Forskolin exerts anticancer roles in non-Hodgkin’s lymphomas via regulating Axin/β-catenin signaling pathway
Received 19 July 2018
Accepted for publication 10 January 2019
Published 19 February 2019 Volume 2019:11 Pages 1685—1696
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Beicheng Sun
Hailei Wang,1 Chunyan Lou,1 Na Ma2
1Department of Pediatrics, Huaihe Hospital of Henan University, Kaifeng, Henan, China; 2Department of Neurology, Henan Kaifeng Children’s Hospital, Kaifeng, Henan, China
Background: Non-Hodgkin’s lymphomas (NHLs) account for 85% of lymphomas, which are characterized by high-degree malignancy, rapid progress, and even invasion into central nervous system in pediatric patients. Although the cure rate of pediatric NHL has improved, some patients have still underwent recurrence or death. This study focuses on the effects and mechanism of forskolin on the progression of NHL, aiming to find efficient therapy methods for pediatric NHL.
Methods: MTT, flow cytometry and mice tumor bearing experiments were used to evaluate the effects of forskolin on NHL cell proliferation, apoptosis and tumorigenesis. Western blotting and RT-PCR assays were used to detect protein and mRNA expression. Immunohistochemistry technology was recruited to analyze Ki-67 expression in tumor tissues.
Results: Forskolin significantly increased the expression of cleaved caspase-3/9 in both NHL Toledo and NK-92 cell lines, and inhibited cell growth. Besides, forskolin obviously reduced the expression of β-catenin protein, promoted its ubiquitination, enhanced its transportation from nuclear to cytoplasm, as well as decreased the expression of its downstream oncogenes c-myc and cyclin D1 through upregulating Axin expression and stability and inhibiting Axin ubiquitination. Moreover, forskolin enhanced the effects of SP600125, an inhibitor of c-Jun N-terminal kinase signaling on cell apoptosis promotion and tumorigenesis inhibition via Axin-induced β-catenin signaling repression.
Conclusion:The current study clarifies that forskolin can inhibit the progression of NHL through Axin-mediated inhibition of β-catenin signaling. Moreover, forskolin improves the effects of SP600125 on cell apoptosis enhancement and tumorigenesis inhibition of NHL cells. These findings provide theoretical foundation of serving forskolin as a new effective therapeutic drug for pediatric NHL.
Keywords: forskolin, SP600125, Axin, β-catenin, carcinogens
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