Reversine stimulates adipocyte differentiation and downregulates Akt and p70s6k signaling pathways in 3T3-L1 cells

Kim, Yong Kee; Choi, Hyeyoung; Kim, Nam Hyun; Lee, Woojung; Seo, Dong Wan; Kang, Dong Won; Lee, Hoi Young; Han, Jeung‐Whan; Sw, Park; Kim, Su‐Nam

doi:10.1016/j.bbrc.2007.04.165

Cited by 53 publications

(43 citation statements)

References 26 publications

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“…Recently, it has been shown that reversine enhances adipocyte differentiation by inducing the expression of adipogenic marker genes (22). In addition, human fibroblasts treated with reversine are able to differentiate in muscle cells both in vitro and in vivo (2).…”

Section: Discussionmentioning

confidence: 99%

Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells

D’Alise

Amabile

Iovino

et al. 2008

Molecular Cancer Therapeutics

116

107

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The demonstration that the small synthetic molecule reversine [2-(4-morpholinoanilino)-N 6 -cyclohexyladenine] promotes the dedifferentiation of committed cells into multipotent progenitor-type cells has raised hopes on the exploitation of this small chemical tool for the generation of stem cells. Here, we show that reversine causes a failure in cytokinesis and induces polyploidization. These effects of reversine are due to the inhibition of Aurora A and B, two related kinases that are implicated in several aspects of mitosis and that are frequently amplified and overexpressed in human tumors. Reversine inhibits the phosphorylation of histone H3, a direct downstream target of Aurora kinases. Similarly to the Aurora kinase inhibitor VX-680, which has recently entered phase II clinical trials for cancer treatment, reversine inhibited colony formation of leukemic cells from patients with acute myeloid leukemia but was significantly less toxic than VX-680 on cells from healthy donors. The crystal structure of the reversine-Aurora B kinase complex shows that reversine is a novel class of ATP-competitive Aurora kinase inhibitors. Thus, although our studies raise serious doubts on the application of reversine in regenerative medicine, they support the paradigm that reversine might be a useful agent in cancer chemotherapy. [Mol Cancer Ther 2008;7(5):1140 -9]

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Section: Discussionmentioning

confidence: 99%

Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells

D’Alise

Amabile

Iovino

et al. 2008

Molecular Cancer Therapeutics

116

107

View full text Add to dashboard Cite

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“…Later, some reports showed that reversine had a role in regeneration (Anastasia et al 2006;Kim et al 2007;Saraiya et al 2010;Anastasia et al 2010;Jung and Williams 2011). Moreover, a recent report showed that reversine had anti-tumor capabilities such as for a myeloma cell line (McMillin et al 2010), and demonstrated that reversine could suppress the expression of cell cycle related proteins Aurora kinase A (Aur-A) and Aurora kinase B (Aur-B), and also could suppress enzymes involved in cell growth signaling, such as JAK2 and SRC (McMillin et al 2010;Hua et al 2012;Shan et al 2007;Jemaà et al 2012;Kuo et al 2012;Hsieh et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Synergistic antitumor activity of reversine combined with aspirin in cervical carcinoma in vitro and in vivo

et al. 2013

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A recent report showed that reversine treatment could induce murine myoblasts dedifferentiation into multipotent progenitor cells and inhibit proliferation of some tumors, and other reports showed that apoptosis of lung adenocarcinoma cells could be induced by aspirin. The aim of the present study was to evaluate the synergistic antitumor effects of reversine and aspirin on cervical cancer. The inhibition rate of reversine and aspirin on cervical cancer cell lines' (HeLa and U14) was determined by MTT method, cell cycle of HeLa and U14 cells was analyzed by FACS, mitochondrial membrane potential of HeLa and U14 was detected using a JC-1 kit. HeLa and U14 colony formation was analyzed by soft agar colony formation assay. The expression of caspase-3, Bcl-2/Bax, cyclin D1 and p21 was detected by qRT-PCR and Western Blotting. Moreover, tumor weight and tumor volume was assessed using a murine model of cervical cancer with U14 cells subcutaneously (s.c.) administered into the neck, separately or combined with drug administration via the intraperitoneal (i.p.) route. The inhibition rate of cells in the combination group (10 lmol/L reversine, 10 mmol/ L aspirin) increased significantly in comparison to that when the drugs were used alone (P \ 0.05); moreover, this combination could synergistically inhibit the proliferation of five cervical cancer cell lines (HeLa, U14, Siha, Caski and C33A). In the therapeutic mouse model, tumor weight and tumor volume of cervical cancer bearing mice was more reduced when compared with the control agents (P \ 0.05) in tumor-bearing mice. The combination of reversine and aspirin exerts synergistic growth inhibition and apoptosis induction on cervical cancers cells.

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“…[2][3][4][5] Adiponectin is expressed by small adipocytes, and improves insulin sensitivity. 6,7) Therefore, an increased number of small adipocytes is important for maintaining metabolic homeostasis.…”

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confidence: 99%

Polymethoxyflavonoids from <i>Kaempferia parviflora</i> Induce Adipogenesis on 3T3-L1 Preadipocytes by Regulating Transcription Factors at an Early Stage of Differentiation

Horikawa

Shimada

Okabe

et al. 2012

Biological & Pharmaceutical Bulletin

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We previously reported that Kaempferia parviflora WALL. ex BAKER (KP) and its ethyl acetate extract (KPE) improve various metabolic disorders in obesity-model mice. However the mechanism is not certain, and, in this study, in order to elucidate the mechanism of the suppressive effect of KP on fat accumulation, we focused on adipocytes, which are closely linked to metabolic diseases. The finding was that KPE and its components, 3,5,7,4′-tetramethoxyflavone and 3,5,7,3′,4′-pentamethoxyflavone, strongly induced differentiation of 3T3-L1 preadipocytes to adipocytes. The above two polymethoxyflavonoids (PMFs) also induced adiponectin mRNA levels, and release of adiponectin into the medium. In addition, these PMFs enhanced the expression of peroxisome proliferator-activated receptor γ (PPARγ), but did not show PPARγ ligand activity. We then investigated the expression of the differentiation-regulator located upstream of PPARγ. Expression of CCAAT/enhancer-binding protein (C/EBP) β and -δ mRNA, a transcriptional regulator of PPARγ, was induced, and expression of GATA-2 mRNA, a down-regulator of adipogenesis, was suppressed by these PMFs. These functions of the KP PMFs that enhance adipogenesis and secretion of adiponectin are, to some extent at least, involved in the mechanisms of anti-metabolic disorders effects.

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Reversine stimulates adipocyte differentiation and downregulates Akt and p70s6k signaling pathways in 3T3-L1 cells

Cited by 53 publications

References 26 publications

Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells

Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells

Synergistic antitumor activity of reversine combined with aspirin in cervical carcinoma in vitro and in vivo

Polymethoxyflavonoids from <i>Kaempferia parviflora</i> Induce Adipogenesis on 3T3-L1 Preadipocytes by Regulating Transcription Factors at an Early Stage of Differentiation

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