scholarly journals 17α-Estradiol arrests cell cycle progression at G2/M and induces apoptotic cell death in human acute leukemia Jurkat T cells

2008 ◽  
Vol 231 (3) ◽  
pp. 401-412 ◽  
Author(s):  
D JUN ◽  
H PARK ◽  
J KIM ◽  
J KIM ◽  
W PARK ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cell Death ◽  
Acute Leukemia ◽  
Cell Cycle Progression ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Jurkat T Cells ◽  
Cycle Progression

scholarly journals Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chunfeng Xie ◽  
Xu Zhou ◽  
Chunhua Liang ◽  
Xiaoting Li ◽  
Miaomiao Ge ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
T Cells ◽  
Cell Death ◽  
Colony Formation ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Jurkat T Cells

Abstract Background Recently, a variety of clinical trials have shown that apatinib, a small-molecule anti-angiogenic drug, exerts promising inhibitory effects on multiple solid tumors, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism of apatinib on NSCLC remains unclear. Methods MTT, EdU, AO/EB staining, TUNEL staining, flow cytometry, colony formation assays were performed to investigate the effects of apatinib on cell proliferation, cell cycle distribution, apoptosis and cancer stem like properties. Wound healing and transwell assays were conducted to explore the role of apatinib on migration and invasion. The regulation of apatinib on VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling were detected. Furthermore, we collected conditioned medium (CM) from A549 and H1299 cells to stimulate phorbol myristate acetate (PMA)-activated THP-1 cells, and examined the effect of apatinib on PD-L1 expression in macrophages. The Jurkat T cells and NSCLC cells co-culture model was used to assess the effect of apatinib on T cells activation. Subcutaneous tumor formation models were established to evaluate the effects of apatinib in vivo. Histochemical, immunohistochemical staining and ELISA assay were used to examine the levels of signaling molecules in tumors. Results We showed that apatinib inhibited cell proliferation and promoted apoptosis in NSCLC cells in vitro. Apatinib induced cell cycle arrest at G1 phase and suppressed the expression of Cyclin D1 and CDK4. Moreover, apatinib upregulated Cleaved Caspase 3, Cleaved Caspase 9 and Bax, and downregulated Bcl-2 in NSCLC cells. The colony formation ability and the number of CD133 positive cells were significantly decreased by apatinib, suggesting that apatinib inhibited the malignant and stem-like features of NSCLC cells. Mechanistically, apatinib inhibited PD-L1 and c-Myc expression by targeting VEGFR2/STAT3 signaling. Apatinib also inhibited PD-L1 expression in THP-1 derived macrophages stimulated by CM from NSCLC cells. Furthermore, apatinib pretreatment increased CD69 expression and IFN-γ secretion in stimulated Jurkat T cells co-cultured with NSCLC cells. Apatinib also promoted ROS production and inhibited Nrf2 and p62 expression, leading to the autophagic and apoptotic cell death in NSCLC. Moreover, apatinib significantly inhibited tumor growth in vivo. Conclusion Our data indicated that apatinib induced autophagy and apoptosis in NSCLC via regulating VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling.

scholarly journals Antiproliferative activities of tricyclic amides derived from β-caryophyllene via the Ritter reaction against MDA-MB-231 breast cancer cells

2020 ◽  
Vol 11 (1) ◽  
pp. 118-124 ◽  
Author(s):  
XiXi Xu ◽  
Ariane Roseblade ◽  
Tristan Rawling ◽  
Alison T. Ung
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Apoptotic Cell ◽  
Ritter Reaction ◽  
Cycle Progression ◽  
The Ritter Reaction ◽  
Antiproliferative Activities

Tricyclic amides were successfully synthesised from β-caryophyllene via the Ritter reaction. Amides 3c and 6b inhibited proliferation of MDA-MB-231 cells. Compound 6b inhibited cell cycle progression and induced predominantly apoptotic cell death.

scholarly journals CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells.

