Apoptosis In Cervical Cancer Cells Research Articles

How mesenchymal stem cell conditioned media affect the HeLa cells on Wnt/beta-catenin signaling, Notch-1 signaling, and apoptosis?

This study aims to investigate the influence of mesenchymal stem cells (MSCs) cell-conditioned media (MSCs-CM) on the Wnt/beta-catenin and Notch-1 signaling as well as the apoptosis in cervical cancer cells. Conditioned media of characterized MSCs were freshly collected and filtered before use. HeLa cells cultured standard conditions and treated with MSCs-CM 24, 48, 72 hours. Untreated cells serve as a control. Cell viability measured with MTT assay for all incubation periods. Immunocytochemical staining of beta-catenin, Notch-1 and cleaved caspase 3 were performed for each time-point. MTT cell viability, AO/PI, and immunocytochemical staining of cleaved caspase 3 results showed that through all incubation periods, there was no statistically significant difference between the MSCs-CM treated HeLa cells and the controls (p>0.05). Beta-catenin immunoreactivity was upregulated following treatment from 24 hours to 48 and 72 hours (p

Resveratrol Induces Apoptosis, Suppresses Migration, and Invasion of Cervical Cancer Cells by Inhibiting the Hedgehog Signaling Pathway.

To investigate the effect and mechanism of resveratrol on the biological behavior of cervical cancer cells (HeLa cells), the apoptosis, migration, and invasion of HeLa cells were detected by flow cytometry, wound healing, and transwell assays. The expression levels of Hedgehog signal pathway proteins (smoothened (SMO), zinc finger transcription factors (Gli1), and sonic hedgehog homolog (Shh)) were detected by quantitative real-time PCR (qPCR) and western blotting. Compared with that control group, resveratrol (RES) significantly induced apoptosis, inhibited the migration and invasion of the HeLa cells. The expression of SMO, Gli1, and Shh were downregulated in the HeLa cells treated with RES. The Hedgehog agonist purmorphamine (PUR) reversed the RES-induced increase of apoptosis and reduction of migration and invasion in the HeLa cells. In conclusion, RES induced the apoptosis and suppressed the migration and invasion of HeLa cells by inhibiting Hedgehog signal pathway.

Adiponectin: A player in the pathogenesis of hormone-dependent cancers.

Hormone-dependent cancers are a major cause of morbidity and mortality in both genders. Accumulating evidence suggest that adiponectin, an adipokine with multifaceted functions, is implicated in the pathogenesis of several malignancies. In the present review, we discuss the existing data regarding this relationship. Several observational studies showed that low adiponectin levels are associated with higher risk for breast, cervical, endometrial, ovarian and prostate cancer. A relationship between adiponectin and the aggressiveness of some of these tumors has also been reported. In vitro studies reported that adiponectin inhibits the proliferation and induces apoptosis of breast, cervical, endometrial, ovarian and prostate cancer cells. Given the high prevalence of these cancers and the substantial associated morbidity and mortality, the role of agents that increase adiponectin levels and/or stimulate its activity should be evaluated for the prevention and management of these common tumors.

Effect of NMB-regulated ERK1/2 and p65 signaling pathway on proliferation and apoptosis of cervical cancer.

Aberrant expression of Neuromedin B (NMB) is associated with the malignant progression of cancer, such as breast cancer, lung cancer and glioma. However, the role of NMB in cervical cancer remains unclear. The present study found that NMB and its receptor NMBR are aberrantly expressed in cervical cancer. NMB activates ERK1/2 and NF-κB signaling pathways, which promote the proliferation of cervical cancer cells and increase the expression of tumor necrosis factor α (TNF-α). The downregulation of NMBR by the specific inhibitor, PD168368, abrogates proliferation and promotes apoptosis of cervical cancer cells. In addition, the NMB/NMBR signaling axis mediates the promoting effect of cancer-associated adipocytes on cervical cancer progression. These findings demonstrate the potential role of NMB/NMBR-regulated ERK1/2 and p65 signaling pathway in cervical cancer progression, which provide new opportunities to diagnose and treat cervical cancer.

