Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives.
Dihydroartemisinin (DHA) and artesunate (ARS), two artemisinin derivatives, have efficacious anticancer activities against human hepatocarcinoma (HCC) cells. This study aims to study the anticancer action of the combination treatment of DHA/ARS and farnesylthiosalicylic acid (FTS), a Ras inhibitor,...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5300221?pdf=render |
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| author | Liping Wu Yilin Pang Guiqi Qin Gaina Xi Shengnan Wu Xiaoping Wang Tongsheng Chen |
| author_facet | Liping Wu Yilin Pang Guiqi Qin Gaina Xi Shengnan Wu Xiaoping Wang Tongsheng Chen |
| author_sort | Liping Wu |
| collection | DOAJ |
| description | Dihydroartemisinin (DHA) and artesunate (ARS), two artemisinin derivatives, have efficacious anticancer activities against human hepatocarcinoma (HCC) cells. This study aims to study the anticancer action of the combination treatment of DHA/ARS and farnesylthiosalicylic acid (FTS), a Ras inhibitor, in HCC cells (Huh-7 and HepG2 cell lines). FTS pretreatment significantly enhanced DHA/ARS-induced phosphatidylserine (PS) externalization, Bak/Bax activation, mitochondrial membrane depolarization, cytochrome c release, and caspase-8 and -9 activations, characteristics of the extrinsic and intrinsic apoptosis. Pretreatment with Z-IETD-FMK (caspase-8 inhibitor) potently prevented the cytotoxicity of the combination treatment of DHA/ARS and FTS, and pretreatment with Z-VAD-FMK (pan-caspase inhibitor) significantly inhibited the loss of ΔΨm induced by DHA/ARS treatment or the combination treatment of DHA/ARS and FTS in HCC cells. Furthermore, silencing Bak/Bax modestly but significantly inhibited the cytotoxicity of the combination treatment of DHA/ARS and FTS. Interestingly, pretreatment with an antioxidant N-Acetyle-Cysteine (NAC) significantly prevented the cytotoxicity of the combination treatment of DHA and FTS instead of the combination treatment of ARS and FTS, suggesting that reactive oxygen species (ROS) played a key role in the anticancer action of the combination treatment of DHA and FTS. Similar to FTS, DHA/ARS also significantly prevented Ras activation. Collectively, our data demonstrate that FTS potently sensitizes Huh-7 and HepG2 cells to artemisinin derivatives via accelerating the extrinsic and intrinsic apoptotic pathways. |
| first_indexed | 2024-12-21T17:00:23Z |
| format | Article |
| id | doaj.art-533fa43c326641769db15665be42481f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T17:00:23Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-533fa43c326641769db15665be42481f2022-12-21T18:56:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017184010.1371/journal.pone.0171840Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives.Liping WuYilin PangGuiqi QinGaina XiShengnan WuXiaoping WangTongsheng ChenDihydroartemisinin (DHA) and artesunate (ARS), two artemisinin derivatives, have efficacious anticancer activities against human hepatocarcinoma (HCC) cells. This study aims to study the anticancer action of the combination treatment of DHA/ARS and farnesylthiosalicylic acid (FTS), a Ras inhibitor, in HCC cells (Huh-7 and HepG2 cell lines). FTS pretreatment significantly enhanced DHA/ARS-induced phosphatidylserine (PS) externalization, Bak/Bax activation, mitochondrial membrane depolarization, cytochrome c release, and caspase-8 and -9 activations, characteristics of the extrinsic and intrinsic apoptosis. Pretreatment with Z-IETD-FMK (caspase-8 inhibitor) potently prevented the cytotoxicity of the combination treatment of DHA/ARS and FTS, and pretreatment with Z-VAD-FMK (pan-caspase inhibitor) significantly inhibited the loss of ΔΨm induced by DHA/ARS treatment or the combination treatment of DHA/ARS and FTS in HCC cells. Furthermore, silencing Bak/Bax modestly but significantly inhibited the cytotoxicity of the combination treatment of DHA/ARS and FTS. Interestingly, pretreatment with an antioxidant N-Acetyle-Cysteine (NAC) significantly prevented the cytotoxicity of the combination treatment of DHA and FTS instead of the combination treatment of ARS and FTS, suggesting that reactive oxygen species (ROS) played a key role in the anticancer action of the combination treatment of DHA and FTS. Similar to FTS, DHA/ARS also significantly prevented Ras activation. Collectively, our data demonstrate that FTS potently sensitizes Huh-7 and HepG2 cells to artemisinin derivatives via accelerating the extrinsic and intrinsic apoptotic pathways.http://europepmc.org/articles/PMC5300221?pdf=render |
| spellingShingle | Liping Wu Yilin Pang Guiqi Qin Gaina Xi Shengnan Wu Xiaoping Wang Tongsheng Chen Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives. PLoS ONE |
| title | Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives. |
| title_full | Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives. |
| title_fullStr | Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives. |
| title_full_unstemmed | Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives. |
| title_short | Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives. |
| title_sort | farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives |
| url | http://europepmc.org/articles/PMC5300221?pdf=render |
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