Latifolin, a Natural Flavonoid, Isolated from the Heartwood of <i>Dalbergia odorifera</i> Induces Bioactivities through Apoptosis, Autophagy, and Necroptosis in Human Oral Squamous Cell Carcinoma
Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm with frequent metastasis and high mortality in the oral cavity. Plant-derived natural compounds are actively progressing as a trend for cancer treatment. Latifolin (Latif), is a natural flavonoid isolated from the heartwood of...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/13629 |
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| author | Hyung-Mun Yun Ji Eun Park Joon Yeop Lee Kyung-Ran Park |
| author_facet | Hyung-Mun Yun Ji Eun Park Joon Yeop Lee Kyung-Ran Park |
| author_sort | Hyung-Mun Yun |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm with frequent metastasis and high mortality in the oral cavity. Plant-derived natural compounds are actively progressing as a trend for cancer treatment. Latifolin (Latif), is a natural flavonoid isolated from the heartwood of <i>Dalbergia odorifera</i> T. Chen (<i>D. odorifera</i>) has been known to have beneficial effects on anti-aging, anti-carcinogenic, anti-inflammatory, and cardio-protective activities. However, the anti-cancer effects of Latif are unknown in OSCC. Herein, as a result of analysis in terms of the aggressive features of OSCCs, we found that Latif significantly inhibited the cell proliferation of human YD-8 and YD-10B OSCCs, and caused the anti-metastatic activities by effectively blocking cell migration, invasion, and adhesion via the inactivation of focal adhesion kinase (FAK)/non-receptor tyrosine kinase (Src). Moreover, we found that Latif induced apoptotic cell death to suppress the cell survival and proliferation of YD-10B OSCCs by targeting PI3K/AKT/mTOR/p70S6K signaling. Finally, we analyzed in terms of autophagy and necroptosis, which are other mechanisms of programmed cell death and survival compared to apoptosis in YD-10B OSCCs. We found that Latif suppressed autophagic-related proteins and autophagosome formation, and also Latif inhibited necroptosis by dephosphorylating necroptosis-regulatory proteins (RIP1, RIP3, and MLKL). Given these findings, our results provided new evidence for Latif’s biological effect and mechanism in YD-10B OSCCs, suggesting that Latif may be a new candidate for patients with OSCCs. |
| first_indexed | 2024-03-09T18:59:29Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:59:29Z |
| publishDate | 2022-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-45ab2e39ec96440ca95e9c85fc1ba0c62023-11-24T05:11:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123211362910.3390/ijms232113629Latifolin, a Natural Flavonoid, Isolated from the Heartwood of <i>Dalbergia odorifera</i> Induces Bioactivities through Apoptosis, Autophagy, and Necroptosis in Human Oral Squamous Cell CarcinomaHyung-Mun Yun0Ji Eun Park1Joon Yeop Lee2Kyung-Ran Park3Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, KoreaNational Development Institute for Korean Medicine, Gyeongsan 38540, KoreaNational Development Institute for Korean Medicine, Gyeongsan 38540, KoreaGwangju Center, Korea Basic Science Institute (KBSI), Gwangju 61751, KoreaOral squamous cell carcinoma (OSCC) is the most common malignant neoplasm with frequent metastasis and high mortality in the oral cavity. Plant-derived natural compounds are actively progressing as a trend for cancer treatment. Latifolin (Latif), is a natural flavonoid isolated from the heartwood of <i>Dalbergia odorifera</i> T. Chen (<i>D. odorifera</i>) has been known to have beneficial effects on anti-aging, anti-carcinogenic, anti-inflammatory, and cardio-protective activities. However, the anti-cancer effects of Latif are unknown in OSCC. Herein, as a result of analysis in terms of the aggressive features of OSCCs, we found that Latif significantly inhibited the cell proliferation of human YD-8 and YD-10B OSCCs, and caused the anti-metastatic activities by effectively blocking cell migration, invasion, and adhesion via the inactivation of focal adhesion kinase (FAK)/non-receptor tyrosine kinase (Src). Moreover, we found that Latif induced apoptotic cell death to suppress the cell survival and proliferation of YD-10B OSCCs by targeting PI3K/AKT/mTOR/p70S6K signaling. Finally, we analyzed in terms of autophagy and necroptosis, which are other mechanisms of programmed cell death and survival compared to apoptosis in YD-10B OSCCs. We found that Latif suppressed autophagic-related proteins and autophagosome formation, and also Latif inhibited necroptosis by dephosphorylating necroptosis-regulatory proteins (RIP1, RIP3, and MLKL). Given these findings, our results provided new evidence for Latif’s biological effect and mechanism in YD-10B OSCCs, suggesting that Latif may be a new candidate for patients with OSCCs.https://www.mdpi.com/1422-0067/23/21/13629apoptosisautophagy<i>D. odorifera</i>LatifnecroptosisOSCCs |
| spellingShingle | Hyung-Mun Yun Ji Eun Park Joon Yeop Lee Kyung-Ran Park Latifolin, a Natural Flavonoid, Isolated from the Heartwood of <i>Dalbergia odorifera</i> Induces Bioactivities through Apoptosis, Autophagy, and Necroptosis in Human Oral Squamous Cell Carcinoma International Journal of Molecular Sciences apoptosis autophagy <i>D. odorifera</i> Latif necroptosis OSCCs |
| title | Latifolin, a Natural Flavonoid, Isolated from the Heartwood of <i>Dalbergia odorifera</i> Induces Bioactivities through Apoptosis, Autophagy, and Necroptosis in Human Oral Squamous Cell Carcinoma |
| title_full | Latifolin, a Natural Flavonoid, Isolated from the Heartwood of <i>Dalbergia odorifera</i> Induces Bioactivities through Apoptosis, Autophagy, and Necroptosis in Human Oral Squamous Cell Carcinoma |
| title_fullStr | Latifolin, a Natural Flavonoid, Isolated from the Heartwood of <i>Dalbergia odorifera</i> Induces Bioactivities through Apoptosis, Autophagy, and Necroptosis in Human Oral Squamous Cell Carcinoma |
| title_full_unstemmed | Latifolin, a Natural Flavonoid, Isolated from the Heartwood of <i>Dalbergia odorifera</i> Induces Bioactivities through Apoptosis, Autophagy, and Necroptosis in Human Oral Squamous Cell Carcinoma |
| title_short | Latifolin, a Natural Flavonoid, Isolated from the Heartwood of <i>Dalbergia odorifera</i> Induces Bioactivities through Apoptosis, Autophagy, and Necroptosis in Human Oral Squamous Cell Carcinoma |
| title_sort | latifolin a natural flavonoid isolated from the heartwood of i dalbergia odorifera i induces bioactivities through apoptosis autophagy and necroptosis in human oral squamous cell carcinoma |
| topic | apoptosis autophagy <i>D. odorifera</i> Latif necroptosis OSCCs |
| url | https://www.mdpi.com/1422-0067/23/21/13629 |
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