Ricolinostat suppresses proliferation, promotes apoptosis, and enhances the antiproliferative activity of topoisomerase inhibitors in cervical cancer cells.

Ricolinostat has been found to exhibit anticancer effects alone and in combination with various chemotherapeutic drugs in several cancer types. However, to the best of our knowledge, the efficacy of ricolinostat in cervical cancer is still not investigated. Therefore, in this study, we evaluated the effect of ricolinostat in cervical cancer alone and in combination with topoisomerase inhibitors. The effect of ricolinostat on cervical cancer cells was assessed using MTT, cell-cycle arrest, Annexin V/PI staining assay, reactive oxygen species (ROS) measurement, and western blot analysis. The antiproliferative effect of ricolinostat in combination with topoisomerase inhibitors was assessed using the MTT assay and synergism was computed using "CompuSyn" software. We found that ricolinostat inhibited proliferation, and induced G2/M phase arrest and apoptosis in cervical cancer cells. We further found that ricolinostat treatment resulted in increased ROS production, decreased Bcl-xL expression, and induced p21 expression. We also investigated the effect of ricolinostat in combination with topotecan and etoposide in cervical cancer cells. Ricolinostat was found to significantly enhance the antiproliferative activity of both, topotecan and etoposide, in cervical cancer cells in a concentration-dependent manner. In conclusion, our study showed that ricolinostat suppressed proliferation by inducing G2/M phase arrest and promoted apoptosis in cervical cancer cells, indicating that ricolinostat may be a promising antitumor agent in cervical cancer. Also, ricolinostat and topotecan/etoposide combination are synergistic in cervical cancer cells.

Expression of GMFB in High-Grade Cervical Intraepithelial Neoplasia and Its Role in Cervical Cancer.

Cervical intraepithelial neoplasia (CIN) is a collective term for specific precancerous lesions associated with cervical cancer (CC). Although it has been affirmed with slow development of several levels of cellular changes, the existing poor prognosis calls for an urgent need to diagnose CIN at early stage and be aware of markers related to its pathogenesis and prognosis. We explored the expression level of a newly marker GMFB and its regulatory effect on CIN and CC. Patient samples and cell models were included. Bioinformatic studies were taken to predict its binding to miR-143-3p, miR-26b-5p, miR-191-5p, and miR-223-3p. Luciferase reporter and RNA pull-down assays were used to validate the prediction. Edu assay and flow cytometry were used to measure the regulation of GMFB on proliferation and apoptosis of CC cells. qRT-PCR was used for mRNA expression level detection. The results showed that GMFB was targeted by miR-143-3p, miR-26b-5p, miR-191-5p, and miR-223-3p. It had elevated expression in both CIN and CC samples. GMFB had highly prognostic value for CIN, and lymph node metastasis of CC was much associated with high GMFB expression level. Besides, silencing of GMFB inhibited CC cell proliferation and elevated cell apoptosis. In conclusion, we determined that GMFB has regulatory effect on high grade CIN and CC, which could lighten a novel way in exploring their pathogenesis and improving accuracy of prognosis.

Fbxo22 promotes cervical cancer progression via targeting p57Kip2 for ubiquitination and degradation

