Reversine, a 2,6-disubstituted Purine, as an Anti-cancer Agent in Differentiated and Undifferentiated Thyroid Cancer Cells

Hua, Shih-Che; Chang, Tien–Chun; Chen, Hau-Ren; Lu, Chieh-Hsiang; Liu, Yiwen; Chen, Shu-Hsin; Yu, Hui-I; Chang, Yi‐Ping; Lee, Ying‐Ray

doi:10.1007/s11095-012-0727-3

Cited by 42 publications

(47 citation statements)

References 26 publications

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“…In the present study, reversine, a substituted purine, could induce fibroblasts transformation or dedifferentiation through protein kinases (such as JAK2, SRC, and Akt) and modulation of phosphorylation (Hua et al 2012;Shan et al 2007;. Later on, research showed that it exhibited a significant antitumor activity against human cancer cells characterized by virtually uncontrolled tumour growth and spread of abnormal cells (Jemaà et al 2012;Kuo et al 2012;Hsieh et al 2007).…”

Section: Discussionmentioning

confidence: 74%

“…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). However, the definite molecular signaling pathway of the anti-tumor effects of reversine has not yet been understood.…”

Section: Introductionmentioning

confidence: 99%

“…Reversine Reversine is a low cost and non-chemotherapeutic alternative drug for oral squamous cell carcinoma and breast cancer treatment (McMillin et al 2010;Hua et al 2012;Shan et al 2007;Jemaà et al 2012;Kuo et al 2012;Hsieh et al 2007). However, it is still unknown, whether reversine and aspirin could induce apoptosis in cervical cancer cell.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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“…35,[41][42][43][44][45] These findings indicate that reversine exerts relatively broad anticancer effects. Here, we show that low-dose reversine, 0.5 μM, a concentration at which reversine selectively inhibits MPS1, fails to preferentially kill TP53 -/-HCT 116 colon carcinoma cells.…”

Section: Discussionmentioning

confidence: 93%

Preferential killing of p53-deficient cancer cells by reversine

et al. 2012

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“…Reversine has been shown to inhibit cell proliferation [18, 22], to induce cell-cycle arrest at the G2/M phase [1, 3, 22-24], to trigger apoptosis [3, 5, 10, 23-27], to induce cell swelling with polyploidy [1, 9, 23, 27], and to stimulate autophagy [3, 10, 24]. …”

Section: Introductionmentioning

confidence: 99%

Inhibition of Suicidal Erythrocyte Death by Reversine

Jèmaà

Fezai

Läng³

2017

Cell Physiol Biochem

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Background/Aims: The A3 adenosine receptor antagonist reversine (2-(4-morpholinoanilino)-6-cyclohexylaminopurine) influences cellular differentiation, inhibits cell proliferation, induces cell-cycle arrest, triggers apoptosis, causes cell swelling with polyploidy and stimulates autophagy. The effect on apoptosis involves mitochondria and caspases. Erythrocytes are lacking mitochondria but express caspases and are, similar to apoptosis of nucleated cells, able to enter suicidal erythrocyte death or eryptosis. Stimulators of eryptosis include increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), energy depletion and oxidative stress. The present study explored, whether reversine influences eryptosis. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding and cell volume from forward scatter. Measurements were made without or with energy depletion (glucose deprivation for 48 hours), Ca²⁺ loading (30 minutes treatment with 1 µM Ca²⁺ ionophore ionomycin), or oxidative stress (15 min exposure to 0.3 mM tert-butylhydroperoxide). Results: A 48 hours exposure of human erythrocytes to reversine (1-10 µM) did not significantly modify the percentage of annexin-V-binding cells and forward scatter. Energy depletion, Ca²⁺ loading, and oxidative stress were each followed by profound and significant increase of the percentage annexin-V-binding erythrocytes and a significant decrease of forward scatter. The effects of each, Ca²⁺ loading, energy depletion and oxidative stress on annexin-V-binding were significantly blunted in the presence of reversine (1-10 µM). The effect of ionomycin, but not the effects of energy depletion and oxidative stress on forward scatter were again significantly blunted in the presence of reversine (≥1 µM]. Conclusions: Reversine is a powerful inhibitor of cell membrane scrambling following energy depletion, Ca²⁺ loading and oxidative stress.

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Reversine, a 2,6-disubstituted Purine, as an Anti-cancer Agent in Differentiated and Undifferentiated Thyroid Cancer Cells

Cited by 42 publications

References 26 publications

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

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

Preferential killing of p53-deficient cancer cells by reversine

Inhibition of Suicidal Erythrocyte Death by Reversine

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