Proliferation Of HeLa Research Articles

Structure-based design, synthesis and biological evaluation of aminopyrazines as highly potent, selective, and cellularly active allosteric SHP2 inhibitors

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) encoded by the proto-oncogene PTPN11 is the first identified non-receptor protein tyrosine phosphatase. SHP2 dysregulation contributes to the pathogenesis of different cancers, making SHP2 a promising therapeutic target for cancer therapy. In this article, we report the structure-guided design based on the well-characterized SHP2 inhibitor SHP099, extensive structure-activity relationship studies (SARs) of aminopyrazines, biochemical characterization and cellular potency. These medicinal chemistry efforts lead to the discovery of the lead compound TK-453, which potently inhibits SHP2 (SHP2WT IC50 = 0.023 μM, ΔTm = 7.01 °C) in a reversible and noncompetitive manner. TK-453 exhibits high selectivity over SHP2PTP, SHP1 and PTP1B, and may bind at the “tunnel” allosteric site of SHP2 as SHP099. As the key pharmacophore, the aminopyrazine scaffold not only reorganizes the cationic-π stacking interaction with R111 via the novel hydrogen bond interaction between the S atom of thioether linker and T219, but also mediates a hydrogen bond with E250. In vitro studies indicate that TK-453 inhibits proliferation of HeLa, KYSE-70 and THP-1 cells moderately and induces apoptosis of Hela cells. Further mechanistic studies suggest that TK-453 can decrease the phosphorylation levels of AKT and Erk1/2 in HeLa and KYSE-70 cells. Collectively, TK-453 is a highly potent, selective, and cellularly active allosteric SHP2 inhibitor that modulates the phosphorylation of SHP2-mediated AKT and Erk cell signaling pathways by inhibiting the phosphatase activity of SHP2.

In Vitro Anticancer Activity of Imperata cylindrica Root's Extract toward Human Cervical Cancer and Identification of Potential Bioactive Compounds.

Imperata cylindrica is traditionally used to cure several diseases including cancer, wounds, and hypertension. The present study was designed to investigate the anticancer activity of the methanolic root extract of I. cylindrica (IC-MeOH). The water-soluble tetrazolium-1 and colony formation assays were used to check the proliferation ability of the cells. Cell apoptosis and cell cycle were measured by flow cytometry-based fluorescence-activated cell sorting. The ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analysis was used for the metabolites profiling of IC-MeOH. Based on high-mass accuracy, spectral data, and previous reports, tentative compound identifications were assigned. Our findings revealed that IC-MeOH inhibited the proliferation of HeLa and CaSki cells. The plant extract was also found to induce a concentration- and time-dependent apoptosis and cell cycle arrest in the G0/G1 phase (IC50 value) in CaSki cell line. Analysis of IC-MeOH permitted the identification of 10 compounds already reported for their anticancer activity, epicatechin, curcumin, (-)-yatein, caffeic acid, myricetin, jatrorrhizine, harmaline, cinnamaldehyde, dobutamine, and syringin. In conclusion, IC-MeOH is a rich source of cytotoxic metabolites that inhibits human cervical cancer proliferation via apoptosis and cell cycle arrest.

Increased Nuclear Transporter Importin 7 Contributes to the Tumor Growth and Correlates With CD8 T Cell Infiltration in Cervical Cancer.

Background: Importin 7 (IPO7), a karyopherin-β protein, is involved in various tumorigenesis and progression abilities by mediating the nuclear import of oncoproteins. However, the exact biological functions of IPO7 remain to be further elucidated.Materials and Methods: TCGA and GEO datasets were used to identify dysregulated expression of IPO7 in various cancers. Gain-of-function and loss-of-function analyses were used to identify the oncogenic functions of IPO7 in vitro and in vivo. Moreover, LC-MS/MS and parallel reaction monitoring analysis were used to comparatively profiled IPO7-related proteomics and potential molecular machinery.Results: Our works demonstrated that the expression of IPO7 was upregulated and was correlated with a poor prognosis in cervical cancer. In vitro and in vivo experiments demonstrated that knockdown of IPO7 inhibited the proliferation of HeLa and C-4 I cells. LC-MS/MS analysis showed that IPO7-related cargo proteins mainly were enriched in gene transcription regulation. Then independent PRM analysis for the first time demonstrated that 32 novel IPO7 cargo proteins, such as GTF2I, RORC1, PSPC1, and RBM25. Moreover, IPO7 contributed to activating the PI3K/AKT-mTOR pathway by mediating the nuclear import of GTF2I in cervical cancer cells. Intriguingly, we found that the IPO7 expression was negatively correlated with CD8 T cell infiltration via regulating the expression of CD276 in cervical cancer.Conclusion: This study enhances our understanding of IPO7 nuclear-cytoplasmic translocation and might reveal novel potential therapeutic targets. The results of a negative correlation between the IPO7 and CD8 T cell infiltration indicate that the IPO7 might play an important impact on the immune microenvironment of cervical cancer.