F-box only protein 22 (FBXO22) is a key subunit of the Skp1-Cullin 1-F-box protein (SCF) E3 ubiquitin ligase complex. Little is known regarding its biological function and underlying molecular mechanisms in regulating cervical cancer (CC) progression. In this study, we aim to explore the role and mechanism of FBXO22 in CC progression. The correlation between FBXO22 and clinicopathological characteristics of CC was analyzed by tissue microarray. MTT, colony formation, flow cytometry, Western blotting, qRT-PCR, protein half-life, co-immunoprecipitation, ubiquitination, and xenograft experiments were performed to assess the functions of FBXO22 and potential molecular mechanisms of FBXO22-mediated malignant progression in CC. The expression of FBXO22 protein in CC tissues was higher than that in adjacent non-tumor cervical tissues. Notably, high expression of FBXO22 was significantly associated with high histology grades, positive lymph node metastasis, and poor outcomes in CC patients. Functionally, ectopic expression of FBXO22 promoted cell viability in vitro and induced tumor growth in vivo, while knockdown of FBXO22 exhibited opposite effects. In addition, overexpression of FBXO22 promoted G1/S phase progression and inhibited apoptosis in CC cells. Mechanistically, FBXO22 physically interacted with the cyclin-dependent kinase inhibitor p57Kip2 and subsequently mediated its ubiquitination and proteasomal degradation leading to tumor progression. FBXO22 protein level was found negatively associated with p57Kip2 protein levels in patient CC samples. FBXO22 promotes CC progression partly through regulating the ubiquitination and proteasomal degradation of p57Kip2. Our study indicates that FBXO22 might be a novel prognostic biomarker and therapeutic target for CC.

Apoptosis in Human Papillomavirus-Induced Cervical Cancer Cells By Higher Doses of Ascorbic Acid

Objective: To assess the anti-cancer role of ascorbic acid using high doses against the cervical cancer cell line and to establish a cell culture facility in the laboratory.
 Study Design: In Vitro Study.
 Place and Duration of Study: Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi Pakistan, from Aug 2014 to Jul 2015.
 Methodology: HeLa cells were grown in Dulbecco’s modified eagle medium, and upon reaching confluency, cells were challenged with different doses of ascorbic acid. The MTT assay was employed to study the cytotoxic effects of increased doses of ascorbic acid on HeLa cells.
 Results: An increasing dose of ascorbic acid was found to be cytotoxic toward HeLa cells, and its EC50 was found to be between 5-6µM. A high dose of ascorbic acid is selectively cytotoxic to HeLa cell lines of cervical cancer, which may imply the treatment of cervical cancer patients. NF- kB inducing kinase is a salient protein in TNFα-induced NF-kB activation. Ascorbate has been reported to inhibit that activation which has anti-apoptotic roles in tumour progression. CB-Dock was employed to propose the binding sites for NIK-Ascorbate interaction, which might be a therapeutic target for cancer cells.
 Conclusion: The study concludes that high dose ascorbic acid is cytotoxic to cervical cancer cells HeLa and may have important implications in treating cervical cancer patients. Therapeutic intervention of this vitamin may contribute to suppressing cancer development.

In vitro elucidation of antioxidant, antiproliferative, and apoptotic potential of yeast-derived β-1,3-glucan particles against cervical cancer cells.

Cancer is the leading cause of mortality worldwide and in particular is the fourth most common cause of mortality in women every year. Conventional treatments for cancer are chemotherapy and radiation therapy, which have various kinds of side effects. Hence, there is a high need to develop alternative, efficient, and safer therapies for cancer treatment. β-Glucan, a novel polysaccharide isolated from baker's yeast Saccharomyces cerevisiae, shows noteworthy cytotoxicity toward a variety of cancer cell lines in vitro. In this research, we characterized the β-glucan with high-performance thin-layer chromatography (HPTLC) analysis and found that d-glucose units with β-1,3 links are the major component of the extracted β-glucan particles. Fourier transform IR (FTIR) analysis confirmed a β-(1→3)-linked glucan structure. In vitro cell cytotoxicity was evaluated by MTT with IC50 136 μg/ml, and therapeutic potential was assessed by various assays using values below and above the IC50. A significant reactive oxygen species (ROS) generation at 50-150 μg/ml of concentrations indicated the apoptosis of cervical cancer cells. Along with ROS generation, these concentrations were also found to induce morphological changes such as fragmentation in DNA upon staining HeLa cells with DAPI. Mitochondrial membrane potential was significantly reduced after increasing the dose of treatment, assessed with the help of MitoTracker dye. Hence, by all these experimental supports, we observed that β-glucan has the potential to slow down the growth of cervical cancer cells, and it can be further investigated for unfolding its complete anticancer potential.

