Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling
Oral squamous cell carcinoma (OSCC) is the sixth most common type of cancer worldwide. Despite advancement in treatment, advanced-stage OSCC is associated with poor prognosis and high mortality. The present study aimed to investigate the anticancer activities of semilicoisoflavone B (SFB), which is...
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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/1422-0067/24/5/4505 |
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| author | Ming-Ju Hsieh Hsin-Yu Ho Yu-Sheng Lo Chia-Chieh Lin Yi-Ching Chuang Mosleh Mohammad Abomughaid Ming-Chang Hsieh Mu-Kuan Chen |
| author_facet | Ming-Ju Hsieh Hsin-Yu Ho Yu-Sheng Lo Chia-Chieh Lin Yi-Ching Chuang Mosleh Mohammad Abomughaid Ming-Chang Hsieh Mu-Kuan Chen |
| author_sort | Ming-Ju Hsieh |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) is the sixth most common type of cancer worldwide. Despite advancement in treatment, advanced-stage OSCC is associated with poor prognosis and high mortality. The present study aimed to investigate the anticancer activities of semilicoisoflavone B (SFB), which is a natural phenolic compound isolated from <i>Glycyrrhiza species</i>. The results revealed that SFB reduces OSCC cell viability by targeting cell cycle and apoptosis. The compound caused cell cycle arrest at the G2/M phase and downregulated the expressions of cell cycle regulators including cyclin A and cyclin-dependent kinase (CDK) 2, 6, and 4. Moreover, SFB induced apoptosis by activating poly-ADP-ribose polymerase (PARP) and caspases 3, 8, and 9. It increased the expressions of pro-apoptotic proteins Bax and Bak, reduced the expressions of anti-apoptotic proteins Bcl-2 and Bcl-xL, and increased the expressions of the death receptor pathway protein Fas cell surface death receptor (FAS), Fas-associated death domain protein (FADD), and TNFR1-associated death domain protein (TRADD). SFB was found to mediate oral cancer cell apoptosis by increasing reactive oxygen species (ROS) production. The treatment of the cells with N-acetyl cysteine (NAC) caused a reduction in pro-apoptotic potential of SFB. Regarding upstream signaling, SFB reduced the phosphorylation of AKT, ERK1/2, p38, and JNK1/2 and suppressed the activation of Ras, Raf, and MEK. The human apoptosis array conducted in the study identified that SFB downregulated survivin expression to induce oral cancer cell apoptosis. Taken together, the study identifies SFB as a potent anticancer agent that might be used clinically to manage human OSCC. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T07:23:04Z |
| publishDate | 2023-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e2a4aec146c84c38ad57bdfc5ae88abb2023-11-17T07:49:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245450510.3390/ijms24054505Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK SignalingMing-Ju Hsieh0Hsin-Yu Ho1Yu-Sheng Lo2Chia-Chieh Lin3Yi-Ching Chuang4Mosleh Mohammad Abomughaid5Ming-Chang Hsieh6Mu-Kuan Chen7Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, TaiwanOral Cancer Research Center, Changhua Christian Hospital, Changhua 500, TaiwanOral Cancer Research Center, Changhua Christian Hospital, Changhua 500, TaiwanOral Cancer Research Center, Changhua Christian Hospital, Changhua 500, TaiwanOral Cancer Research Center, Changhua Christian Hospital, Changhua 500, TaiwanDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi ArabiaSchool of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, TaiwanOral squamous cell carcinoma (OSCC) is the sixth most common type of cancer worldwide. Despite advancement in treatment, advanced-stage OSCC is associated with poor prognosis and high mortality. The present study aimed to investigate the anticancer activities of semilicoisoflavone B (SFB), which is a natural phenolic compound isolated from <i>Glycyrrhiza species</i>. The results revealed that SFB reduces OSCC cell viability by targeting cell cycle and apoptosis. The compound caused cell cycle arrest at the G2/M phase and downregulated the expressions of cell cycle regulators including cyclin A and cyclin-dependent kinase (CDK) 2, 6, and 4. Moreover, SFB induced apoptosis by activating poly-ADP-ribose polymerase (PARP) and caspases 3, 8, and 9. It increased the expressions of pro-apoptotic proteins Bax and Bak, reduced the expressions of anti-apoptotic proteins Bcl-2 and Bcl-xL, and increased the expressions of the death receptor pathway protein Fas cell surface death receptor (FAS), Fas-associated death domain protein (FADD), and TNFR1-associated death domain protein (TRADD). SFB was found to mediate oral cancer cell apoptosis by increasing reactive oxygen species (ROS) production. The treatment of the cells with N-acetyl cysteine (NAC) caused a reduction in pro-apoptotic potential of SFB. Regarding upstream signaling, SFB reduced the phosphorylation of AKT, ERK1/2, p38, and JNK1/2 and suppressed the activation of Ras, Raf, and MEK. The human apoptosis array conducted in the study identified that SFB downregulated survivin expression to induce oral cancer cell apoptosis. Taken together, the study identifies SFB as a potent anticancer agent that might be used clinically to manage human OSCC.https://www.mdpi.com/1422-0067/24/5/4505oral squamous cell carcinomasemilicoisoflavone BMAPKRas/Raf/MEKROSsurvivin |
| spellingShingle | Ming-Ju Hsieh Hsin-Yu Ho Yu-Sheng Lo Chia-Chieh Lin Yi-Ching Chuang Mosleh Mohammad Abomughaid Ming-Chang Hsieh Mu-Kuan Chen Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling International Journal of Molecular Sciences oral squamous cell carcinoma semilicoisoflavone B MAPK Ras/Raf/MEK ROS survivin |
| title | Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling |
| title_full | Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling |
| title_fullStr | Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling |
| title_full_unstemmed | Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling |
| title_short | Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling |
| title_sort | semilicoisoflavone b induces apoptosis of oral cancer cells by inducing ros production and downregulating mapk and ras raf mek signaling |
| topic | oral squamous cell carcinoma semilicoisoflavone B MAPK Ras/Raf/MEK ROS survivin |
| url | https://www.mdpi.com/1422-0067/24/5/4505 |
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