Deoxypodophyllotoxin Induces G2/M Cell Cycle Arrest and Apoptosis in SGC-7901 Cells and Inhibits Tumor Growth in Vivo

We have demonstrated for the first time that the steroid metabolite, 2-methoxyestradiol (2-ME) is a powerful growth inhibitor of human osteosarcoma 143 B cell line by pleiotropic mechanisms involving cell cycle arrest at two different points and apoptosis. The ability of 2-ME to inhibit cell cycle at the respective points has been found concentration dependent. 1 microM 2-ME inhibited cell cycle at G1 phase while 10 microM 2-ME caused G2/M cell cycle arrest. As a natural estrogen metabolite 2-ME is expected to perturb the stability of microtubules (MT) in vivo analogously to Taxol--the MT binding anticancer agent. Contrary to 2-ME, Taxol induced accumulation of osteosarcoma cells in G2/M phase of cell cycle only. The presented data strongly suggest two different mechanisms of cytotoxic action of 2-ME at the level of a single cell.

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Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk

The American Journal of Chinese Medicine ◽

10.1142/s0192415x15500469 ◽

2015 ◽

Vol 43 (04) ◽

pp. 743-756 ◽

Cited By ~ 25

Author(s):

Lian-Wen Qi ◽

Zhiyu Zhang ◽

Chun-Feng Zhang ◽

Samantha Anderson ◽

Qun Liu ◽

...

Keyword(s):

Cell Cycle ◽

Colon Cancer ◽

Cell Cycle Arrest ◽

Strong Support ◽

Cancer Chemoprevention ◽

M Cell ◽

Cycle Arrest ◽

Hct 116 ◽

Hct 116 Cells

Chemopreventive agents can be identified from botanicals. Recently, there has been strong support for the potential of 6-shogaol, a natural compound from dietary ginger (Zingiber officinale), in cancer chemoprevention. However, whether 6-shogaol inhibits the growth of colorectal tumors in vivo remains unknown, and the underlying anticancer mechanisms have not been well characterized. In this work, we observed that 6-shogaol (15 mg/kg) significantly inhibited colorectal tumor growth in a xenograft mouse model. We show that 6-shogaol inhibited HCT-116 and SW-480 cell proliferation with IC50 of 7.5 and 10 μM, respectively. Growth of HCT-116 cells was arrested at the G2/M phase of the cell cycle, primarily mediated by the up-regulation of p53, the CDK inhibitor p21waf1/cip1 and GADD45α, and by the down-regulation of cdc2 and cdc25A. Using p53-/- and p53+/+ HCT-116 cells, we confirmed that p53/p21 was the main pathway that contributed to the G2/M cell cycle arrest by 6-shogaol. 6-Shogaol induced apoptosis, mainly through the mitochondrial pathway, and the bcl-2 family might act as a key regulator. Our results demonstrated that 6-shogaol induces cancer cell death by inducing G2/M cell cycle arrest and apoptosis. 6-Shogaol could be an active natural product in colon cancer chemoprevention.

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Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest

10.1101/825752 ◽

2019 ◽

Author(s):

Sara Marelli ◽

James C Williamson ◽

Anna V Protasio ◽

Adi Naamati ◽

Edward JD Greenwood ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Cycle Progression ◽

M Cell ◽

Regulatory Subunits ◽

Cycle Arrest ◽

Identify Amino Acid ◽

Necessary And Sufficient ◽

Hiv 1

AbstractThe seminal description of cellular restriction factor APOBEC3G and its antagonism by HIV-1 Vif has underpinned two decades of research on the host-virus interaction. As well as APOBEC3G and its homologues, however, we have recently discovered that Vif is also able to degrade the PPP2R5 family of regulatory subunits of key cellular phosphatase PP2A (PPP2R5A-E) (Greenwood et al., 2016; Naamati et al., 2019). We now identify amino acid polymorphisms at positions 31 and 128 of HIV-1 Vif which selectively regulate the degradation of PPP2R5 family proteins. These residues covary across HIV-1 viruses in vivo, favouring depletion of PPP2R5A-E. Through analysis of point mutants and naturally occurring Vif variants, we further show that degradation of PPP2R5 family subunits is both necessary and sufficient for Vif-dependent G2/M cell cycle arrest. Antagonism of PP2A by HIV-1 Vif is therefore independent of APOBEC3 family proteins, and regulates cell cycle progression in HIV-infected cells.