Cytotoxic effect and induction of apoptosis in human cervical cancer cells by a wood extract from Prosopis laevigata

Cervical cancer ranks fourth in incidence among women worldwide. Cisplatin is currently the first-line drug of treatment for cervical cancer; however, it causes serious adverse effects. Therefore, it is crucial to explore natural products for cervical cancer treatment. Prosopis laevigata is a medicinal plant frequently used for ophthalmological and gastrointestinal infections. In this study, we used the MTT cell viability assay to evaluate the cytotoxic effect of a wood extract from Prosopis laevigata (Extract T7) in SiHa, HeLa, Ca Ski, and C-33 A cancer cell lines. Phosphatidylserine translocation and cell cycle evaluations were performed to determine the mechanism of cellular death. The extract's safety was evaluated using the Ames test with Salmonella typhimurium strains, in vivo acute toxicity assay, and repeated dose toxicity assay in mice. We also identified phenolic compounds of Extract T7 through liquid chromatography/mass spectrometry. Naringin, catechin, and eriodictyol demonstrated a higher concentration in Extract T7. Additionally, Extract T7 exhibited a cytotoxic effect against cervical cancer cells, where C-33 A was the most sensitive (IC50= 22.58 ± 1.10 µg/mL and 14.26 ± 1.11 µg/mL at 24 h and 48 h respectively). Extract T7 induced death by apoptosis and cell cycle arrest in the G2 phase in C-33 A. Extract T7 was not mutagenic. No toxicological effects were observed during acute toxicity and repeated dose toxicity for 28 days. Therefore, further evaluations of Extract T7 should be conducted to identify the complete mechanism of action for potential anti-tumoral activity and safety before conducting studies in animal models.

Plasma activated medium prepared by a bipolar microsecond-pulsed atmospheric pressure plasma jet array induces mitochondria-mediated apoptosis in human cervical cancer cells.

Plasma activated medium (PAM) was prepared by a bipolar microsecond-pulsed atmospheric pressure plasma jet (APPJ) array source and was utilized for cancer cell treatment. APPJ array-produced plasma were characterized. APPJ array treatment of three different solutions (deionized water (DW), HBSS (serum-free Hanks’ balanced salt solution), and DMEM (Dulbecco’s Modified Eagle Medium) + 10% FBS (fetal bovine serum)) were performed to induce the changes in the concentration of reactive oxygen and nitrogen species (RONS) as functions of the operating parameters. Human cervical cancer cells (HeLa) injected with plasma-treated media were investigated for changes in cell viability using MTT assay. It was observed that PAM-induced ROS can regulate the protein expression associated with mitochondria, and PAM causes apoptosis through Cyto C/JNK/p38 signaling on human cervical cancer cells.

Standardized phytopreparations and cucurbitacin IIb from Ibervillea sonorae (S. Watson) greene induce apoptosis in cervical cancer cells by Nrf2 inhibition

