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Leuk Lymphoma. 2017 Oct;58(10):2439-2451. doi: 10.1080/10428194.2017.1289521. Epub 2017 Feb 20.

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

Ding X1,2, Chi J1,2, Yang X1,2, Hao J1,2, Liu C1,2, Zhu C1,2, Wang X1,2, Liu X1,2, Niu Y1,2, Ji W3, Chen D4, Wu X1,2.

Author information

1
a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.
2
b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
3
c Opening Cancer Laboratory , Tianjin Medical University Cancer Institute and Hospital , Tianjin , China.
4
d Department of Pharmacology , Basic Medical College, Tianjin Medical University , Tianjin , China.

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:

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

PMID:
28278714
DOI:
10.1080/10428194.2017.1289521
[Indexed for MEDLINE]

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