Novel TRAIL sensitizer <i>Taraxacum officinale</i>
 F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells

Yoon, Ji‐Yong; Cho, Hyun Soo; Lee, Jeong-Ju; Lee, Hyo‐Jung; Jun, Soo Young; Lee, Jae-Hye; Song, Hyuk‐Hwan; Choi, Sangho; Saloura, Vassiliki; Park, Choon Gil; Kim, Cheol-Hee; Kim, Nam-Soon

doi:10.1002/mc.22288

Cited by 35 publications

(20 citation statements)

References 27 publications

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“…To evaluate the mechanisms of tumor resistance to TRAIL and the ability of gelsolin to sensitize cells to TRAIL mediated cell death, we investigated human hepatoma (HepG2) and hepatocellular carcinoma (Huh7) cells exhibiting reduced sensitivity to TRAIL 19 . Previous studies have established reduced sensitivity of HepG2 and Huh7 cells to TRAIL 20 – 24 and subsequent analysis in our laboratory concurred with these results (data not shown) and allowed for selection of the TRAIL dose used in each cell line. Treatment of the cells with CM from IHH or TRAIL (25ng/ml for HepG2 and 50ng/ml for Huh7) alone induced modest (10–20%) cell death (Fig.…”

Section: Resultssupporting

confidence: 81%

N-terminal gelsolin fragment potentiates TRAIL mediated death in resistant hepatoma cells

Meyer

Kwon

Ray

et al. 2017

Sci Rep

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TNF-α related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells, without damaging normal cells. TRAIL receptors facilitate induction of apoptosis for selective elimination of malignant cells. However, some cancer cells have developed resistances to TRAIL which limits anticancer potential. Gelsolin, a multifunctional actin-binding protein, mediates cell death involving the TRAIL receptors in the hepatic stellate cell line, LX2. Here, we have shown that conditioned medium (CM) containing gelsolin fragments or an N-terminal gelsolin fragment (amino acid residues 1–70) in the presence of TRAIL impairs cell viability of TRAIL resistant transformed human hepatocytes (HepG2). Cell growth regulation by CM and TRAIL was associated with the modulation of p53/Mdm2, Erk and Akt phosphorylation status. The use of N-terminal gelsolin peptide1–70 alone or in combination with TRAIL, induced inhibition of Akt phosphorylation and key survival factors, Mdm2 and Survivin. Treatment of cells with an Akt activator SC79 or p53 siRNA reduced the effects of the N-terminal gelsolin fragment and TRAIL. Together, our study suggests that the N-terminal gelsolin fragment enhances TRAIL-induced loss of cell viability by inhibiting phosphorylation of Akt and promoting p53 function, effecting cell survival.

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Section: Resultssupporting

confidence: 81%

N-terminal gelsolin fragment potentiates TRAIL mediated death in resistant hepatoma cells

Meyer

Kwon

Ray

et al. 2017

Sci Rep

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“…It is widely acknowledged that ERK1/2, a subtype of mitogen-activated protein kinases (MAPKs), regulates cell proliferation, differentiation and migration through KIT-dependent pathways (36). JNK, another subtype of MAPKs that is expressed but not phosphorylated in GISTs in vitro (37), participates in the death receptor signaling pathway required for apoptosis induction in various cancers (38)(39)(40). Therefore, CBP is required for tumor growth through ERK1/2 phosphorylation and apoptosis regulation via inactivation of JNK in GIST882 cells, whereas p300 does not appear to contribute to these activities.…”

Section: Discussionmentioning

confidence: 99%

An inhibitor of the acetyltransferases CBP/p300 exerts antineoplastic effects on gastrointestinal stromal tumor cells

