@inproceedings{856775dfa0094af38c540374ae613663,
title = "Potential inhibition of PDK1/Akt signaling by phenothiazines suppresses cancer cell proliferation and survival",
abstract = "3′-Phosphoinositide-dependent kinase-1 (PDK1) has been identified for its ability to phosphorylate and activate Akt. Accumulated studies have shown that the activation of the PDK1/Akt pathway plays a pivotal role in cell survival, proliferation, and tumorigenesis. Therefore, the PDK1/Akt pathway is believed to be a critical target for cancer intervention. In this paper, we report the discovery of a new function of phenothiazines, widely known as antipsychotics, inhibiting PDK1/Akt pathway. Upon epidermal growth factor (EGF) stimulation, phenothiazines specifically suppressed the kinase activity of PDK1 and the phosphorylation level of Akt. The inhibition of PDK1/Akt kinase resulted in suppression of EGF-induced cell growth and induction of apoptosis in human ovary cancer cells. In particular, phenothiazines were highly selective for downstream targets of PDK1/Akt and did not inhibit the activation of phosphatidylinositol 3-kinase (PI3K), EGFR, or extracellular signal-regulated kinase 1/2 (ERK1/2). In particular, phenothiazines effectively suppressed tumor growth in nude mice of human cancer cells. Taken together, these findings provide strong evidence for novel function of phenothiazines, pharmacologically targeting PDK1/Akt for anticancer drug discovery.",
keywords = "Akt, Apoptosis, Cancer cells, PDK1, Phenothiazines, Proliferation",
author = "Choi, {Jang Hyun} and Yang, {Yong Ryoul} and Lee, {Seul Ki} and Kim, {Sun Hee} and Kim, {Yun Hee} and Cha, {Joo Young} and Oh, {Se Woong} and Ha, {Jong Ryul} and Ryu, {Sung Ho} and Suh, {Pann Ghill}",
note = "Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2008",
month = sep,
doi = "10.1196/annals.1414.041",
language = "English (US)",
isbn = "9781573317009",
series = "Annals of the New York Academy of Sciences",
publisher = "Blackwell Publishing Inc.",
pages = "393--403",
booktitle = "Recent Advances in Clinical Oncology",
}