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 Anti-Cancer Activity of As4O6 and its Efficacy in a Series of Patient-Derived Xenografts for Human Cervical Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 987
Author(s):  
Joseph J. Noh ◽  
Myeong-Seon Kim ◽  
Young-Jae Cho ◽  
Soo-Young Jeong ◽  
Yoo-Young Lee ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Cancer Cell ◽  
Squamous Cell ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Anti Cancer ◽  
Human Cervical Cancer

Purpose: To investigate the anti-cancer effects of tetraarsenic hexoxide (TAO, As4O6) in cervical cancer cell lines and in a series of patient-derived xenograft (PDX) mouse models. Methods: Human cervical cancer cell lines, including HeLa, SiHa and CaSki, and human umbilical vein endothelial cells (HUVECs), were used to evaluate the anti-cancer activity of TAO. Cellular proliferation, apoptosis, and enzyme-linked immunosorbent assay (ELISA) for matrix metallopeptidase 2 (MMP-2) and 9 (MMP-9) were assessed. The tumor weights of the PDXs that were given TAO were measured. The PDXs included primary squamous cell carcinoma, primary adenocarcinoma, recurrent squamous cell carcinoma, and recurrent adenocarcinoma. Results: TAO significantly decreased cellular proliferation and increased apoptosis in cervical cancer cell lines and HUVEC. The functional studies on the cytotoxicity of TAO revealed that it inhibited the activation of Akt and vascular endothelial growth factor receptor 2 (VEGFR2). It also decreased the concentrations of MMP-2 in both cervical cancer cell lines and HUVECs. Active caspase-3 and p62 were both increased by the treatment of TAO, indicating increased rates of apoptosis and decreased rates of autophagy, respectively. In vivo studies with PDXs revealed that TAO significantly decreased tumor weight for both primary squamous cell carcinoma and adenocarcinoma of the cervix. However, this anti-cancer effect was not seen in PDXs with recurrent cancers. Nevertheless, the combination of TAO with cisplatin significantly decreased tumor weight in PDX models for both primary and recurrent cancers. Conclusions: TAO exerted inhibitory effects on angiogenesis, cellular migration, and autophagy, and it showed stimulatory effects on apoptosis. Overall, it demonstrated anti-cancer effects in animal models for human cervical cancer.

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.

Sensitization of cervical cancer cell lines to low-dose radiation by retinoic acid does not require functional p53

2005 ◽  
Vol 97 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Todd D. Tillmanns ◽  
Scott A. Kamelle ◽  
Suresh Guruswamy ◽  
Natalie S. Gould ◽  
Teresa L. Rutledge ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Retinoic Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Low Dose ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Low Dose Radiation ◽  
Dose Radiation

scholarly journals Adenoviral Vectors Armed with PAPILLOMAVIRUs Oncogene Specific CRISPR/Cas9 Kill Human-Papillomavirus-Induced Cervical Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1934 ◽  
Author(s):  
Eric Ehrke-Schulz ◽  
Sonja Heinemann ◽  
Lukas Schulte ◽  
Maren Schiwon ◽  
Anja Ehrhardt
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Adenoviral Vectors ◽  
Human Papillomaviruses ◽  
Cervical Cancer Cell ◽  
Adenoviral Delivery ◽  
Cervical Cancer Cells

Human papillomaviruses (HPV) cause malignant epithelial cancers including cervical carcinoma, non-melanoma skin and head and neck cancer. They drive tumor development through the expression of their oncoproteins E6 and E7. Designer nucleases were shown to be efficient to specifically destroy HPV16 and HPV18 oncogenes to induce cell cycle arrest and apoptosis. Here, we used high-capacity adenoviral vectors (HCAdVs) expressing the complete CRISPR/Cas9 machinery specific for HPV18-E6 or HPV16-E6. Cervical cancer cell lines SiHa and CaSki containing HPV16 and HeLa cells containing HPV18 genomes integrated into the cellular genome, as well as HPV-negative cancer cells were transduced with HPV-type-specific CRISPR-HCAdV. Upon adenoviral delivery, the expression of HPV-type-specific CRISPR/Cas9 resulted in decreased cell viability of HPV-positive cervical cancer cell lines, whereas HPV-negative cells were unaffected. Transduced cervical cancer cells showed increased apoptosis induction and decreased proliferation compared to untreated or HPV negative control cells. This suggests that HCAdV can serve as HPV-specific cancer gene therapeutic agents when armed with HPV-type-specific CRISPR/Cas9. Based on the versatility of the CRISPR/Cas9 system, we anticipate that our approach can contribute to personalized treatment options specific for the respective HPV type present in each individual tumor.

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