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Sanguinarine Induces Apoptosis of Human Oral Squamous Cell Carcinoma KB Cells via Inactivation of the PI3K/Akt Signaling Pathway
Author(s) -
Lee Tae Kyung,
Park Cheol,
Jeong SoonJeong,
Jeong MoonJin,
Kim GiYoung,
Kim WunJae,
Choi Yung Hyun
Publication year - 2016
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21315
Subject(s) - sanguinarine , apoptosis , protein kinase b , pi3k/akt/mtor pathway , biology , microbiology and biotechnology , signal transduction , caspase , cytochrome c , programmed cell death , caspase 3 , cancer research , kinase , phosphorylation , chemistry , biochemistry , alkaloid , botany
Preclinical ResearchSanguinarine, an alkaloid isolated from the root of Sanguinaria canadensis and other plants of the Papaveraceae family, selectively induces apoptotic cell death in a variety of human cancer cells, but its mechanism of action requires further elaboration. The present study investigated the pro‐apoptotic effects of sanguinarine in human oral squamous cell carcinoma KB cells. Sanguinarine treatment increased DR5/TRAILR2 (death receptor 5/TRAIL receptor 2) expression and enhanced the activation of caspase‐8 and cleavage of its substrate, Bid. Sanguinarine also induced the mitochondrial translocation of pro‐apoptotic Bax, mitochondrial dysfunction, cytochrome c release to the cytosol, and activation of caspase‐9 and ‐3. However, a pan‐caspase inhibitor, z‐VAD‐fmk, reversed the growth inhibition and apoptosis induced by sanguinarine. Sanguinarine also suppressed the phosphorylation of phosphoinositide 3‐kinase (PI3K) and Akt in KB cells, while co‐treatment of cells with sanguinarine and a PI3K inhibitor revealed synergistic apoptotic effects. However, pharmacological inhibition of AMP‐activated protein kinase and mitogen‐activated protein kinases did not reduce or enhance sanguinarine‐induced growth inhibition and apoptosis. Collectively, these findings indicate that the pro‐apoptotic effects of sanguinarine in KB cells may be regulated by a caspase‐dependent cascade via activation of both intrinsic and extrinsic signaling pathways and inactivation of PI3K/Akt signaling. Drug Dev Res 77 : 227–240, 2016. © 2016 Wiley Periodicals, Inc.