Growth Inhibition of Uterine Cervical Cancer Cells by a Sequential Administration of Anticancer Drugs and Irradiation

ABT-737, a B cell lymphoma-2 (Bcl-2) family inhibitor, activates apoptosis in cancer cells. Arsenic trioxide is an apoptosis activator that impairs cancer cell survival. The aim of this study was to evaluate the effect of a combination treatment with ABT-737 and arsenic trioxide on uterine cervical cancer cells. MTT (3-(4,5-dimethylthiazol-2-yl)-25-diphenyltetrazolium bromide) assay revealed that ABT-737 and arsenic trioxide induced a synergistic effect on uterine cervical cancer cells. Arsenic trioxide enhanced ABT-737-induced apoptosis and caspase-7 activation and the ABT-737-mediated reduction of anti-apoptotic protein Mcl-1 in Caski cells. Western blot assay revealed that arsenic trioxide promoted the ABT-737-mediated reduction of CDK6 and thymidylate synthetase in Caski cells. Arsenic trioxide promoted ABT-737-inhibited mitochondrial membrane potential and ABT-737-inhibited ANT expression in Caski cells. However, ABT-737-elicited reactive oxygen species were not enhanced by arsenic trioxide. The combined treatment induced an anti-apoptosis autophagy in SiHa cells. This study is the first to demonstrate that a combination treatment with ABT-737 and arsenic trioxide induces a synergistic effect on uterine cervical cancer cells through apoptosis. Our findings provide new insights into uterine cervical cancer treatment.

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Histone deacetylase inhibitor BML-210 induces growth inhibition and apoptosis and regulates HDAC and DAPC complex expression levels in cervical cancer cells

Molecular Biology Reports ◽

10.1007/s11033-012-1892-5 ◽

2012 ◽

Vol 39 (12) ◽

pp. 10179-10186 ◽

Cited By ~ 5

Author(s):

Veronika V. Borutinskaite ◽

Karl-Eric Magnusson ◽

Ruta Navakauskiene

Keyword(s):

Cervical Cancer ◽

Growth Inhibition ◽

Cancer Cells ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Expression Levels ◽

Deacetylase Inhibitor ◽

Cervical Cancer Cells ◽

Complex Expression

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Down-regulation of phospho-non-receptor Src tyrosine kinases contributes to growth inhibition of cervical cancer cells

Medical Oncology ◽

10.1007/s12032-010-9583-3 ◽

2010 ◽

Vol 28 (4) ◽

pp. 1495-1506 ◽

Cited By ~ 9

Author(s):

Lu Kong ◽

Zhihong Deng ◽

Yanzhong Zhao ◽

Yamei Wang ◽

Fazlul H. Sarkar ◽

...

Keyword(s):

Cervical Cancer ◽

Growth Inhibition ◽

Cancer Cells ◽

Tyrosine Kinases ◽

Down Regulation ◽

Src Tyrosine Kinases ◽

Cervical Cancer Cells

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Effects of ABT‑737 combined with irradiation treatment on uterine cervical cancer cells

Oncology Letters ◽

10.3892/ol.2019.10755 ◽

2019 ◽

Cited By ~ 1

Author(s):

Huang‑Pin Shen ◽

Wen‑Jun Wu ◽

Jiunn‑Liang Ko ◽

Tzu‑Fan Wu ◽

Shun‑Fa Yang ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Uterine Cervical Cancer ◽

Irradiation Treatment ◽

Cervical Cancer Cells

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Disruption of HPV16-E7 by CRISPR/Cas System Induces Apoptosis and Growth Inhibition in HPV16 Positive Human Cervical Cancer Cells

BioMed Research International ◽

10.1155/2014/612823 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 57

Author(s):

Zheng Hu ◽

Lan Yu ◽

Da Zhu ◽

Wencheng Ding ◽

Xiaoli Wang ◽

...

Keyword(s):

Cervical Cancer ◽

Growth Inhibition ◽

Cancer Cells ◽

Hpv Infection ◽

Hek293 Cells ◽

Guide Rna ◽

System A ◽

Cervical Cancer Cells ◽

E6 And E7 ◽

Human Cervical Cancer Cells

High-risk human papillomavirus (HR-HPV) has been recognized as a major causative agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervical cancer cells. By using clustered regularly interspaced short palindromic repeats- (CRISPR-) associated protein system (CRISPR/Cas system), a widely used genome editing tool in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed for the first time that the HPV16-E7 single-guide RNA (sgRNA) guided CRISPR/Cas system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to downregulation of E7 protein and upregulation of tumor suppressor protein pRb. Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might be used as a therapeutic strategy for the treatment of cervical cancer.

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Notch1 induces cell cycle arrest and apoptosis in human cervical cancer cells: involvement of nuclear factor kappa B inhibition

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2007.00872.x ◽

2007 ◽

Vol 17 (2) ◽

pp. 502-510 ◽

Cited By ~ 25

Author(s):

J. Yao ◽

L. Duan ◽

M. Fan ◽

J. Yuan ◽

X. Wu

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Growth Inhibition ◽

Cancer Cells ◽

Nuclear Factor Kappa B ◽

Nuclear Factor ◽

Cycle Arrest ◽

Cervical Cancer Cells ◽

Human Cervical Cancer Cells ◽

Human Cervical Cancer

Notch signaling can serve as a tumor suppressor or tumor promoter in the same kind of cancer, such as human papillomavirus–positive cervical cancer cells. However, the exact mechanisms remain poorly characterized. Our studies demonstrated that constitutively overexpressed active Notch1 via stable transfection with exogenous intracellular domain of Notch1 (ICN) resulted in growth inhibition of the human cervical cancer cell line HeLa by inducing G2–M arrest and apoptosis. Moreover, the growth inhibition was correlated with inhibition of nuclear factor kappa B (NF-κB) p50 activation, accompanied by a decrease in the nuclear expression of NF-κB p50 and an increase in the cytosolic expression of IκBα. Consistent with these results, downregulation of cyclin D1 and Bcl-2, which are both the downstream genes of NF-κB, were observed in ICN-overexpressed cells. Overall, our results suggest that NF-κB inhibition may contribute partially to cell cycle arrest and apoptosis induced by Notch1 activation in human cervical cancer cells.

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