Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells
Oral squamous cell carcinoma (OSCC) accounts for about 90% of all head and neck cancers, the prognosis is very poor, and there are no effective targeted therapies. Herein, we isolated Machilin D (Mach), a lignin, from the roots of <i>Saururus chinensis</i> (<i>S. chinensis</i>...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/5/4576 |
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| author | Hyung-Mun Yun Yoon-Ju Kwon Eonmi Kim Hea-Jong Chung Kyung-Ran Park |
| author_facet | Hyung-Mun Yun Yoon-Ju Kwon Eonmi Kim Hea-Jong Chung Kyung-Ran Park |
| author_sort | Hyung-Mun Yun |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) accounts for about 90% of all head and neck cancers, the prognosis is very poor, and there are no effective targeted therapies. Herein, we isolated Machilin D (Mach), a lignin, from the roots of <i>Saururus chinensis</i> (<i>S. chinensis</i>) and assessed its inhibitory effects on OSCC. Herein, Mach had significant cytotoxicity against human OSCC cells and showed inhibitory effects against cell adhesion, migration, and invasion by inhibiting adhesion molecules, including the FAK/Src pathway. Mach suppressed the PI3K/AKT/mTOR/p70S6K pathway and MAPKs, leading to apoptotic cell death. We investigated other modes of programmed cell death in these cells and found that Mach increased LC3I/II and Beclin1 and decreased p62, leading to autophagosomes, and suppressed the necroptosis-regulatory proteins RIP1 and MLKL. Our findings provide evidence that the inhibitory effects of Mach against human YD-10B OSCC cells are related to the promotion of apoptosis and autophagy and inhibition of necroptosis and are mediated via focal adhesion molecules. |
| first_indexed | 2024-03-11T07:22:31Z |
| format | Article |
| id | doaj.art-55d85964a6834a6297fba7295064725d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T07:22:31Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-55d85964a6834a6297fba7295064725d2023-11-17T07:50:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245457610.3390/ijms24054576Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma CellsHyung-Mun Yun0Yoon-Ju Kwon1Eonmi Kim2Hea-Jong Chung3Kyung-Ran Park4Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of KoreaNational Development Institute for Korean Medicine, Gyeongsan 38540, Republic of KoreaNational Development Institute for Korean Medicine, Gyeongsan 38540, Republic of KoreaGwangju Center, Korea Basic Science Institute (KBSI), Gwangju 61751, Republic of KoreaGwangju Center, Korea Basic Science Institute (KBSI), Gwangju 61751, Republic of KoreaOral squamous cell carcinoma (OSCC) accounts for about 90% of all head and neck cancers, the prognosis is very poor, and there are no effective targeted therapies. Herein, we isolated Machilin D (Mach), a lignin, from the roots of <i>Saururus chinensis</i> (<i>S. chinensis</i>) and assessed its inhibitory effects on OSCC. Herein, Mach had significant cytotoxicity against human OSCC cells and showed inhibitory effects against cell adhesion, migration, and invasion by inhibiting adhesion molecules, including the FAK/Src pathway. Mach suppressed the PI3K/AKT/mTOR/p70S6K pathway and MAPKs, leading to apoptotic cell death. We investigated other modes of programmed cell death in these cells and found that Mach increased LC3I/II and Beclin1 and decreased p62, leading to autophagosomes, and suppressed the necroptosis-regulatory proteins RIP1 and MLKL. Our findings provide evidence that the inhibitory effects of Mach against human YD-10B OSCC cells are related to the promotion of apoptosis and autophagy and inhibition of necroptosis and are mediated via focal adhesion molecules.https://www.mdpi.com/1422-0067/24/5/4576apoptosisautophagyMachilin DnecroptosisOSCC |
| spellingShingle | Hyung-Mun Yun Yoon-Ju Kwon Eonmi Kim Hea-Jong Chung Kyung-Ran Park Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells International Journal of Molecular Sciences apoptosis autophagy Machilin D necroptosis OSCC |
| title | Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells |
| title_full | Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells |
| title_fullStr | Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells |
| title_full_unstemmed | Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells |
| title_short | Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells |
| title_sort | machilin d promotes apoptosis and autophagy and inhibits necroptosis in human oral squamous cell carcinoma cells |
| topic | apoptosis autophagy Machilin D necroptosis OSCC |
| url | https://www.mdpi.com/1422-0067/24/5/4576 |
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