Ethnopharmacology relevanceIbervillea sonorae (S. Watson) Greene is a plant from northwestern Mexico, known as “Wereke” or “Guareque”, used by the Mayo ethnic group to treat diabetes and cancer. Cucurbitacin IIb (CIIb), isolated from I. sonorae has apoptotic and antitumor activity in a model of cervical cancer with the HeLa cell line. One pathway affected by cucurbitacins is Nrf2, a glutathione transferase (GST) transcription factor, important in the regulation of mitochondrial oxidative stress (MOS). A signal of MOS is the change in the mitochondrial membrane potential (ΔΨm), which has been detected in HeLa in the presence of CIIb. Fito-Ison-EtOH (Etanison) and Fito-Ison-EtOAc (Acetison) are phytopreparations from I. sonorae standardized according to their CIIb content (6.7 mg/g and 18.4 mg/g of CIIb, respectively). Etanison and Acetison have been reported to induce morphological changes in HeLa like those induced by CIIb. Aim of the studyTo evaluate the apoptotic and Nrf2 inhibition activity of the phytopreparations Acetison and Etanison from Ibervillea Sonorae in the HeLa cervical cancer cell line. Materials and methodsAntiproliferative activity was evaluated by the MTT method at 24, 48, and 72 h. For Acetison and Etanison, serial concentrations from 6.25 μg/mL to 100 μg/mL were tested, and for CIIb from 1.56 μg/mL to 50 μg/mL. The expression of Nrf2, caspase 3, and caspase 9 was evaluated by western blot, using concentrations of 30 μg/mL for Acetison, 50 μg/mL for Etanison, and 15 μg/mL for CIIb. Cisplatin was used as a positive control. Results and conclusionsApoptotic activity of Etanison and Acetison was demonstrated in HeLa, due to the presence of caspase-9 and caspase-3 in western blot assays. Likewise, both the phytopreparations and CIIb showed inhibition of Nrf2, associating apoptotic activity with the inhibition of the GST transcription factor. In this sense, the phytopreparations of I. sonorae, as well as their derivatives, have the potential to obtain and develop anticancer products.

Deficiency of kin17 Facilitates Apoptosis of Cervical Cancer Cells by Modulating Caspase 3, PARP, and Bcl-2 Family Proteins.

Background The treatment of cervical cancer in the late stage is still quite challenging, because of nonspecificity in conventional therapies and the lack of molecular targeted drugs. It is necessary to find novel biomarkers for cervical cancer treatment. Methods In the present study, cervical cell lines HeLa and SiHa with kin17 knockdown were constructed by transfection of the recombinant lentiviral vector carrying KIN17 siRNA and screened by puromycin. The established cells with kin17 knockdown were determined by fluorescence observation and western blotting. Cell apoptosis and the mitochondrial membrane potential (MMP) were detected by flow cytometry. The activity of caspase 3 enzyme was tested by spectrophotometry. The expression profile of apoptosis-associated proteins was analyzed by western blotting. Finally, we used bioinformatics and proteomic data to analyze KIN-related genes in cervical cancer. Results The results showed high fluorescent positive rates (>90%) and high gene silencing efficiency (>65%) in HeLa and SiHa cells transfected with gene silencing vectors. Moreover, kin17 deficiency decreased the MMP and increased the apoptosis rates in HeLa and SiHa cells, respectively. Furthermore, knockdown of kin17 enhanced the activity of caspase 3 enzyme, increased the expression of cleaved PARP and Bim, while decreasing the expression of Bcl-xL and phosphorylated BAD in HeLa and SiHa cells. Identification of KIN-related prognostic genes in cervical cancer revealed that a total of 5 genes (FZR1, IMPDH1, GPKOW, XPA, and DDX39A) were constructed for this risk score, and the results showed that CTLA4 expressions were negatively correlated with the risk score. Conclusion Our findings demonstrated that kin17 knockdown facilitates apoptosis of cervical cancer cells by targeting caspase 3, PARP, and Bcl-2 family proteins. Besides, kin17 could regulate cancer cell apoptosis through the mitochondrial pathway and could be used as a novel therapeutic target for the regulation of cell apoptosis in cervical cancer.

Juglone induces proliferation inhibition and apoptosis of cervical cancer cells via promoting c-Myc ubiquitination

