scholarly journals Activation of the retinoblastoma tumor suppressor mediates cell cycle inhibition and cell death in specific cervical cancer cell lines

2009 ◽  
Vol 48 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Ryan J. Bourgo ◽  
Wesley A. Braden ◽  
Susanne I. Wells ◽  
Erik S. Knudsen
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Death ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Retinoblastoma Tumor Suppressor ◽  
Cell Cycle Inhibition ◽  
Retinoblastoma Tumor

scholarly journals Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer

2020 ◽  
Vol 295 (50) ◽  
pp. 17169-17186
Author(s):  
Mysore S. Veena ◽  
Santanu Raychaudhuri ◽  
Saroj K. Basak ◽  
Natarajan Venkatesan ◽  
Parameet Kumar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Dna Damage ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
S Phase ◽  
Cervical Cancer Cell ◽  
Damage Response

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3′ terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys382-p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G1-S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors.

Chrysin rich Scutellaria discolor Colebr. induces cervical cancer cell death via the induction of cell cycle arrest and caspase-dependent apoptosis

Life Sciences ◽  
2015 ◽  
Vol 143 ◽  
pp. 105-113 ◽  
Author(s):  
Surbala Laishram ◽  
Dinesh Singh Moirangthem ◽  
Jagat Chandra Borah ◽  
Bikas Chandra Pal ◽  
Pankaj Suman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cancer Cell Death ◽  
Cycle Arrest

scholarly journals Anti-cancer property of Lenzites betulina (L) Fr. on cervical cancer cell lines and its anti-tumor effect on HeLa-implanted mice

2019 ◽  
Author(s):  
Tapojyoti Sanyal ◽  
Swapan Kumar Ghosh
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Hela Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Morphology ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Dapi Staining ◽  
Anti Cancer

AbstractIn global scenario cervical cancer is increasing. New drugs from natural compounds are in search. Mushrooms are now recognized as miniature pharmaceutical factories producing hundreds of novel constituents. We have taken ethanolic extract Lenzities betulina (LBE) wild mushroom for evaluation of its as anti-cancer property against cervical cancer cell lines e.g. HeLa, CaSki and SiHa and anti tumor activity against HeLa implanted tumor on mice. The extraction was done by dip and stirring method in 90% ethanol for 72 h. For evaluation of anti-cervical cancer, several assays were performed such as MTT assay, cell morphology by phase contrast microscope and F-action polymerization by Laser scanning confocal microscope and nuclear morphology DAPI staining under inverted fluorescence microscope, MMP, ROS, cell cycle, autophagy and stem cell population by flow cytometry and DNA laddering were done. Western blotting was done for protein expression. To evaluate anti-metastatic activity, anti-cologenic assay and wound healing assay were adopted. For chemo-analysis of the LBE, GC-MS was done. The results from Cytotoxicity assay showed that at highest dose of LBE (1000 µg/ml) after 24 h, percentage of cell inhibitions were 85.13 %, 77.13 % and 47.70 % against HeLa, CaSki and SiHa respectively and the calculated IC50 values were 492.52 ± 2.6 µg/ml, 612.22 ± 4.2 µg/ml, and 1210.30 ± 6.4 µg/ml respectively. Depending upon the cytotoxicity screening, HeLa cell line was considered for the further studies. Cell morphology study exhibited that LBE treated HeLa cells became round from normal spindle shape. DAPI staining showed that LBE treated nucleus became condensed and fragmented. DNA fragmentation at 230 and 300 base pair zone from agarose gel assay was observed. LBE induced ROS generation and reduced MMP. It up regulated the expression of apoptotic genes and p53 while down regulated Bcl2, pro-caspase 3 and pro caspase-9 gene. Cell cycle was arrested at G2/M checkpoint. Autophagic induction was exhibited by vacuole formation in treated cells. CSC population of treated cells was reduced and F-actin polymerization was observed in treated cells. In addition, LBE suppressed metastatic nature by inhibition of cell migration and colonization. The inhibition of growth of the tumors in HeLa cell-implanted mice showed that treatment with 50 mg LBE/kg of body weight of mice led to a marked reduction in the volume (93.22 ± 9.2 %) and weight (90.42 ±9.55 %) of the tumors. The GC-MS profile of LBE shows that out of 69 compounds, 9, 12-Octadecadienoic acid (Z, Z) and Ergosta-5, 8, 22-trien-3-ol, (3.beta22E) are in a significantly higher proportion with the percentage peak area 22.13 and 19.72 respectively. Library search for bioactivity showed that these compounds are anti-cancerous and interestingly 4’-Hydroxy-6-methoxyaurone binding with P-glycoprotein inhibits the cancer cells to become drug resistant. In conclusion, LBE is very prominent anti-cervical cancer having a lot of anti-cancerous compounds which are probably acting synergistically. This report of anti-cervical cancer property of L. betulina is probably first time in oncology. Its therapeutic use in human model is urgent for new drug development.

scholarly journals Proteomics Analysis of Andrographolide-Induced Apoptosis Via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines

2021 ◽  
Vol 22 (13) ◽  
pp. 6806
Author(s):  
Pariyakorn Udomwan ◽  
Chamsai Pientong ◽  
Panwad Tongchai ◽  
Ati Burassakarn ◽  
Nuchsupha Sunthamala ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Papillomaviruses ◽  
Cervical Cancer Cell ◽  
World Population ◽  
Cervical Cancer Cells