Evaluation of Antimicrobial and Anticancer Activities of Bouea macrophylla Ethanol Extract.

The Bouea macrophylla (B. macrophylla) tree is widely grown throughout South East Asia and has been used as a traditional medicine for the treatment of various illnesses. This chapter presents a protocol for preparation of ethanol extracts of B. macrophylla leaves and evaluation of the potential antimicrobial and anticancer activities in vitro. The extract displayed antibacterial activity against nine out of the ten target microorganisms tested. In addition, the extract was capable of inhibiting the proliferation of HeLa and HCT116 cells, thus demonstrating some anticancer activity.

Dexmedetomidine Inhibited Proliferation and Invasion of Cervical Cancer Cells by Inhibiting the Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription Signaling Pathway

The role of anesthetics in the treatment of cancer has been reported, but the role of Dexmedetomidine (Dex) in the treatment of cervical cancer (CC) has not been reported.In this study, cell viability and proliferation were determined by MTT and cloning formation assay. The expression of proliferation-related proteins ki67 and PCNA was detected by western blot. Wound healing and transwell detected cell migration and invasion, and western blot detected the expression of migration and invasion related proteins MMP4 and MMP9, and epithelial-mesenchymal transformation (ETM)-related proteins N-cadherin, Snail, Vimentin and E-cadherin. Western blot also detected the expression of pathway related proteins p-JAK2, p-STAT1, p-STAT3, JAK2, STAT1 and STAT3. It showed that Dex inhibited the cell viability and proliferation of Hela and siHa and the expression of ki67 and PCNA were also inhibited. Dex inhibited the cell migration and invasion, and inhibited the expression of MMP4 and MMP9. In addition, Dex inhibited the expression of N-cadherin, Snail and Vimentin, and promoted the expression of E-cadherin. Dex inhibited the expression of p-JAK2, p-STAT1 and p-STAT3. After the addition of JAK/STAT signaling pathway agonist IL-6, the inhibition of Dex on proliferation, migration and invasion of CC cells was reversed. And the addition of JAK/STAT signaling pathway inhibitor AG490 could counteract the excitatory effect of IL-6 on the pathway, at which time the cell proliferation, invasion and migration were significantly increased. In conclusion, our study demonstrated that Dex inhibited proliferation, migration, and invasion of cells in CC by blocking the JAK/STAT signaling pathway.

Evaluation on bioactivities of triterpenes from Bergenia emeiensis

Abstract Bergenia emeiensis is a traditional folk medicine in China. Most studies are focusing on the bioactivity of bergenin, neglecting other compounds. Therefore, in this present work, the antioxidant, antibacterial and anticancer abilities of triterpenes from B. emeiensis rhizomes (TBE) were comprehensively evaluated. The results showed that TBE could well scavenge DPPH with a lower EC50 of 0.29 mg/mL and could improve the cell viability of CHO cells against H2O2 induced cell death. Additionally, TBE also enhanced the resistance of C. elegans under thermal stress, exhibiting a strong antioxidant potential in vivo. Moreover, TBE showed a certain antibacterial ability on five kind strains such as Pseudomonas aeruginosa while TBE could not significantly inhibit the growth of plant pathogenic fungi. Furthermore, TBE possessed an excellent suppression ability on the proliferation of cancer cells especially Hela and Hep G2 cells with an IC50 of 41.79 μg/mL and 48.62 μg/mL at 48 h, respectively. After fractionally extracted with petroleum ether, ethyl acetate and ethanol, ethanol phase (EP) contained the most triterpenes, followed by ethyl acetate phase (EAP) and petroleum ether phase (PEP). Besides, EP and EAP exhibited a strong antioxidant capacity and also inhibited the proliferation of Hela and Hep G2 cells with the effect of pro-oxidation by inducing a high level of ROS and decreasing mitochondrial membrane potential, thus causing oxidative stress then inducing cell apoptosis. Therefore, these outcomes indicated the triterpenes from B. emeiensis possessed a strong antioxidant ability and an anticancer effect, thus making B. emeiensis become a promising potential alternative in pharmacological field.