To observe the expression of c-Myc protein in cervical cancer HeLa cells and explore the effect of juglone on the proliferation and apoptosis of HeLa cells by affecting c-Myc ubiquitination. HeLa cells treated with different concentrations (0, 10, 20, or 50 μmol/L) of juglone or with 20 μmol/L juglone for different time lengths were examined for expression of c-Myc protein with Western blotting. The half-life of c-Myc protein was determined using cycloheximide (CHX) and c-Myc protein degradation was detected using coimmunoprecipitation. We also assessed the effects of 20 μmol/L juglone combined with 0, 1.0 or 2.0 μmol/L MG132 (a proteasome inhibitor) on c-Myc expression. The effects of 20 μmol/L juglone on the proliferation and apoptosis of HeLa cells with RNA interference-mediated knockdown of c-Myc were evaluated with MTT assay and flow cytometry. Treatment with juglone significantly lowered c-Myc protein expression in HeLa cells in a concentration-and time-dependent manner (P < 0.05). Juglone obviously shortened the half-life of c-Myc protein, and the addition of MG132 significantly up-regulated the expression level of c-Myc protein (P < 0.05). Juglone treatment also promoted ubiquitination of c-Myc protein in HeLa cells. Compared with the cells transfected with a negative control construct, the cells transfected with si-c-Myc showed significantly decreased proliferation inhibition and a lowered cell rate with early apoptosis after juglone treatment (P < 0.05). Juglone inhibits proliferation and promotes apoptosis of HeLa cells by affecting the ubiquitination of c-Myc protein.

Annexin A5 suppression promotes the progression of cervical cancer.

Cervical cancer is a common malignant gynecological disease that threatens the health of women all over the world. The abnormal expression of Annexin A5 (ANXA5) is closely related to the biological behavior of various malignant tumors, however, the relationship between ANXA5 and cervical cancer is still unclear. Therefore, the effects of low expression of ANXA5 on the proliferation, apoptosis, migration and invasion of cervical cancer cells (HeLa) and its related mechanism were explored. The cells were divided into three groups: ANXA5-si group, negative control group and blank group. RNA interference was used to suppress ANXA5 expression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, flow cytometry and propidium iodide (PI) staining, wound healing assay and transwell assay were employed to detect cell proliferation, apoptosis, migration and invasion respectively. Meanwhile, gene expression was detected by qPCR and Western blotting. ANXA5 suppression lead to the increase of proliferation, migration, invasion and the decrease of apoptosis of cervical cancer HeLa cells. Furthermore, the expression of both pPI3K and pAkt increased. ANXA5 might inhibit Hela cells proliferation and metastasis by regulating PI3K/Akt signal pathway.

Influences of Total Alkaloids in Caulis Mahoniae on Proliferation and Apoptosis of Cervical Cancer Cells and the Caspase-3 Expression.

The study aimed to investigate the influences of the active ingredient in Caulis Mahoniae, total alkaloids, on the proliferation and apoptosis of cervical cancer cells and the caspase-3 expression. The total alkaloids were extracted in vitro from Caulis Mahoniae, and cervical cancer HeLa cell lines were used as experimental objects. The half inhibitory concentration (IC50) of total alkaloids on HeLa cell lines was detected via the preliminary experiment, the influences of total alkaloids at different concentrations on the proliferation of HeLa cell lines were detected via methyl thiazolyl tetrazolium (MTT) assay, and the cell growth curve was plotted. Moreover, the cell cycle and apoptosis after treatment with total alkaloids at different concentrations were detected via flow cytometry, and the caspase-3 gene and protein expressions were detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The IC50 of total alkaloids in Caulis Mahoniaeon HeLa cell lines was 12.5 μg/mL. With the gradual increase of concentration of total alkaloids in the treatment of cervical cancer cells, the inhibitory rate on cancer cells was gradually increased, and the proportion of cells in the G0/G1 phase was gradually decreased, while that in S and G2/M phases was gradually increased. Besides, with the increase in the concentration of total alkaloids, the apoptotic rate of cervical cancer cells was gradually increased, and both caspase-3 gene and protein expressions were also gradually increased. The total alkaloids extracted from Caulis Mahoniae can effectively inhibit the proliferation and promote the apoptosis of cervical cancer HeLa cells, which may be realized by promoting the expression of apoptosis-related factor caspase-3.

Synthesis and Anticancer Activity of Rhopaladins' Analog RPDPD Against the HeLa Human Cervical Cancer Cell Line.

