Trichostatin A activates FOXO1 and induces autophagy in osteosarcoma
Introduction Histone deacetylase inhibitors (HDACIs) inhibit human osteosarcoma growth and cause apoptosis. Previously, we reported that HDACIs induce autophagy via the FOXO1 pathway. Whether there is involvement of autophagy in anti-osteosarcoma activity of HDACIs is still unknown. Material and me...
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2018
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oai:doaj.org-article:39944e1f64e040dcb4ca6d94c51782f52021-12-02T16:58:24ZTrichostatin A activates FOXO1 and induces autophagy in osteosarcoma1734-19221896-915110.5114/aoms.2018.73860https://doaj.org/article/39944e1f64e040dcb4ca6d94c51782f52018-12-01T00:00:00Zhttps://www.archivesofmedicalscience.com/Trichostatin-A-activates-FOXO1-and-induces-autophagy-in-osteosarcoma,81571,0,2.htmlhttps://doaj.org/toc/1734-1922https://doaj.org/toc/1896-9151Introduction Histone deacetylase inhibitors (HDACIs) inhibit human osteosarcoma growth and cause apoptosis. Previously, we reported that HDACIs induce autophagy via the FOXO1 pathway. Whether there is involvement of autophagy in anti-osteosarcoma activity of HDACIs is still unknown. Material and methods Confocal microscopy was performed to determine the formation of GFP-LC3 puncta. Western blotting was conducted to measure FOXO1, and autophagy-related protein levels. Small interference RNA (siRNA) specific for FOXO1 was transfected into U2OS cells to knock down FOXO1 expression level. Flow cytometry was performed to quantify cell death. Results In this study, we first observed that trichostatin A (TSA) induces autophagy in human osteosarcoma cells. Moreover, we found that TSA treatment inhibits the mammalian target of rapamycin (mTOR) signaling pathway and enhances forkhead box O1 (FOXO1) transcriptional activity, which is responsible for the increased autophagy level, while suppression of FOXO1 function by siRNA knockdown markedly decreases TSA-induced autophagy. Conclusions We found that inhibition of autophagy, either by autophagy inhibitors or ATG gene knockdown, markedly enhances TSA-caused cell death. Taken together, our studies reveal the function of autophagy in HDACI-caused osteosarcoma cell death and thus support the development of a novel therapeutic strategy by combining HDACIs and autophagy inhibitors in osteosarcoma treatment.Yunjuan BaiYun ChenXiaochen ChenJiukun JiangXiao WangLiping WangJigang WangJianbin ZhangLiang GaoTermedia Publishing Housearticleosteosarcomaautophagyfoxo1tsatrichostatin aautophagyforkhead box o1mammalian target of rapamycinMedicineRENArchives of Medical Science, Vol 15, Iss 1, Pp 204-213 (2018) |
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DOAJ |
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osteosarcoma autophagy foxo1 tsa trichostatin a autophagy forkhead box o1 mammalian target of rapamycin Medicine R |
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osteosarcoma autophagy foxo1 tsa trichostatin a autophagy forkhead box o1 mammalian target of rapamycin Medicine R Yunjuan Bai Yun Chen Xiaochen Chen Jiukun Jiang Xiao Wang Liping Wang Jigang Wang Jianbin Zhang Liang Gao Trichostatin A activates FOXO1 and induces autophagy in osteosarcoma |
| description |
Introduction
Histone deacetylase inhibitors (HDACIs) inhibit human osteosarcoma growth and cause apoptosis. Previously, we reported that HDACIs induce autophagy via the FOXO1 pathway. Whether there is involvement of autophagy in anti-osteosarcoma activity of HDACIs is still unknown.
Material and methods
Confocal microscopy was performed to determine the formation of GFP-LC3 puncta. Western blotting was conducted to measure FOXO1, and autophagy-related protein levels. Small interference RNA (siRNA) specific for FOXO1 was transfected into U2OS cells to knock down FOXO1 expression level. Flow cytometry was performed to quantify cell death.
Results
In this study, we first observed that trichostatin A (TSA) induces autophagy in human osteosarcoma cells. Moreover, we found that TSA treatment inhibits the mammalian target of rapamycin (mTOR) signaling pathway and enhances forkhead box O1 (FOXO1) transcriptional activity, which is responsible for the increased autophagy level, while suppression of FOXO1 function by siRNA knockdown markedly decreases TSA-induced autophagy.
Conclusions
We found that inhibition of autophagy, either by autophagy inhibitors or ATG gene knockdown, markedly enhances TSA-caused cell death. Taken together, our studies reveal the function of autophagy in HDACI-caused osteosarcoma cell death and thus support the development of a novel therapeutic strategy by combining HDACIs and autophagy inhibitors in osteosarcoma treatment. |
| format |
article |
| author |
Yunjuan Bai Yun Chen Xiaochen Chen Jiukun Jiang Xiao Wang Liping Wang Jigang Wang Jianbin Zhang Liang Gao |
| author_facet |
Yunjuan Bai Yun Chen Xiaochen Chen Jiukun Jiang Xiao Wang Liping Wang Jigang Wang Jianbin Zhang Liang Gao |
| author_sort |
Yunjuan Bai |
| title |
Trichostatin A activates FOXO1 and induces autophagy in osteosarcoma |
| title_short |
Trichostatin A activates FOXO1 and induces autophagy in osteosarcoma |
| title_full |
Trichostatin A activates FOXO1 and induces autophagy in osteosarcoma |
| title_fullStr |
Trichostatin A activates FOXO1 and induces autophagy in osteosarcoma |
| title_full_unstemmed |
Trichostatin A activates FOXO1 and induces autophagy in osteosarcoma |
| title_sort |
trichostatin a activates foxo1 and induces autophagy in osteosarcoma |
| publisher |
Termedia Publishing House |
| publishDate |
2018 |
| url |
https://doaj.org/article/39944e1f64e040dcb4ca6d94c51782f5 |
| work_keys_str_mv |
AT yunjuanbai trichostatinaactivatesfoxo1andinducesautophagyinosteosarcoma AT yunchen trichostatinaactivatesfoxo1andinducesautophagyinosteosarcoma AT xiaochenchen trichostatinaactivatesfoxo1andinducesautophagyinosteosarcoma AT jiukunjiang trichostatinaactivatesfoxo1andinducesautophagyinosteosarcoma AT xiaowang trichostatinaactivatesfoxo1andinducesautophagyinosteosarcoma AT lipingwang trichostatinaactivatesfoxo1andinducesautophagyinosteosarcoma AT jigangwang trichostatinaactivatesfoxo1andinducesautophagyinosteosarcoma AT jianbinzhang trichostatinaactivatesfoxo1andinducesautophagyinosteosarcoma AT lianggao trichostatinaactivatesfoxo1andinducesautophagyinosteosarcoma |
| _version_ |
1718382320105291776 |