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Effect of Marsdenia tenacissima extract on G2/M cell cycle arrest by upregulating 14-3-3σ and downregulating c-myc in vitro and in vivo

Chinese Herbal Medicines ◽

10.1016/j.chmed.2019.03.002 ◽

2019 ◽

Vol 11 (2) ◽

pp. 169-176 ◽

Cited By ~ 1

Author(s):

Li Sun ◽

Qurat UI Ain ◽

Ying-sheng Gao ◽

Ghulam Jilany Khan ◽

Sheng-tao Yuan ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

M Cell ◽

Cycle Arrest ◽

Marsdenia Tenacissima

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The Zn(S-pr-thiosal)2 complex attenuates murine breast cancer growth by inducing apoptosis and G1/S cell cycle arrest

Future Medicinal Chemistry ◽

10.4155/fmc-2019-0215 ◽

2020 ◽

Vol 12 (10) ◽

pp. 897-914

Author(s):

Sasa Benazic ◽

Zana Besser Silconi ◽

Andra Jevtovic ◽

Milena Jurisevic ◽

Jelena Milovanovic ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Tumor Growth ◽

Cell Cycle Arrest ◽

Cell Cycle Progression ◽

Cyclin D3 ◽

Antitumor Effects ◽

Cycle Arrest ◽

4T1 Cells

Aim: We investigated the antitumor effects of zinc(II) complex with S-propyl thiosalicylic acid [Zn( S-pr-thiosal)2] in 4T1 murine breast cancer model. Results: The Zn( S-pr-thiosal)2 complex reduced primary tumor growth in vivo and induced tumor cell apoptosis. The Zn( S-pr-thiosal)2 complex disrupted the balance between pro- and antiapoptotic Bcl-2 family members in 4T1 cells and induced G1/S cell cycle arrest. The Zn( S-pr-thiosal)2 complex increased the percentage of p16, p21 and p27 positive 4T1 cells. There was a significantly decrease in expression of STAT3 and its targets c-Myc and cyclin D3 in 4T1 cells treated with the Zn( S-pr-thiosal)2 complex thus contributing to G1/S cell cycle arrest and/or apoptosis. Conclusion: Our data suggest that the Zn( S-pr-thiosal)2 complex restricted tumor growth through induction of mitochondrial-driven apoptosis and suppression of cell cycle progression.

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Romidepsin Induces G2/M Phase Arrest and Apoptosis in Cholangiocarcinoma Cells

Technology in Cancer Research & Treatment ◽

10.1177/1533033820960754 ◽

2020 ◽

Vol 19 ◽

pp. 153303382096075

Author(s):

Pihong Li ◽

Luguang Liu ◽

Xiangguo Dang ◽

Xingsong Tian

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Antitumor Effect ◽

Caspase 3 ◽

M Cell ◽

Cycle Arrest ◽

Phase Arrest ◽

M Phase

Background: Cholangiocarcinoma (CCA) is an extremely intractable malignancy since most patients are already in an advanced stage when firstly discovered. CCA needs more effective treatment, especially for advanced cases. Our study aimed to evaluate the effect of romidepsin on CCA cells in vitro and in vivo and explore the underlying mechanisms. Methods: The antitumor effect was determined by cell viability, cell cycle and apoptosis assays. A CCK-8 assay was performed to measure the cytotoxicity of romidepsin on CCA cells, and flow cytometry was used to evaluate the effects of romidepsin on the cell cycle and apoptosis. Moreover, the in vivo effects of romidepsin were measured in a CCA xenograft model. Results: Romidepsin could reduce the viability of CCA cells and induce G2/M cell cycle arrest and apoptosis, indicating that romidepsin has a significant antitumor effect on CCA cells in vitro. Mechanistically, the antitumor effect of romidepsin on the CCA cell lines was mediated by the induction of G2/M cell cycle arrest and promotion of cell apoptosis. The G2/M phase arrest of the CCA cells was associated with the downregulation of cyclinB and upregulation of the p-cdc2 protein, resulting in cell cycle arrest. The apoptosis of the CCA cells induced by romidepsin was attributed to the activation of caspase-3. Furthermore, romidepsin significantly inhibited the growth of the tumor volume of the CCLP-1 xenograft, indicating that romidepsin significantly inhibited the proliferation of CCA cells in vivo. Conclusions: Romidepsin suppressed the proliferation of CCA cells by inducing cell cycle arrest through cdc2/cyclinB and cell apoptosis by targeting caspase-3/PARP both in vitro and in vivo, indicating that romidepsin is a potential therapeutic agent for CCA.

