Anti-metastatic effect of jolkinolide B and the mechanism of activity in breast cancer MDA-MB-231 cells

Abstract

Abstract. Tumor metastasis is the main cause of mortality in cancer patients. However, no effective therapies are currently available to prevent metastasis. Cell adhesion to the extracellular matrix (ECM) is crucial in cancer progression and metastasis. Thus, suppression of cell adhesion may be an effective therapeutic strategy for the prevention of metastasis. In the present study, the anti-adhesion and anti-invasion effects of jolkinolide B, a diterpenoid compound from Euphorbia fischeriana Steud, that were exerted through suppression of β 1 -integrin expression and phosphorylation of focal adhesion kinase (FAK) were examined in human breast cancer MDA-MB-231 cells. Jolkinolide B inhibited the adhesion of MDA-MB-231 cells to fibronectin but not to poly-L-lysine. In addition, jolkinolide B inhibited extracellular signal-regulated kinase (ERK) phosphorylation. U0126, an ERK inhibitor, also suppressed the invasion and adhesion of MDA-MB-231 cells. Overall, the present data demonstrated that jolkinolide B is a novel inhibitor of FAK-mediated signaling pathways that is involved in decreasing cell adhesion and invasion. Mitogen-activated protein kinase/ERK kinase may play a critical role in these effects, indicating that jolkinolide B possesses therapeutic potential for the treatment of breast cancer metastasis.

Jolkinolide B induces apoptosis and inhibits tumor growth in mouse melanoma B16F10 cells by altering glycolysis

“…It has been reported that JB regulates proliferation and induces apoptosis in human leukemic U937 cell7. Another document evaluates the anti-metastatic role and mechanisms of JB on breast cancer MDA-MB-231 cells by the integrin/FAK and ERK pathways in vitro 8.…”

Jolkinolide B induces apoptosis of colorectal carcinoma through ROS-ER stress-Ca2+-mitochondria dependent pathway

“…In past decades, many natural products including berberine [ 21 ], resveratrol [ 22 ] and quercetin [ 23 ] were found to exhibit significant anti-cancer effects and thus were applied in clinic. Jolkinolide B, a diterpenoid compound isolated from the dried plant roots of Euphorbia Fscheriana Steud, has previously been reported to have anticancer effects on cancer, such as inhibiting the proliferation of mouse melanoma [ 13 ], inducing the apoptosis of breast cancer [ 24 , 25 ] and prostate cancer [ 26 ], and suppressing the metastatic activity of breast cancer cells [ 10 ]. As determined here, the IC50 of JB against CRC (18.25–38 µM, 48 h) is comparable to or smaller than those well-known promising agents including resveratrol (164.7 μM, 48 h) [ 27 ], quercetin (81.65 ± 0.49 μM, 48 h) [ 28 ] or some first line chemotherapy (5-FU, 92.85 µM, 72 h) [ 29 ], we speculate that JB could be a potential anticancer agent for CRC treatment.…”

“…Jolkinolide B (JB) is a bioactive diterpenoid component isolated from the dried roots of Euphorbia fischeriana Steud. It has been reported that JB exhibited anti-adhesion and anti-invasion effects in human breast cancer MDA-MB-231 cells through the suppression of β1-integrin expression and the phosphorylation of focal adhesion kinase (FAK) [ 10 ]. Moreover, JB can induce apoptosis in human chronic myeloid leukemia [ 11 , 12 ] via decreasing PI3K/Akt and the inhibitor of apoptosis protein (IAP) family proteins, and activating caspase-3 and -9.…”

Anti-Cancer Activities of Diterpenoids Derived from Euphorbia fischeriana Steud

“…Fortunately many plant-derived compounds have been discovered to effectively suppress metastasis of tumor cells [ 47 , 48 , 49 ]. Compound 1 was found to inhibit the attachment of MDA-MB-231 cells to fibronectin, with these effects being mediated by the integrin/FAK and ERK pathways [ 50 ]. Compound 8 has been demonstrated to inhibit VEGF-induced angiogenesis by targeting the VEGFR-2 signaling pathway [ 51 ].…”