Lapachol is a novel ribosomal protein S6 kinase 2 inhibitor that suppresses growth and induces intrinsic apoptosis in esophageal squamous cell carcinoma cells

Xueyin Zu, Xiaomeng Xie, Yuanyuan Zhang, Kangdong Liu, Ann M. Bode, Zigang Dong, Dong Joon Kim

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2337-2346
Number of pages10
JournalPhytotherapy Research
Volume33
Issue number9
DOIs
StatePublished - Sep 1 2019

Bibliographical note

Funding Information:
Key program of Henan Province, China, Grant/ Award Number: 161100510300; National Natural Science Foundation China, Grant/ Award Number: 81572812; Henan Joint Fund, Grant/Award Number: U1804196

Funding Information:
This work was supported by Henan Joint Fund, National Natural Science Foundation China (NSFC; U1804196 and 81572812) and Key program of Henan Province, China (161100510300).

Publisher Copyright:
© 2019 John Wiley & Sons, Ltd.

Keywords

  • RSK2
  • apoptosis
  • esophageal squamous cell carcinoma
  • lapachol

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