| In vitro: |
| Mol Cancer Ther. 2009 Apr;8(4):873-82. | | ExcisaninA, a diterpenoid compound purified from Isodon MacrocalyxinD, induces tumor cells apoptosis and suppresses tumor growth through inhibition of PKB/AKT kinase activity and blockade of its signal pathway.[Pubmed: 19372560 ] | Isodon diterpenoids have received considerable phytochemical and biological attention for their strong antitumor activity with low toxicity.
METHODS AND RESULTS:
In this study, Excisanin A, a diterpenoid compound purified from Isodon Macrocalyxin D, was tested on human Hep3B and MDA-MB-453 cell lines and Hep3B xenograft models. The results showed Excisanin A could inhibit the proliferation of Hep3B and MDA-MB-453 cells via induction of apoptosis, with the evidence of increasing AnnexinV-positive cells and characteristic morphologic changes of apoptosis in the nucleus. Also, Excisanin A sensitized Hep3B cells to 5-fluorouracil treatment or MDA-MB-453 cells to ADM treatment in vitro. In Hep3B xenograft models, Excisanin A at 20 mg/kg/d remarkably decreased the xenograft tumor size and induced tumor cells apoptosis using transferase-mediated FITC-12-dUTP nick-end labeling assay. More importantly, we found that Excisanin A could inhibit AKT activity and block its signal pathway in vitro and in vivo. And treatment with Excisanin A significantly reduced the number of viable cells in Hep3B/myr-AKT1 cells more than that in control cells.
CONCLUSIONS:
Together, Excisanin A might be a potent inhibitor of AKT signaling pathway in tumor cells. These data provide validation for the development of Excisanin A to treat cancers displaying elevated levels of AKT. | | Planta Med. 2001 Jul;67(5):406-10. | | Kaurane diterpenes from Isodon japonicus inhibit nitric oxide and prostaglandin E2 production and NF-kappaB activation in LPS-stimulated macrophage RAW264.7 cells.[Pubmed: 11488452] |
METHODS AND RESULTS:
A methanolic extract of the whole plant of Isodon japonicus (Labiatae) showed potent inhibition on the LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW264.7 cells. Four known kaurane diterpenes were isolated by activity-guided fractionation and their structures were identified as kamebanin (1), kamebacetal A (2), kamebakaurin (3), Excisanin A (4). All compounds also inhibited the LPS-induced NF-kappaB activation as assessed by NF-kappaB reporter assay and electrophoretic mobility shift assay (EMSA). Compounds 2-4 showed comparable inhibitory effects on the LPS-induced production of NO and PGE2, and activation of NF-kappaB without affecting cell viability.
CONCLUSIONS:
These results suggest that kaurane diterpenes could exert their inhibitory effects on the production of NO and PGE2 through the suppression of NF-kappaB activation, and be partially responsible for the anti-inflammatory activities of the genus Isodon. |
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Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
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