Design, synthesis, and in vitro/vivo anticancer activity of 4‐substituted 7‐(3‐fluoro‐4‐methoxybenzyl)‐7H‐pyrrolo[2,3‐d]pyrimidines

AbstractIn this paper, we report the design and synthesis of 4‐substituted 7‐(3‐fluoro‐4‐methoxybenzyl)‐7H‐pyrrolo[2,3‐d]pyrimidines of scaffold 6 as anticancer agents. A total of 19 derivatives of scaffold 6 bearing a C‐4 alkoxy, dialkylamino, alkyl, vinyl, or phenyl substituent were synthesized and evaluated. Among them, compound 6q having a C‐4 ethyl group and a benzylic methyl group showed the most potent in vitro anticancer activity, inhibiting the proliferation of Hela, MDA‐MB‐231, and MDA‐MB‐426 cancer cells at submicromolar concentrations (GI50: 0.11–0.58 μM). Compound 6q arrested the cell cycle of MDA‐MB‐231 at G2/M phase, and showed in vivo activity on nude mice bearing MDA‐MB‐231 xenografts. Compound 6q has served as an anticancer lead for further optimization.

Carbon Source Affects Synthesis, Structures, and Activities of Mycelial Polysaccharides from Medicinal Fungus Inonotus obliquus.

The effects of various carbon sources on mycelial growth and polysaccharide synthesis of the medicinal fungus Inonotus obliquus in liquid fermentation were investigated. After 12-d fermentation, mycelial biomass, polysaccharide yield, and polysaccharide content were significantly higher in Glc+Lac group (glucose and lactose used as combined carbon source) than in other groups. Crude polysaccharides (CIOPs) and the derivative neutral polysaccharides (NIOPs) were obtained from mycelia fermented using Glc, fructose (Fru), Lac, or Glc+Lac as carbon source. Molecular weights of four NIOPs (termed as NIOPG, NIOPF, NIOPL, and NIOPGL) were respectively 780.90, 1105.00, 25.32, and 10.28 kDa. Monosaccharide composition analyses revealed that NIOPs were composed of Glc, Man, and Gal at different molar ratios. The NIOPs were classified as α-type heteropolysaccharides with 1→2, 1→3, 1→4, 1→6 linkages in differing proportions. In in vitro cell proliferation assays, viability of RAW264.7 macrophages was more strongly enhanced by NIOPL or NIOPGL than by NIOPG or NIOPF, and proliferation of HeLa or S180 tumor cells was more strongly inhibited by NIOPG or NIOPGL than by NIOPF or NIOPL, indicating that immune-enhancing and anti-tumor activities of NIOPs were substantially affected by carbon source. qRT-PCR analysis revealed that expression levels of phosphoglucose isomerase (PGI) and UDP-Glc 4-epimerase (UGE), two key genes involved in polysaccharide synthesis, varied depending on carbon source. Our findings, taken together, clearly demonstrate that carbon source plays an essential role in determining structure and activities of I. obliquus polysaccharides by regulating expression of key genes in polysaccharide biosynthetic pathway.

EVALUATION OF IN VITRO ANTICANCER ACTIVITY OF AERIAL PARTS OF AVICENNIA ALBA PLANT METHANOLIC EXTRACT AGAINST HELA AND MCF-7 CELL LINES

Objective: The current study emphasizes the effects of stem and leaf methanolic extract of mangrove plant Avicennia alba on human tumor cell lines HeLa and MCF-7.
 Method: The collected mangrove plant sample was subjected to extraction with methanol and screened for anticancer activity according to 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The ability of the plant extract to inhibit the proliferation of HeLa and MCF-7 cell lines procured from NCCS Pune was compared parallel to inhibitory effect of standard drug Cisplatin. The spectrophotometric optical densities obtained were plotted on graph and consecutive data were obtained to depict the inhibitory effect and IC50 values. The histopathology studies were also done for a clear insight to understand the depth of inhibition microscopically.
 Results: The MTT assay performed illustrates the plant samples with different concentrations (10, 20, 25, 30, and 50 μg) showed significant inhibitory effect on comparison with the standard drug Cisplatin. The IC50 values and the inhibitory OD values elucidate effective projection of plant as a potential source of anticancer activity based on comparative study. The histopathology studies revealed an insight to a clearer picture of how the cells growth was controlled. It was found that the methanolic extract of A. alba exhibited more activity against HeLa cell lines than MCF-7 cell lines.
 Conclusion: The synergistic effect of various phytochemicals present in the methanolic plant extract played a significant role in establishing the plant as a significant anticancer source.