Regardless of the prophylactic vaccine accessibility, persistent infections of high-risk human papillomaviruses (hr-HPVs), recognized as an etiology of cervical cancers, continues to represent a major health problem for the world population. An overexpression of viral early protein 6 (E6) is linked to carcinogenesis. E6 induces anti-apoptosis by degrading tumor suppressor proteins p53 (p53) via E6-E6-associated protein (E6AP)-mediated polyubiquitination. Thus, the restoration of apoptosis by interfering with the E6 function has been proposed as a selective medicinal strategy. This study aimed to determine the activities of andrographolide (Androg) on the disturbance of E6-mediated p53 degradation in cervical cancer cell lines using a proteomic approach. These results demonstrated that Androg could restore the intracellular p53 level, leading to apoptosis-induced cell death in HPV16-positive cervical cancer cell lines, SiHa and CaSki. Mechanistically, the anti-tumor activity of Androg essentially relied on the reduction in host cell proteins, which are associated with ubiquitin-mediated proteolysis pathways, particularly HERC4 and SMURF2. They are gradually suppressed in Androg-treated HPV16-positive cervical cancer cells. Collectively, the restoration of p53 in HPV16-positive cervical cancer cells might be achieved by disruption of E3 ubiquitin ligase activity by Androg, which could be an alternative treatment for HPV-associated epithelial lesions.

scholarly journals UVB Inhibits Proliferation, Cell Cycle and Induces Apoptosis via p53, E2F1 and Microtubules System in Cervical Cancer Cell Lines

2021 ◽  
Vol 22 (10) ◽  
pp. 5197
Author(s):  
Angelica Judith Granados-López ◽  
Eduardo Manzanares-Acuña ◽  
Yamilé López-Hernández ◽  
Julio Enrique Castañeda-Delgado ◽  
Ixamail Fraire-Soto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cellular Damage ◽  
Cervical Cancer Cell ◽  
Skin Damage ◽  
Cellular Processes ◽  
Tubulin Protein

Ultraviolet (UV) exposure has been linked to skin damage and carcinogenesis, but recently UVB has been proposed as a therapeutic approach for cancer. Herein, we investigated the cellular and molecular effects of UVB in immortal and tumorigenic HPV positive and negative cells. Cells were irradiated with 220.5 to 1102.5 J/m2 of UVB and cell proliferation was evaluated by crystal violet, while cell cycle arrest and apoptosis analysis were performed through flow cytometry. UVB effect on cells was recorded at 661.5 J/m2 and it was exacerbated at 1102.5 J/m2. All cell lines were affected by proliferation inhibition, cell cycle ablation and apoptosis induction, with different degrees depending on tumorigenesis level or HPV type. Analysis of the well-known UV-responsive p53, E2F1 and microtubules system proteins was performed in SiHa cells in response to UVB through Western-blotting assays. E2F1 and the Microtubule-associated protein 2 (MAP2) expression decrease correlated with cellular processes alteration while p53 and Microtubule-associated Protein 1S (MAP1S) expression switch was observed since 882 J/m2, suggesting they were required under more severe cellular damage. However, expression transition of α-Tubulin3C and β-Tubulin was abruptly noticed until 1102.5 J/m2 and particularly, γ-Tubulin protein expression remained without alteration. This study provides insights into the effect of UVB in cervical cancer cell lines.

scholarly journals Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3963 ◽  
Author(s):  
Izabela N. Faria Gomes ◽  
Renato J. Silva-Oliveira ◽  
Viviane A. Oliveira Silva ◽  
Marcela N. Rosa ◽  
Patrik S. Vital ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Migration And Invasion ◽  
Cycle Arrest

Plant-based compounds are an option to explore and perhaps overcome the limitations of current antitumor treatments. Annona coriacea Mart. is a plant with a broad spectrum of biological activities, but its antitumor activity is still unclear. The purpose of our study was to determine the effects of A. coriacea fractions on a panel of cervical cancer cell lines and a normal keratinocyte cell line. The antitumor effect was investigated in vitro by viability assays, cell cycle, apoptosis, migration, and invasion assays. Intracellular signaling was assessed by Western blot, and major compounds were identified by mass spectrometry. All fractions exhibited a cytotoxic effect on cisplatin-resistant cell lines, SiHa and HeLa. C3 and C5 were significantly more cytotoxic and selective than cisplatin in SiHa and Hela cells. However, in CaSki, a cisplatin-sensitive cell line, the compounds did not demonstrate higher cytotoxicity when compared with cisplatin. Alkaloids and acetogenins were the main compounds identified in the fractions. These fractions also markedly decreased cell proliferation with p21 increase and cell cycle arrest in G2/M. These effects were accompanied by an increase of H2AX phosphorylation levels and DNA damage index. In addition, fractions C3 and C5 promoted p62 accumulation and decrease of LC3II, as well as acid vesicle levels, indicating the inhibition of autophagic flow. These findings suggest that A. coriacea fractions may become effective antineoplastic drugs and highlight the autophagy inhibition properties of these fractions in sensitizing cervical cancer cells to treatment.

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