Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells

Ji Yeon Lim; Joo Yun Lee; Byung Jin Byun; Seong Hwan Kim

doi:10.1016/j.toxrep.2015.07.004

Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells

Toxicol Rep. 2015 Jul 13:2:984-989. doi: 10.1016/j.toxrep.2015.07.004. eCollection 2015.

Authors

Ji Yeon Lim^{1

2}, Joo Yun Lee³, Byung Jin Byun³, Seong Hwan Kim^{1

2}

Affiliations

¹ Laboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
² Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
³ Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.

Abstract

Aberrant regulation of phosphatidylinositol-3-kinases (PI3Ks) is known to be involved in the progression of cancers. PI3K-binding flavonoids such as quercetin and myricetin have been shown to inhibit PI3K activity, but the direct targeting of fisetin to PI3K has not been established. Here, we carried out an in silico investigation of fisetin binding to PI3K and determined fisetin's inhibitory activity in enzymatic and cell-based assays. In addition, fisetin induced apoptosis in human Burkitt's lymphoma Raji cells by inhibiting both PI3Ks and mammalian target of rapamycin (mTOR). Our results indicate that fisetin may serve as a natural backbone for the development of novel dual inhibitors of PI3Ks and mTOR for the treatment of cancer.

Keywords: Apoptosis; Burkitt’s lymphoma; Fisetin; Fisetin (CID: 5281614); PI3K; mTOR.