Shikonin exerts antitumor activity in Burkitt's lymphoma by inhibiting C-MYC and PI3K/AKT/mTOR pathway and acts synergistically with doxorubicin

Scientific Reports
Fan NiXiangmin Tong

Abstract

Burkitt's lymphoma (BL) is a highly aggressive malignancy molecularly characterized by deregulation of the C-MYC proto-oncogene. Recently, it has been confirmed that phosphatidylinositol-3-kinase (PI3K) pathway activation is a crucial element in the malignant transformation of the B cells in BL. Despite the better outcome of adults with BL treated with high-intensity chemotherapy regimens, the overall survival rate for patients older than 60 years remains dismal. Shikonin, a natural naphthoquinone derived from Chinese herbal medicine plant, has the potential to induce cell death in a series of human cancer. In the present study, we investigated the effect and molecular mechanisms of Shikonin in treatment with BL. Shikonin suppressed cellular proliferation and induced caspase-dependent apoptosis in BL cells. Inhibition of C-MYC and suppression of PI3K/AKT/mTOR pathway played critical roles in SHK-induced apoptosis in BL both in vitro and in vivo. Besides, Shikonin potentiated doxorubicin-induced growth inhibition and apoptosis in vitro. Furthermore, the growth of a subcutaneous xenograft tumor model of BL was significantly inhibited by shikonin. Importantly, we did not find the effect of shikonin on liver function in mice. In su...Continue Reading

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Citations

Feb 29, 2020·Journal of Hepatocellular Carcinoma·Tong LiuChuanyong Guo
Jun 26, 2020·Frontiers in Pharmacology·Fangfang WangJinshan Tang
Aug 15, 2018·Histochemistry and Cell Biology·Dariusz Stępiński
Nov 18, 2020·Current Cancer Drug Targets·Junqi CuiJun Chen
Aug 20, 2020·Mini Reviews in Medicinal Chemistry·Esmaeil Sheikh AhmadiAmirhossein Sahebkar

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Methods Mentioned

BETA
xenograft
flow cytometry
Fluorescence microscopy
xenografts
Protein Assay
PCR

Software Mentioned

CalcuSyn

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