FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway

Oral cancer is the most common oral malignant tumor in Taiwan. Although there exist several methods for treatment, oral cancer still has a poor prognosis and high recurrence. FLLL32, a synthetic analog of curcumin with antitumor activity, is currently known to induce melanoma apoptosis and inhibit t...

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Autores principales:	Chun-Wen Su, Chun-Yi Chuang, Yi-Tzu Chen, Wei-En Yang, Yi-Ping Pan, Chiao-Wen Lin, Shun-Fa Yang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	oral cancer FLLL32 apoptosis HO-1 p38 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/73138206ef8c41b99a8a4eaca41c9186
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spelling	oai:doaj.org-article:73138206ef8c41b99a8a4eaca41c91862021-11-11T17:17:02ZFLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway10.3390/ijms2221118601422-00671661-6596https://doaj.org/article/73138206ef8c41b99a8a4eaca41c91862021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11860https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Oral cancer is the most common oral malignant tumor in Taiwan. Although there exist several methods for treatment, oral cancer still has a poor prognosis and high recurrence. FLLL32, a synthetic analog of curcumin with antitumor activity, is currently known to induce melanoma apoptosis and inhibit tumor growth in various cancers. However, few studies have examined the mechanisms of FLLL32 in oral cancer. In this study, we explore whether FLLL32 induces apoptosis in oral cancer. We determined that FLLL32 can inhibit the cell viability of oral cancer. Next, we analyzed the effect of FLLL32 on the cell cycle of oral cancer cells and observed that the proportion of cells in the G2/M phase was increased. Additionally, annexin-V/PI double staining revealed that FLLL32 induced apoptosis in oral cancer cells. Data from the Human Apoptosis Array revealed that FLLL32 increases the expression of cleaved caspase-3 and heme oxygenase-1 (HO-1). FLLL32 activates proteins such as caspase-8, caspase-9, caspase-3, PARP, and mitogen-activated protein kinases (MAPKs) in apoptosis-related molecular mechanisms. Moreover, by using MAPK inhibitors, we suggest that FLLL32 induces the apoptosis of oral cancer cells through the p38 MAPK signaling pathway. In conclusion, our findings suggest that FLLL32 is a potential therapeutic agent for oral cancer by inducing caspase-dependent apoptosis and HO-1 activation through the p38 pathway. We believe that the activation of HO-1 and the p38 pathway by FLLL32 represent potential targets for further research in oral cancer.Chun-Wen SuChun-Yi ChuangYi-Tzu ChenWei-En YangYi-Ping PanChiao-Wen LinShun-Fa YangMDPI AGarticleoral cancerFLLL32apoptosisHO-1p38Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11860, p 11860 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oral cancer FLLL32 apoptosis HO-1 p38 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	oral cancer FLLL32 apoptosis HO-1 p38 Biology (General) QH301-705.5 Chemistry QD1-999 Chun-Wen Su Chun-Yi Chuang Yi-Tzu Chen Wei-En Yang Yi-Ping Pan Chiao-Wen Lin Shun-Fa Yang FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway
description	Oral cancer is the most common oral malignant tumor in Taiwan. Although there exist several methods for treatment, oral cancer still has a poor prognosis and high recurrence. FLLL32, a synthetic analog of curcumin with antitumor activity, is currently known to induce melanoma apoptosis and inhibit tumor growth in various cancers. However, few studies have examined the mechanisms of FLLL32 in oral cancer. In this study, we explore whether FLLL32 induces apoptosis in oral cancer. We determined that FLLL32 can inhibit the cell viability of oral cancer. Next, we analyzed the effect of FLLL32 on the cell cycle of oral cancer cells and observed that the proportion of cells in the G2/M phase was increased. Additionally, annexin-V/PI double staining revealed that FLLL32 induced apoptosis in oral cancer cells. Data from the Human Apoptosis Array revealed that FLLL32 increases the expression of cleaved caspase-3 and heme oxygenase-1 (HO-1). FLLL32 activates proteins such as caspase-8, caspase-9, caspase-3, PARP, and mitogen-activated protein kinases (MAPKs) in apoptosis-related molecular mechanisms. Moreover, by using MAPK inhibitors, we suggest that FLLL32 induces the apoptosis of oral cancer cells through the p38 MAPK signaling pathway. In conclusion, our findings suggest that FLLL32 is a potential therapeutic agent for oral cancer by inducing caspase-dependent apoptosis and HO-1 activation through the p38 pathway. We believe that the activation of HO-1 and the p38 pathway by FLLL32 represent potential targets for further research in oral cancer.
format	article
author	Chun-Wen Su Chun-Yi Chuang Yi-Tzu Chen Wei-En Yang Yi-Ping Pan Chiao-Wen Lin Shun-Fa Yang
author_facet	Chun-Wen Su Chun-Yi Chuang Yi-Tzu Chen Wei-En Yang Yi-Ping Pan Chiao-Wen Lin Shun-Fa Yang
author_sort	Chun-Wen Su
title	FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway
title_short	FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway
title_full	FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway
title_fullStr	FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway
title_full_unstemmed	FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway
title_sort	flll32 triggers caspase-mediated apoptotic cell death in human oral cancer cells by regulating the p38 pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/73138206ef8c41b99a8a4eaca41c9186
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FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway

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