1996 ◽  
Vol 183 (6) ◽  
pp. 2533-2540 ◽  
Author(s):  
M F Krummel ◽  
J P Allison
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Cycle Progression ◽  
Cell Activation ◽  
Apoptotic Cell ◽  
Activated T Cells ◽  
Activated State

While interactions between CD28 and members of the B7 family costimulate and enhance T cell responses, recent evidence indicates that the CD28 homologue CTLA-4 plays a downregulatory role. The mechanism by which this occurs is not clear, but it has been suggested that CTLA-4 terminates ongoing responses of activated T cells, perhaps by induction of apoptosis. Here we demonstrate that CTLA-4 engagement by antibody cross-linking or binding to B7 inhibits proliferation and accumulation of the primary T cell growth factor, IL-2, by cells stimulated with anti-CD3 and anti-CD28. This inhibition is not a result of enhanced cell death. Rather it appears to result from restriction of transition from the G1 to the S phase of the cell cycle. Our observation that upregulation of both the IL-2R alpha chain and the CD69 activation antigen are inhibited by CTLA-4 engagement supplies further evidence that CTLA-4 restricts the progression of T cells to an activated state. Together this data demonstrates that CTLA-4 can regulate T cell activation in the absence of induction of apoptotic cell death.

scholarly journals Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis.

1994 ◽  
Vol 14 (12) ◽  
pp. 8166-8173 ◽  
Author(s):  
B Shan ◽  
W H Lee
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Progression ◽  
Apoptotic Cell ◽  
Expression System ◽  
Critical Role ◽  
S Phase ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Phase Entry

E2F-1, the first gene product identified among a family of E2F transcription factors, is thought to play a critical role in G1/S progression of the cell cycle. Transcriptional activities of E2F are modulated during the cell cycle, mainly by the formation of complexes between E2F and several key regulators of cell cycle such as the retinoblastoma protein and related proteins. To further understand the roles of E2F in the cell cycle progression, we have overexpressed exogenous E2F-1 by using a tetracycline-controlled expression system. We have found that the induced expression of E2F-1 in Rat-2 fibroblasts promotes S-phase entry and subsequently leads to apoptosis. The apoptosis occurs in an E2F-1 dose-dependent manner. Cells resistant to the induction of apoptosis have lost the ability to express exogenous E2F-1. Cells growing in low serum are more sensitive to the E2F-1-mediated cell death. Overexpression of E2F-1 mutants that impair DNA binding or transactivation does not alter cell cycle progression or induce apoptosis. These results define a novel pathway to apoptosis and demonstrate that premature S-phase entry is associated with apoptotic cell death.

scholarly journals Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis

1994 ◽  
Vol 14 (12) ◽  
pp. 8166-8173 ◽  
Author(s):  
B Shan ◽  
W H Lee
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Progression ◽  
Apoptotic Cell ◽  
Expression System ◽  
Critical Role ◽  
S Phase ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Phase Entry

E2F-1, the first gene product identified among a family of E2F transcription factors, is thought to play a critical role in G1/S progression of the cell cycle. Transcriptional activities of E2F are modulated during the cell cycle, mainly by the formation of complexes between E2F and several key regulators of cell cycle such as the retinoblastoma protein and related proteins. To further understand the roles of E2F in the cell cycle progression, we have overexpressed exogenous E2F-1 by using a tetracycline-controlled expression system. We have found that the induced expression of E2F-1 in Rat-2 fibroblasts promotes S-phase entry and subsequently leads to apoptosis. The apoptosis occurs in an E2F-1 dose-dependent manner. Cells resistant to the induction of apoptosis have lost the ability to express exogenous E2F-1. Cells growing in low serum are more sensitive to the E2F-1-mediated cell death. Overexpression of E2F-1 mutants that impair DNA binding or transactivation does not alter cell cycle progression or induce apoptosis. These results define a novel pathway to apoptosis and demonstrate that premature S-phase entry is associated with apoptotic cell death.

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