| Description: |
Jolkinolide B has potent anti-inflammatory, and antitumor activities, it is able to enhance apoptosis of human leukemic HL-60 and THP-1 cells, at least in part, through downregulation of JAK2/STAT3 and bcl-2, and upregulation of Bax and cytosolic cytochrome c. Jolkinolide B can induce neuroendocrine differentiation of human prostate LNCaP cancer cell line, it also can induce apoptosis in MDA-MB-231 cells through inhibition of the PI3K/Akt signaling pathway. |
| In vitro: |
| Biochem Biophys Res Commun. 2014 Mar 7;445(2):282-8. | | Jolkinolide B inhibits RANKL-induced osteoclastogenesis by suppressing the activation NF-κB and MAPK signaling pathways.[Pubmed: 24491533] | Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. The unique function and ability of osteoclasts to resorb bone makes them critical in both normal bone homeostasis and pathologic bone diseases such as osteoporosis and rheumatoid arthritis. Thus, new compounds that may inhibit osteoclastogenesis and osteoclast function may be of great value in the treatment of osteoclast-related diseases.
METHODS AND RESULTS:
In the present study, we examined the effect of Jolkinolide B (JB), isolated from the root of Euphorbia fischeriana Steud on receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. We found that Jolkinolide B inhibited RANKL-induced osteoclast differentiation from bone marrow macrophages (BMMs) without cytotoxicity. Furthermore, the expression of osteoclastic marker genes, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CtsK), and calcitonin receptor (CTR), was significantly inhibited. Jolkinolide Binhibited RANKL-induced activation of NF-κB by suppressing RANKL-mediated IκBα degradation. Moreover, Jolkinolide B inhibited RANKL-induced phosphorylation of mitogen-activated protein kinases (p38, JNK, and ERK).
CONCLUSIONS:
This study thus identifies Jolkinolide B as an inhibitor of osteoclast formation and provides evidence that Jolkinolide B might be an alternative medicine for preventing and treating osteolysis. | | Mol Cells. 2011 Nov;32(5):451-7. | | Jolkinolide B from Euphorbia fischeriana Steud induces apoptosis in human leukemic U937 cells through PI3K/Akt and XIAP pathways.[Pubmed: 22083305] | Jolkinolide B, a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud, is known to induce apoptosis in cancer cells. However, the molecular mechanism of its anti-cancer activity has not been fully elucidated.
METHODS AND RESULTS:
In the present study, we found that Jolkinolide B reduced cell viability and induced apoptosis in a dose- and time-dependent manner in human leukemic U937. The induction of apoptosis was also accompanied by the downregulation of PI3K/Akt and the inhibitor of apoptosis protein (IAP) family proteins. Moreover, we observed that Jolkinolide B treatment resulted in activation of caspase-3 and -9, which may partly explain the anti-cancer activity of Jolkinolide B.
CONCLUSIONS:
Taken together, our study for the first time suggest that Jolkinolide B is able to enhance apoptosis of U937 cells, at least in part, through downregulation of PI3K/Akt and IAP family proteins. Moreover, triggering of caspase-3 and -9 activation mediated apoptotic induction. |
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