophora apiculata</i> Blume on Fatty Acid Synthase Activity and Human Colon Cancer Cells |
| title_short | Inhibitory Effects of the Polyphenols from the Root of <i>Rhizophora apiculata</i> Blume on Fatty Acid Synthase Activity and Human Colon Cancer Cells |
| title_sort | inhibitory effects of the polyphenols from the root of i rhizophora apiculata i blume on fatty acid synthase activity and human colon cancer cells |
| topic | fatty acid synthase inhibitor human colon cancer β-ketoacyl reductase <i>Rhizophora apiculata</i> Blume polyphenol |
| url | https://www.mdpi.com/1420-3049/29/5/1180 |
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