Arsenic trioxide induces autophagy and antitumor effects in Burkitt’s lymphoma Raji cells

Abstract

Although it is generally acknowledged that auto-phagy plays an important role in tumorigenesis and therapy, studies of autophagy in different cell types and under different conditions have led to conflicting theories regarding the influence of autophagy on cell death. In the present study, we explored the role of autophagy and its underlying mechanism in the inhibitory effects of arsenic trioxide (As2O3) on Burkitt's lymphoma Raji cells. The results showed that As2O3 significantly inhibited the proliferation of Raji cells in a dose- and time-dependent manner, induced G2/M phase cell cycle arrest and apoptosis. Moreover, As2O3 also promoted the formation of autophagic vacuoles, as well as increased the degradation of autophagy substrate P62 protein, which was accompanied by an upregulation of Beclin-1 gene and a downregulation of Bcl-2 gene expression. 3-Methyladenine, an autophagy inhibitor, not only increased cell viability through inhibiting autophagic cell death and apoptosis, but also reversed the upregulation of Beclin-1 gene and the downregulation of Bcl-2 gene in the Raji cells induced by As2O3. These results may lead to a better understanding of the action of As2O3 and may provide evidence that autophagy plays an important role in the regulation of cell death. Therefore, regulation of autophagic activity may be a promising therapy for patients with Burkitt's lymphoma.

Autophagy in Cancer Cell Death

“…Arsenic trioxide was shown to induce ACD and cell death in various tumor cell populations in multiple studies, including our own [14,[56][57][58]. Considering that arsenic trioxide is already clinically used to treat acute promyelocytic leukemia (APL) [59] and easily crosses the blood-brain-barrier [60], this drug could be particularly interesting for hard-to-treat cancers, such as brain tumors (primary or metastases).…”

Differences of basic and induced autophagic activity between K562 and K562/ADM cells

“…Subsequently, cells were gently washed with PBS three times and observed under an IX81 inverted kit. Equal amounts of protein from cell extracts were separated by SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) and transferred onto a PVDF (polyvinylidene fluoride) membrane (30). The membrane was incubated with primary antibodies overnight at 4℃ and then with secondary antibodies conjugated with horseradish peroxidase.…”

Insulin resistance contributes to multidrug resistance in HepG2 cells via activation of the PERK signaling pathway and upregulation of Bcl-2 and P-gp

“…The morphological features were assessed using electron microscopy (15). Briefly, HepG2 and HepG2/IR cells were immobilized in 3% glutaraldehyde, embedded and sectioned.…”

“…Cells were then washed with phosphate-buffered saline (PBS) and stained with PI for 30 min at room temperature in the dark. Cell cycle analysis was performed with a Coulter Epics XL flow cytometer (15).…”