Heterocyclic compounds were widely used in many domains; pyrrolidone is a derivative of heterocycles that can be used to synthesize anticancer drugs. A new fluorine-containing rhopaladins’ analog(E)-2-(4-bromobenzoyl)-N-(tert-butyl)-4-(4-fluoro benzylidene)-5-oxo-1-propylpyrrolidine-2-carboxamide (RPDPD for short) of 2-aroyl-4-arylidene-5-oxopyrrolidine derivative was synthesized by the one-pot synthesis method and evaluated for its anti-tumor activity in vitro via CCK8 assay and annexin V/propidium iodide (PI) staining of HeLa cells. The results exhibited that compound RPDPD has inhibited the proliferation of HeLa in a dose-dependent manner with an IC50 of 24.23 μmol/L (p < 0.05) and has low hepatotoxicity with an IC50 of 235.6 μmol/L (p < 0.05) to normal hepatocyte LO2 cells. The apoptotic assay demonstrated that compound RPDPD has induced apoptosis in HeLa cells (from 14.26 to 23.4%, p < 0.05). qRT-PCR results showed that the compound RPDPD could inhibit the expression of oncogene E6/E7 mRNA (p < 0.05) of human papillomavirus (HPV). The results of Western blot showed that the compound RPDPD promoted the expression of TIMP3 protein and inhibited the expression of MMP3 (p < 0.05). In conclusion, the compound RPDPD can inhibit the proliferation of cervical cancer cells and induce the apoptosis of cervical cancer cells, and its mechanism may be related to the inhibition of E6 mRNA and E7 mRNA expressions, and the anticancer effect of the compound RPDPD on cervical cancer is closely related to the TIMP3/MMP3 signaling axis.

Curcumenol Targeting YWHAG Inhibits the Pentose Phosphate Pathway and Enhances Antitumor Effects of Cisplatin.

Objective Cervical cancer is a common cancer in women. The drug resistance of chemotherapeutic agents has always been an urgent problem to be solved in clinics. The purpose of this study was to determine the role of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma polypeptide (YWHAG) in cervical cancer and explore the effect of Curcuma on cervical cancer and its possible mechanism. Methods YWHAG expression in cervical cancer was confirmed using The Cancer Genome Atlas (TCGA) database. Then, the effects of YWHAG on the proliferation and invasion of HeLa and C33A cervical cancer cells were detected by the cell counting kit-8 (CCK-8) and transwell assay. The relationship between YWHAG and the pentose phosphorylation pathway was further studied. CCK-8, Edu, and quantitative real-time polymerase chain reaction were used to confirm that Curcuma inhibited the sensitivity of YWHAG to cisplatin chemotherapy and to detect the expression of apoptosis-related proteins. Results YWHAG was highly expressed in cervical cancer and was associated with poor prognosis. The proliferation and invasion abilities of HeLa and C33A cells decreased after YWHAG knockout. The TCGA database of cervical cancer showed a positive correlation between YWHAG and hypoxia-inducible factor-1 subunit alpha (HIF-1α) expression. YWHAG expression increased with HIF-1α overexpression. YWHAG knockdown reduced the protein expression in the pentose phosphorylation pathway. Curcumenol inhibited YWHAG expression. Compared with cisplatin alone, curcumenol combined with cisplatin can reduce cell proliferation and invasion and reduce matrix metalloproteinase (MMP) 2 and MMP9 expression. It can also increase apoptosis, decrease B cell lymphoma 2 (Bcl-2) expression, and increase the expression of Bcl-2 antagonist X, caspase-3, and polyadenosine diphosphate-ribose polymerase. Conclusion YWHAG can interact with HIF-1α to affect the proliferation and invasion of cervical cancer cells. YWHAG knockout can reduce the expression of pentose phosphorylation pathway-related proteins. Curcumenol can enhance cisplatin to inhibit cancer cell proliferation, migration, and invasion and promote tumor cell apoptosis. The combination of drugs may promote the apoptosis of cervical cancer cells through the YWHAG pathway.

