Ridaifen-SB8, a novel tamoxifen derivative, induces apoptosis via reactive oxygen species-dependent signaling pathway

Guo, Wen Zhi; Shiina, Isamu; Wang, Yanwen; Umeda, Eri; Watanabe, Chihiro; Uetake, Shoko; Ohashi, Yoshimi; Yamori, Takao; Dan, Shingo

doi:10.1016/j.bcp.2013.08.020

Cited by 10 publications

(13 citation statements)

References 53 publications

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“…To confirm the apoptosis-inducing activity of stellettin B and investigate the related mechanism on SF295 cells, we determined caspase 3/7 activity in SF295 cells with or without stellettin B treatment by using Caspase-Glo assay [8]. As shown in Figure 5A, caspase 3/7 activity increased concentration-dependently in stellettin B treated SF295 cells, supporting that apoptosis was induced by stellettin B. Staurosporine (STA), which is known as an apoptosis-inducing agent [9] and therefore used as positive control, also increased caspase 3/7 activity significantly at 0.1 μM.…”

Section: Resultsmentioning

confidence: 99%

“…Annexin V and PI staining assay was conducted to detect apoptosis as well as the stage of that induced by stellettin B, as described by us previously [8]. Briefly, SF295 cells grown in 12-well plates after treatment with various concentrations of stellettin B were collected, washed with PBS twice, stained with 5 μL of Annexin V-FITC and 5 μL of PI (5 μg/mL) in binding buffer for 15 min at room temperature in the dark, and analyzed by flow cytometer (FACS Calibur, Beckton Dickinson, Franklin Lakes, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Caspase-Glo 3/7 assay was carried out as described by us previously [8] but with a small modification. One hundred μL of SF295 cell suspension was planted in the wells of a white 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

“…ROS production was determined by staining the cells with CM-H 2 DCFDA (Thermo Fisher, Waltham, MA, USA) [8]. After treatment with various concentrations of stellettin B for 24 h under a 5% CO 2 atmosphere at 37 °C, cells were incubated with 10 μM CM-H 2 DCFDA for 30 min.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2014

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

et al. 2014

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“…It has been reported that RID-SB8 preferentially induced cell death in human breast cancer cell lines, MCF-7 and MDA-MB-231, over normal human mammary epithelial cells (18). Although the detailed mechanism for the anti-proliferative effect of RID-B on cancer cells is as yet unclear, the efficacy of RID-B may be dependent on cell growth rate.…”

Section: Discussionmentioning

confidence: 99%

Anti‑proliferative effect of ridaifen‑B on hepatoma cells

et al. 2018

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Abstract. Ridaifens (RIDs), a novel series of tamoxifen derivatives, exhibit a potent growth-inhibitory effect against numerous tumor cells regardless of the expression of estrogen receptors, and are thus promising candidates as novel anti-tumor drugs. RID-B is a first generation RIDs, and inhibits the proliferation of several tumor cell lines. However, the potentially growth inhibitory effect of RID-B against hepatoma cells, and the detailed mechanism underlying RID-B-mediated tumor cell death remain to be elucidated. The purpose of the current study was to evaluate the anti-proliferative effect of RID-B against hepatoma cells. The anti-proliferative effect of RID-B against human hepatoma Huh-7 cells was investigated by cell proliferation assay using WST-1 reagent, and caspase-3 activity was evaluated by using specific fluorescent substrate. In addition, DNA fragmentation in Huh-7 cells induced by RID-B was estimated by terminal deoxynucleotidyl transferase dUTP nick-end labelling assay, and binding of RID-B to double-stranded DNA was confirmed by mass spectrometry. RID-B (0.5, 1 and 2 µM) inhibited the growth of Huh-7 cells, seemingly dose-dependently, but did not inhibit the growth of normal primary rat hepatocytes in the same concentration range. Furthermore, the caspase-3 activity of Huh-7 cells was increased by RID-B (0.5 and 5 µM), and the anti-proliferative effect of RID-B (1 µM) on Huh-7 cells was partially suppressed by the addition of the caspase inhibitor, Z-VAD-FMK. Additionally, RID-B (10 µM) directly bound to double-stranded DNA, and the addition of DNA suppressed RID-B-mediated cell growth inhibition and DNA fragmentation in Huh-7 cells. From these data, it may be concluded that RID-B inhibited cell growth and induced apoptosis via activating caspase-3 and binding to DNA directly, leading to DNA fragmentation in hepatoma cells.

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Targeting breast cancer initiating cells: Advances in breast cancer research and therapy

McCubrey

Davis

Abrams

et al. 2014

Advances in Biological Regulation

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Ridaifen-SB8, a novel tamoxifen derivative, induces apoptosis via reactive oxygen species-dependent signaling pathway

Cited by 10 publications

References 53 publications

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

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

Anti‑proliferative effect of ridaifen‑B on hepatoma cells

Targeting breast cancer initiating cells: Advances in breast cancer research and therapy

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