Bakkenolide A inhibits leukemia by regulation of HDAC3 and PI3K/Akt-related signaling pathways.

Bakkenolide A inhibits leukemia by regulation of HDAC3 and PI3K/Akt-related signaling pathways. Biomed Pharmacother. 2016 Aug 11;83:958-966 Authors: Zhang L, Hong Z, Zhang RR, Sun XZ, Yuan YF, Hu J, Wang X Abstract Leukemia has been the third type of cancer killing many people across the world. Bakkenolide A (Bak), extracted from Petasites tricholobus, has been suggested to against cancer and display protective effects on inflammatory cytokines formation. And increasing evidences suggest that histone deacetylase 3 (HDAC3) plays vital roles in cancer formation and persistence via cell death, apoptosis and inflammation. But the function of Bakkenolide A in regulating leukemia is not understood yet, particularly via HDAC3. Here, we found that HDAC3 is up-regulated in clinical samples of leukemia compared with adjacent normal tissues. Then the expression of HDAC3 was knocked down via RNA interference in K562 cells. And inhibition of HDAC3 expression is able to improve leukemia invasion, migration and proliferation. Further, we also found HDAC3 bound to IκBα, affecting subsequent inflammation response. Moreover, Bakkenolide A was found to inhibit inflammation, induce apoptosis and cell death in leukemia cells via PI3K-regulated signaling pathway, down-regulating IKKs expression and suppressing in proinflammatory cytokines of IL-1β, IL-18 and TNF-α. Up-regulation of Caspase3/7 was observed in cells of HDAC3-knockdown and Bakkenolide A ...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research