Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.4.2.30 (
PARP
)
13,611
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Lapachol is a novel ribosomal protein S6 kinase 2 inhibitor that suppresses growth and induces intrinsic apoptosis in esophageal squamous cell carcinoma cells. 3122 74
