Abstract：
:Effective treatments for esophageal squamous cell carcinoma (ESCC), one of the most common cancers in China, are lacking. Longikaurin A (LK-A), an ent-kauranoid diterpenoid isolated from Isodon ternifolius, has been shown to have potent cytotoxic effects on ESCC cells both in vivo and in vitro, mainly by inducing apoptosis. In this study, LK-A inhibited ESCC cells viability and induced G2/M cell cycle arrest. Moreover, LK-A was also highly effective in a KYSE-30 xenograft nude mouse model. Treatment with Z-VAD(OMe)-FMK partially attenuated LK-A-induced apoptosis. LK-A significantly induced reactive oxygen species (ROS) production in ESCC cells, and LK-A-induced apoptosis was attenuated by the ROS scavenger N-acetyl cysteine (NAC). Furthermore, we found that treatment with LK-A activated both the JNK and p38 MAPK signaling pathways, resulting in increases in ROS levels and apoptosis induction. Taken together, these findings indicate that LK-A exerts novel anti-tumor effects in ESCC cells by activating the JNK and p38 MAPK pathways and inducing increases in ROS production, which suggest that the compound may have potential as a clinical therapeutic agent.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Che Y,Wang J,Yuan Z,Li Y,Lu Z,Zhang Z,Zhang J,Wan J,Sun H,Chen Z,Pu J,He Jdoi
10.1016/j.toxlet.2017.08.005subject
Has Abstractpub_date
2017-10-05 00:00:00pages
106-115eissn
0378-4274issn
1879-3169pii
S0378-4274(17)31165-7journal_volume
280pub_type
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