In Vitro Antitumor Activity of Stellettin B, a Triterpene from Marine Sponge Jaspis stellifera, on Human Glioblastoma Cancer SF295 Cells

Abstract

Stellettin B was isolated from marine sponge Jaspis stellifera. In vitro antitumor activities were investigated on 39 human cancer cell lines. Stellettin B exhibited highly potent inhibition against the growth of a human glioblastoma cell line SF295, with a GI50 of 0.01 μM. In contrast, stellettin B showed very weak inhibitory activity on normal cell lines including HMEC, RPTEC, NHBE and PrEC, with GI50s higher than 10 μM, suggesting its relatively selective cytotoxicity against human cancer cells compared to normal human cell lines. We then focused on the antitumor activity of this compound on SF295 cells. Flow cytometric analysis indicated that stellettin B induced apoptosis in SF295 cells in a concentration-dependent manner. Further study indicated that stellettin B increased the production of ROS, the activity of caspase 3/7, as well as the cleavage of PARP, each of which is known to be involved in apoptosis. To investigate the molecular mechanism for cell proliferation inhibition and apoptosis induction, effect on the phosphorylation of several signal proteins of PI3K/Akt and RAS/MAPK pathways was examined. Stellettin B inhibited the phosphorylation of Akt potently, with no activity on p-ERK and p-p38, suggesting that inhibition of PI3K/Akt pathway might be involved in the antiproliferative and apoptosis-inducing effect. However, homogenous time-resolved fluorescence (HTRF) assay indicated that stellettin B did not inhibit PI3K activity, suggesting that the direct target might be signal protein upstream of Akt pathway other than PI3K.

Stellettin B Induces G1 Arrest, Apoptosis and Autophagy in Human Non-small Cell Lung Cancer A549 Cells via Blocking PI3K/Akt/mTOR Pathway

“…We previously reported that Stel B inhibited phosphorylation of Akt in SF295 cells15. Therefore, the effect of Stel B on Akt pathway was examined in A549 cells.…”

Sinularin induces oxidative stress‐mediated G2/M arrest and apoptosis in oral cancer cells

“…In the example of marine sponges, ROS‐mediated apoptosis was induced by 10‐acetylirciformonin B from Ircinia sp. for leukemia HL 60 cells, stellettin B from Jaspis stellifera for glioblastoma cancer SF295 cells, and Polymastia janeirensis extracts for U138MG glioma cells . Therefore, the ROS modulating effect of marine natural products may induce apoptosis for anticancer cells.…”

Drugs from Marine Sources: Modulation of TRAIL Induced Apoptosis in Cancer Cells

“…In-vitro assays revealed Stellettin B induced ROS generation in glioblastoma cancer SF295 cells. Phosphorylated Akt levels were also remarkably reduced in Stellettin B treated SF295 cells (Tang et al, 2014). JG6, is a marine-derived oligosaccharide.…”