LncRNA FAM13A-AS1 Regulates Proliferation and Apoptosis of Cervical Cancer Cells by Targeting miRNA-205-3p/DDI2 Axis.

The aim of this study was to explore the function of long noncoding RNA (lncRNA) FAM13A-AS1 and its associated mechanism in cervical cancer. A total of 30 cervical cancer tissues and adjacent tissues were collected. Cervical cancer cell lines, including SiHa and HeLa, were transfected with constructs expressing LV-FAM13A-AS1, silencing RNA LV-siFAM13A-AS1, miRNA mimics, and miRNA inhibitors. RT-qPCR was used to detect the expression of FAM13A-AS1 in cervical cancer tissues, including SiHa, HeLa, and HUCEC cells. MTT, flow cytometry, and transwell assays were performed to explore the influence of FAM13A-AS1 on cervical cancer cell proliferation, apoptosis, invasion, and migration. A bioinformatics analysis and a dual-luciferase assay were carried to confirm the target relationship between FAM13A-AS1 or DDI2 and miRNA-205-3p. Finally, in vivo tumorigenesis experiments were performed in nude mice to explore the effect of FAM13A-AS1 expression on cervical cancer. Low FAM13A-AS1 expression and high miRNA-205-3p expression were observed in cervical cancer tissues and cell lines (SiHa and HeLa). Upregulating the expression of FAM13A-AS1 inhibited proliferation, migration, and invasion of SiHa and HeLa cells, while the apoptosis of SiHa and HeLa cells was increased. More importantly, LV-FAM13A-AS1 could improve tumor development in vivo. In addition, FAM13A-AS1 negatively regulated the expression of miRNA-205-3p, while miRNA-205-3p reduced DDI2 expression, and miRNA-205-3p mimic reversed the effects of FAM13A-AS1 overexpression in vitro. In conclusion, FAM13A-AS1 inhibits the progression of cervical cancer by targeting the miRNA-205-3p/DDI2 axis, suggesting that FAM13A-AS1 might be a potential target for cancer cell treatment.

PLGA-Quercetin Nano-Formulation Inhibits Cancer Progression via Mitochondrial Dependent Caspase-3,7 and Independent FoxO1 Activation with Concomitant PI3K/AKT Suppression.

Quercetin is one of the most important plant flavanols, having several pharmacological and biological uses. Quercetin (Q) is an extremely hydrophobic phytochemical and has poor intracellular absorption, which makes its use limited. Present research demonstrates that quercetin-loaded PLGA nanoparticles (PLGA-QNPs) could overcome its low hydrophilicity and improve its anti-cancer potential. PLGA nanoparticles loaded with Q were prepared by the solvent evaporation technique and its anticancer activity was examined in vitro as well as in vivo. The cell viability was assessed through MTT assay and apoptosis was assayed through Hoechst-PI and EB/AO double staining followed by mitochondrial damage through Mito-tracker RMX-Ros. Gene expression was examined through RT-PCR. Cell cycle arrest in G2/M phase was analyzed through FACS. The results obtained revealed that PLGA-QNPs significantly reduced the viability of human cervical and breast cancer cell lines. PLGA-QNPs induced apoptosis in human cervical cancer cells in a dose dependent manner. The gene expression of PI3K/AKT was down-regulated and FoxO1 was upregulated in PLGA-QNP-treated cells, which showed a high expression level of active Caspase-3 and 7, which are responsible for apoptosis. In addition, PLGA-QNPs reduced the average number of tumors and prolonged the tumor latency period in DMBA-induced mammary adenocarcinoma SD rats. These findings suggest that PLGA-QNPs inhibit cervical and breast cancer progression via mitochondrial dependent Caspase-3 and 7 and mitochondrial independent FoxO1 activation with concomitant suppression of the PI3K/AKT pathway. For future studies, we suggest that potential druggability efficacy and clinical development of anticancer PLGA-QNPs need to be evaluated intensely for successful anticancer drug development.