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Lapachol is a novel ribosomal protein S6 kinase 2 inhibitor that suppresses growth and induces intrinsic apoptosis in esophageal squamous cell carcinoma cells
Author(s) -
Zu Xueyin,
Xie Xiaomeng,
Zhang Yuanyuan,
Liu Kangdong,
Bode Ann M.,
Dong Zigang,
Kim Dong Joon
Publication year - 2019
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6415
Subject(s) - apoptosis , ribosomal protein s6 , cell growth , growth inhibition , cytochrome c , ribosomal s6 kinase , chemistry , protein kinase a , microbiology and biotechnology , kinase , squamous carcinoma , biology , biochemistry , protein kinase b , carcinoma , protein phosphorylation , p70 s6 kinase 1 , genetics
Lapachol is a 1,4‐naphthoquinone that is isolated from the Bignoniaceae family. It has been reported to exert anti‐inflammatory, antibacterial, and anticancer activities. However, the anticancer activity of lapachol and its molecular mechanisms against esophageal squamous cell carcinoma (ESCC) cells have not been fully investigated. Herein, we report that lapachol is a novel ribosomal protein S6 kinase 2 (RSK2) inhibitor that suppresses growth and induces intrinsic apoptosis in ESCC cells. We found that lapachol strongly attenuates downstream signaling molecules of RSK2 in ESCC cells and also directly inhibits RSK2 activity in vitro . The RSK protein is highly activated in ESCC cells and knockdown of RSK2 significantly suppresses anchorage‐dependent and anchorage‐independent growth of ESCC cells. Additionally, lapachol inhibits anchorage‐dependent and anchorage‐independent growth of ESCC cells, and the inhibition of cell growth by lapachol is dependent on the expression of RSK2. We also found that lapachol induces mitochondria‐mediated cellular apoptosis by activating caspases‐3, ‐7, and PARP, inducing the expression of cytochrome c and BAX by inhibiting downstream molecules of RSK2. Overall, lapachol is a potent RSK2 inhibitor that might be used for chemotherapy against ESCC.