Abstract
Purpose: To investigate the effect of isoliquiritigenin (ISL) on diffuse large B-cell lymphoma (DLBCL) cells and its underlying mechanism of action.Methods: The DLBCL cell line OCI-Ly19 was used in this study. Cell proliferation was measured by MTT assay. Apoptosis was evaluated using flow cytometry. Phosphorylation of Akt and mTOR was assessed using Western blotting.Results: DLBCL cell proliferation was suppressed by ISL in a concentration-dependent manner. The number of apoptotic cells increased following ISL treatment in a concentration-dependent manner (p < 0.05). ISL treatment also stopped the cell cycle at the G1 phase in a concentration-dependent manner. Western blot analysis indicated that there was no significant Akt and mTOR expression in cells treated with 10, 20, or 50 μM ISL (p < 0.05). However, Akt and mTOR phosphorylation was upregulated following treatment with 10, 20, or 50 μM ISL in a concentration-dependent manner (p < 0.05).Conclusion: The results demonstrate that ISL inhibits DLBCL cell proliferation and promotes cell apoptosis by blocking the cell cycle transition from the G1 to S phase, which is mediated by the inactivation of the Akt/mTOR signaling pathway.
 Keywords: Isoliquiritigenin, Cell survival, Diffuse large B-cell lymphoma, Akt/mTOR signaling pathway
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common among lymphoid neoplasms and accounts for 30% of non-Hodgkin lymphomas in adults [1]
Results from the present study indicate that in a DLBCL cell line, ISL reduced cell proliferation, induced cell apoptosis, and reduced cell cycle transition from G1 to S phase
The resulting cell cycle arrest in the G1 phase was mediated by inactivation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway, indicating the therapeutic possibility of ISL in the treatment of DLBCL
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common among lymphoid neoplasms and accounts for 30% of non-Hodgkin lymphomas in adults [1]. DLBCL is defined as a malignancy with a diffuse pattern of large B-cells [2]. The standard therapeutic regimen for DLBCL has remained largely unchanged for over 25 years, with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy still in use [4]. With the addition of rituximab (R) to CHOP, the 6-year event-free survival has increased from 55.8% to 74.3%, greatly improving the long-term prognosis for young patients with DLBCL [5]. The 5-year event-free survival was only 47% in elderly patients with DLBCL [6]. A new therapeutic strategy is required to further extend the longterm survival of DLBCL patients
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