Low-Dose Hyper-radiosensitivity: A Consequence of Ineffective Cell Cycle Arrest of Radiation-Damaged G2-Phase Cells

2004 ◽  
Vol 161 (3) ◽  
pp. 247-255 ◽  
Author(s):  
B. Marples ◽  
B. G. Wouters ◽  
S. J. Collis ◽  
A. J. Chalmers ◽  
M. C. Joiner
ACS Nano ◽  
2013 ◽  
Vol 7 (11) ◽  
pp. 10433-10433 ◽  
Author(s):  
Jong Ah Kim ◽  
Christoffer Åberg ◽  
Guillermo de Cárcer ◽  
Marcos Malumbres ◽  
Anna Salvati ◽  
...  

Author(s):  
Nguyen Thi Bich Loan ◽  
Nguyen Lai Thanh ◽  
Pierre Duez ◽  
Nguyen Dinh Thang

Extracts from Croton kongenis present anticancer activities on various cancers. However, there is no research conducted to investigate the effects of Croton kongenis extracts on cervical cancer as well as on zebrafish. In this study, we demonstrated that Croton kongenis ethanol extract expressed high toxicity to cervical cancer Hela cells with an IC50 dose of 20.4 µg/mL and to zebrafish embryos with malformations, lethality and hatching inhibition at 72-hpf at effective dose of 125 µg/mL. Interestingly, treatment with Croton kongenis ethanol extract caused cell-cycle-arrest at the G2 phase. Particularly, percentages of Croton kongenis ethanol extract-treated cells in G1, S, G2/M were 70%, 6% and 23%, while percentages of control cells in G1, S, G2/M were 65%, 15% and 18%, respectively. Consistent with cell-cycle-arrest, the expressions of CDKN1A, CDNK2A and p53 in Croton kongenis ethanol extract-treated cells were up-regulated 2.0-, 1.65- and 1.8-fold, respectively. Significantly, treatment with Croton kongenis ethanol extract inhibited anchorage-independent growth of Hela cells; the number of colonies formed in soft-agar of Croton kongenis ethanol extract-treated cells was only one-fourth of that of control cells. In conclusion, we suggest that Croton kongenis ethanol extract could be able to use as a traditional medicine for treatment of cervical cancer.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1537-1537 ◽  
Author(s):  
C. Kurkjian ◽  
N. B. Janakiram ◽  
S. Guruswamy ◽  
C. V. Rao ◽  
H. Ozer

1537 Background: Clinical and preclinical studies suggest that cyclooxygenase (COX)-2 inhibitors reduce the risk of various cancers, however, their administration is associated with an increased cardiovascular risk. Agents with 5-LOX/COX inhibition provide a possible approach for improving chemopreventive efficacy without unwanted side effects. COX and LOX inhibition have also been associated with an increase in PPAR γ expression. The present experiments tested the effects of licofelone (L) in breast cancer cell lines and assessed whether dual inhibition of LOX and COX may potentiate the action of rosiglitazone (R). Methods: MDA-MB-231 and MCF-7 cells were exposed to sub-toxic concentrations of L and R alone and in combination and analyzed for growth inhibition (MTT method), apoptosis (EB-AO and DAPI methods), cell-cycle analysis (flow cytometry), and protein expression (immunoblot method). Results: L and R inhibited cell growth in a dose-dependent manner in both cell lines. Combination therapy resulted in significant rates of apoptosis, particularly at high doses in both cell lines (p<0.001). Flow cytometric analysis showed that L and R exhibited cell cycle arrest at the G0/G1 phase in MDA-MB-231 cells. The low dose combination did not promote cell cycle arrest while the higher dose combination therapy demonstrated significant inhibition (p <0.0009). In MCF-7 cells, G0/G1 phase blockade was noted in L and R treated cells as well as in the low dose simultaneous combination therapy. Intermediate and high dose combination therapy exhibited increased cell cycle arrest at G0/G1 when L was administered 12 hours before R (p = 0.0030 and 0.0017). Western blot analysis showed increased expression of p21WAFI/CIPI and decreased cyclin D1 expression in both cell lines after therapy. Both agents induced caspase-3 expression in MDA-MB-231 cells at high concentrations, with even higher expression observed in the combination treatment. MCF-7 cells demonstrated PARP cleavage at all doses when compared to control. Conclusions: Our results suggest that L is a potential agent for prevention and treatment of breast cancer and the combination of low doses of L and R provide further promise in improving efficacy against breast cancer. No significant financial relationships to disclose.


2009 ◽  
Vol 20 (24) ◽  
pp. 5064-5073 ◽  
Author(s):  
Li-Fang Shyu ◽  
Jianjun Sun ◽  
Hui-Min Chung ◽  
Yi-Chun Huang ◽  
Wu-Min Deng

Temporal and spatial regulation of cell division is critical for proper development of multicellular organisms. An important aspect of this regulation is cell-cycle arrest, which in many cell types is coupled with differentiated status. Here we report that the polar cells—a group of follicle cells differentiated early during Drosophila oogenesis—are arrested at G2 phase and can serve as a model cell type for investigation of developmental regulation of cell-cycle arrest. On examining the effects of String, a mitosis-promoting phosphatase Cdc25 homolog, and Notch signaling in polar cells, we found that misexpression of String can trigger mitosis in existing polar cells to induce extra polar cells. Normally, differentiation of the polar cells requires Notch signaling. We found that the Notch-induced extra polar cells arise through recruitment of the neighboring cells rather than promotion of proliferation, and they are also arrested at G2 phase. Notch signaling is probably involved in down-regulating String in polar cells, thus inducing the G2 cell-cycle arrest.


Oncogene ◽  
2003 ◽  
Vol 22 (14) ◽  
pp. 2110-2120 ◽  
Author(s):  
Annapaola Franchitto ◽  
Pietro Pichierri ◽  
Rita Piergentili ◽  
Marco Crescenzi ◽  
Margherita Bignami ◽  
...  

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