Cucurbitacin B synergistically enhances the apoptosis-inducing effect of arsenic trioxide by inhibiting STAT3 phosphorylation in lymphoma Ramos cells

Abstract

Arsenic trioxide (ATO) is a classic apoptosis-inducing agent used to treat acute promyelocytic leukemia. However, the therapeutic effect of ATO is limited in lymphoma, which resists apoptosis possibly due to inappropriate activation of STAT3. Therefore, combination of ATO and STAT3 inhibitor may be a potential strategy to treat lymphoma. Dramatically, Cucurbitacin B (CuB), an effective component of the dichloromethane extraction from Trichosanthes kirilowii Maxim, synergistically eliminated the apoptosis resistance of Burkitt’s lymphoma Ramos cells to ATO by inhibiting the phosphorylation of STAT3, followed in turn by downregulation of Bcl-2 and upregulation of Bax. Furthermore, CuB and ATO in combination have no pro-apoptotic effect on normal lymphatic cells, indicating the absence of toxicity to hematological cells. This synergistic effect was further confirmed in nude murine lymphoma model, which exhibited significant apoptosis induction and tumor growth inhibition. Collectively, CuB synergistically enhances the apoptosis-inducing effect of ATO by inhibiting STAT3 phosphorylation in Ramos cells.

Keywords:

• Trichosanthes kirilowii Maxim
• Cucurbitacin B
• Burkitt’s lymphoma
• apoptosis
• arsenic trioxide

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Nos. 81473441 and 81503383) and the Tianjin Application Foundation and Advanced Technology Research Plan (13JCQNJC1380).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2017.1289521.