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A small molecule based on the pRb2/p130 spacer domain leads to inhibition of cdk2 activity, cell cycle arrest and tumor growth reduction in vivo

Oncogene ◽

10.1038/sj.onc.1209987 ◽

2006 ◽

Vol 26 (13) ◽

pp. 1829-1839 ◽

Cited By ~ 26

Author(s):

L Bagella ◽

A Sun ◽

T Tonini ◽

G Abbadessa ◽

G Cottone ◽

...

Keyword(s):

Cell Cycle ◽

Tumor Growth ◽

Cell Cycle Arrest ◽

Small Molecule ◽

Growth Reduction ◽

Cycle Arrest ◽

Cdk2 Activity

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Sulforaphane induces cell cycle arrest and apoptosis in murine osteosarcoma cells in vitro and inhibits tumor growth in vivo

Oncology Reports ◽

10.3892/or.18.5.1263 ◽

2007 ◽

Cited By ~ 4

Author(s):

Taka-aki Matsui ◽

Hiroaki Murata ◽

Tomoya Sakabe ◽

Yoshihiro Sowa ◽

Naoyuki Horie ◽

...

Keyword(s):

Cell Cycle ◽

Tumor Growth ◽

Cell Cycle Arrest ◽

Osteosarcoma Cells ◽

Cycle Arrest ◽

Murine Osteosarcoma

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The therapeutic effectiveness of 177Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2/M cell cycle arrest

Leukemia ◽

10.1038/s41375-019-0677-4 ◽

2019 ◽

Vol 34 (5) ◽

pp. 1315-1328 ◽

Cited By ~ 2

Author(s):

Alexandre Pichard ◽

Sara Marcatili ◽

Jihad Karam ◽

Julie Constanzo ◽

Riad Ladjohounlou ◽

...

Keyword(s):

Cell Cycle ◽

Tumor Growth ◽

B Cell ◽

Cell Cycle Arrest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Growth Delay ◽

M Cell ◽

Cycle Arrest

AbstractSome patients with B-cell non-Hodkin lymphoma Lymphoma (NHL) become refractory to rituximab (anti-CD20 antibody) therapy associated with chemotherapy. Here, the effect of the anti-CD37 antibody-radionuclide conjugate lutetium-177 (177Lu)-lilotomab (Betalutin®) was investigated in preclinical models of NHL. In SCID mice bearing DOHH2 (transformed follicular lymphoma, FL) cell xenografts, 177Lu-lilotomab significantly delayed tumor growth, even at low activity (100 MBq/kg). In athymic mice bearing OCI-Ly8 (diffuse large B-cell lymphoma, DLBCL) or Ramos (Burkitt’s lymphoma) cell xenografts, 177Lu-lilotomab activity had to be increased to 500 MBq/kg to show a significant tumor growth delay. Clonogenic and proliferation assays showed that DOHH2 cells were highly sensitive to 177Lu-lilotomab, while Ramos cells were the least sensitive, and U2932 (DLBCL), OCI-Ly8, and Rec-1 (mantle cell lymphoma) cells displayed intermediate sensitivity. The strong 177Lu-lilotomab cytotoxicity observed in DOHH2 cells correlated with reduced G2/M cell cycle arrest, lower WEE-1- and MYT-1-mediated phosphorylation of cyclin-dependent kinase-1 (CDK1), and higher apoptosis. In agreement, 177Lu-lilotomab efficacy in vitro, in vivo, and in patient samples was increased when combined with G2/M cell cycle arrest inhibitors (MK-1775 and PD-166285). These results indicate that 177Lu-lilotomab is particularly efficient in treating tumors with reduced inhibitory CDK1 phosphorylation, such as transformed FL.

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