Wang

Zhou

et al. 2016

Oncology Reports

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm featured by activated mutations of KIT and PDGFRA. Although overall survival rates have greatly improved by the development of receptor tyrosine kinase inhibitors, most patients ultimately acquire resistance due to secondary mutations of KIT or PDGFRA. Inhibition of the histone acetyltransferases (HATs) CREB‑binding protein (CBP) and p300 results in antineoplastic effects in various cancers. To determine whether CBP/p300 can serve as an antineoplastic target for GISTs, specific short interfering RNA sequences and the selective HAT inhibitor C646 were administered to GIST882 cells. Cell viability, apoptosis and the cell cycle were analysed using the Cell Counting Kit-8, a caspase-3/7 activity assay or Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and PI staining. Gene and protein expression levels were measured by quantitative real-time polymerase chain reaction and western blotting, respectively. Transcriptional blockage of CBP, rather than p300, resulted in suppression of cell proliferation. Interestingly, both CBP and p300 depletion enhanced caspase-3/7 activity. A lack of CBP and p300 caused ETS translocation variant 1 (ETV1) downregulation and KIT inhibition in GIST cells. Nevertheless, the absence of CBP, not p300, leads to extracellular signal-regulated kinase 1/2 inactivation and c-Jun NH2-terminal kinase activation, suggesting a more crucial role for CBP than p300 in cell proliferation and survival. Furthermore, proliferation of GIST cells was reduced by administration of C646, a selective HAT inhibitor for CBP/p300. Apoptosis induction and cell cycle arrest were detected after exposure to C646, indicating that its antitumor activities were supported by its antiproliferative and proapoptotic effects. Additionally, C646 treatment attenuated ETV1 protein expression and inactivated KIT-dependent pathways. Taken together, the present study suggests that CBP/p300 may serve as novel antineoplastic targets and that use of the selective HAT inhibitor C646 is a promising antitumor strategy for GISTs.

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“…Several previous studies have demonstrated that dandelion extracts can induce apoptosis in some kinds of cancers, including breast cancer, prostate cancer (Sigstedt et al, 2008), hepatocarcinoma (Yoon et al, 2016), and cervical cancer. In this study, dandelion extracts suppressed the growth of BCSCs.…”

Section: Discussionmentioning

confidence: 99%

Taraxacum officinale dandelion extracts efficiently inhibited the breast cancer stem cell proliferation

Trinh¹,

Dang²,

Tran³

et al. 2016

Biomed Res Ther

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Abstract-Introduction:Breast cancer stem cells (BCSCs) play an important role in breast cancer initiation, metastasis, recurrence, and drug resistance. Therefore, targeting BCSCs is an essential strategy to suppress cancer growth. This study aimed to evaluate the effects of dandelion Taraxacum officinale extracts on BCSC proliferation in vitro in 2D and 3D cell culture platforms. Methods: The BCSCs were maintained understandard conditions, verified for expression of CD44 and CD24 surface markers, and transfected with GFP before use in experiments. In the 2D model, the BCSCs were cultured as adherent cells in standard culture plates; in the 3D model, the BCSCs were cultured on low-adherent plates to form spheroids. The effect of Dandelion extracts on proliferation of BCSC was assessed by evaluating induction of cell death, expression of genes of death receptor signaling pathways, and production of reactive oxygen species (ROS) by BCSCs. Results: BCSCs formed spheroids as microtumors in vitro and exhibited some in vivo characteristics of tumors, such as increased expression of N-cadherin and Slug, decreased expression of E-cadherin, capacity to invade into the extracellular matrix (ECM), and presence of a hypoxic environment at the core of tumor spheroids. The dandelion extracts significantly inhibited BCSC proliferation in both two-dimensional (2D) and three-dimensional (3D) models of BCSCs. However, the IC50 value of dandelion extracts in BCSCs in the 3D model was much higher than that in the 2D model. The results also demonstrated that BCSCs treated with Dandelion extracts showed increased expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor 2 (TRAILR2; i.e. death receptor 5;DR5). Moreover, treatment induced expression of DR4. Treatment with methanol dandelion extract enhanced production of ROS in BCSCs. Conclusion: Dandelion extracts are promising extracts for the treatment of breast tumors. The effect of methanol dandelion extract was better than that for ethanol extract. Importantly, BCSCs in 3D exhibited stronger drug resistance than those in 2D. In summary, our results indicate the strong potential of dandelion extracts as anti-cancer agents and rational use for drug development.

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Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells

Cited by 35 publications

References 27 publications

N-terminal gelsolin fragment potentiates TRAIL mediated death in resistant hepatoma cells

N-terminal gelsolin fragment potentiates TRAIL mediated death in resistant hepatoma cells

An inhibitor of the acetyltransferases CBP/p300 exerts antineoplastic effects on gastrointestinal stromal tumor cells

Taraxacum officinale dandelion extracts efficiently inhibited the breast cancer stem cell proliferation

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