Wogonin induces apoptosis and endoplasmic reticulum stress in HL-60 leukemia cells through inhibition of the PI3K-AKT signaling pathway.

Abstract

Wogonin is a flavonoid isolated from Scutellaria baicalensis root and has multiple pharmacological effects, including anticancer effects. Recent studies have shown that wogonin induces cell cycle arrest and reverses multi-drug resistance in the human K562 leukemia cell line. However, its pharmacological function in the apoptosis of leukemia cells remains unknown. Therefore, we hypothesized that wogonin can induce apoptosis in the HL-60 leukemia cell line. In the present study, the HL-60 cells were treated with different doses of wogonin (0-150 µM). Wogonin inhibited the viability of HL-60 cells in a dose-dependent and time-dependent manner. Flow cytometry and analyses of caspase and PARP-1 activation and the Bax/Bcl-2 ratio, demonstrated that the cytotoxic effect of wogonin on HL-60 cells was mediated by caspase-dependent and mitochondrial-dependent apoptosis. Wogonin also induced the expression of certain members of the endoplasmic reticulum (ER) stress pathway (CHOP, GRP94 and GRP78) and the activation of multiple branches of ER stress transducers (IRE1α, PERK-eIF2α and ATF6) in the HL-60 cells. In addition, wogonin reduced the phosphorylation of PI3K and AKT in the HL-60 cells. Furthermore, constitutive activation of AKT induced by adenoviral vectors inhibited the pro-apoptotic effects and ER stress induced by wogonin in the HL-60 cells. In summary, our results indicated that wogonin induced apoptosis and ER stress in HL-60 cells, which was mediated by the inhibition of the PI3K-AKT signaling pathway.

• Authors: Chengjun Hu, Maozhong Xu, Rujuan Qin, Weifeng Chen, Xin Xu
• Journal: Oncology reports (Oncol Rep) Vol. 33 Issue 6 Pg. 3146-54 (Jun 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25846394 (Publication Type: Journal Article)

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• Flavanones
• HSPA5 protein, human
• Neoplasm Proteins
• Reactive Oxygen Species
• Oncogene Protein v-akt
• wogonin

Topics

• Animals
• Apoptosis (drug effects)
• Cell Proliferation
• Drug Resistance, Multiple (genetics)
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (drug effects)
• Flavanones (administration & dosage)
• Gene Expression Regulation, Leukemic (drug effects)
• HL-60 Cells
• Humans
• Leukemia (drug therapy, genetics, pathology)
• Neoplasm Proteins (biosynthesis, genetics)
• Oncogene Protein v-akt (biosynthesis, genetics)
• Phosphatidylinositol 3-Kinases (biosynthesis, genetics)
• Reactive Oxygen Species
• Signal Transduction (drug effects)