Antimicrobial, immunomodulatory and cytotoxic activities of green synthesized nanoparticles from Acacia honey and Calotropis procera.

Calotropis procera and Somra (Acacia) honey are used in traditional medicine. The benefits of mixing 20% Somra honey and C. procera leaf water extract (CPLWExt) were aimed to be studied. Honey/CPLWExt were utilized to produce silver nanoparticles (AgNPs) separately. AgNPs were characterized via UV/Vis and electron microscope scanning. Bio-molecules in CPLWExt/honey were investigated utilizing FT-IR spectroscopy. Biological activities of CPLWExt and honey were tested. The outcomes showed that CPLWExt and honey have numerous functional groups and could produce AgNPs. CPLWExt, CPLWExt + AgNPs, honey and honey + AgNPs hindered the growth of rat splenocytes, while CPLWExt + honey invigorated it. Antimicrobial power was found in CPLWExt and honey, which increased in the presence of AgNPs. Honey/honey + AgNPs suppressed the proliferation of HeLa and HepG2 cells. In conclusion, honey/CPLWExt could produce AgNPs and showed immunomodulatory and antibacterial power. Somra honey/honey + AgNPs have anticancer power. Somra honey + CPLWExt reflected a good immunostimulatory powers that can be nominated as an immunostimulant.

Overexpression of SOCS4 inhibits proliferation and migration of cervical cancer cells by regulating JAK1/STAT3 signaling pathway

Purpose: To delve into the related molecular mechanism of suppressor of cytokine signaling 4 (SOCS4) on cervical cancer cell proliferation and migration. Methods: Quantitative real-time polymerase chain reaction and western blot assays were employed to examine SOCS4 mRNA or protein expression in four human cervical cancer cell line (HeLa, SW-732, AV3, and CaSki) and normal cervical epithelium immortalized cell line (H8) MTT cell viability assays were applied to verify the cell proliferation of HeLa after overexpression of SOCS4. Wound scratch healing assays and transwell assays were applied to examine cell migration and invasion of HeLa after overexpression of SOCS4. Flow cytometry and western blot assays were applied to check the role of SOCS4 in the apoptosis of cervical cancer cells. The western blot assays were applied to examine the protein expression of JAK1, p-JAK1, STAT3, and p-STAT3 in HeLa after overexpression of SOCS4. Results: In this study, the results revealed that the mRNA and protein expression level of SOCS4 was lower in four human cervical cancer cell line than normal cervical epithelium immortalized cell line, respectively. Overexpression of SOCS4 inhibited the proliferation migration, and invasion of cervical cancer cells as well as promotes apoptosis of cervical cancer cells. Meanwhile, overexpression of SOCS4 in HeLa would inhibit phosphorylation of JAK1 and STAT3 protein. Conclusion: SOCS4 inhibited the proliferation and migration of cervical cancer cells by regulating the JAK1/STAT3 pathway.

Lappaol F, an anticancer agent, inhibits YAP via transcriptional and post-translational regulation

Context Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumour cell growth by inducing cell cycle arrest. However, its underlying anticancer mechanism remains unclear. Objective The effects of LAF on the Hippo-Yes-associated protein (YAP) signalling pathway, which plays an important role in cancer progression, were explored in this study. Materials and methods Cervical (HeLa), colorectal (SW480), breast (MDA-MB-231) and prostate (PC3) cancer cell lines were treated with LAF at different concentrations and different durations. BALB/c nude mice bearing colon xenografts were intravenously injected with vehicle, LAF (10 or 20 mg/kg) or paclitaxel (10 mg/kg) for 15 days. The expression and nuclear localisation of YAP were analysed using transcriptome sequencing, quantitative PCR, western blotting and immunofluorescence. Results LAF suppressed the proliferation of HeLa, MDA-MB-231, SW480 and PC3 cells (IC50 values of 41.5, 26.0, 45.3 and 42.9 μmol/L, respectively, at 72 h), and this was accompanied by significant downregulation in the expression of YAP and its downstream target genes at both the mRNA and protein levels. The expression of 14-3-3σ, a protein that causes YAP cytoplasmic retention and degradation, was remarkably increased, resulting in a decrease in YAP nuclear localisation. Knockdown of 14-3-3σ with small interfering RNA partially blocked LAF-induced YAP inhibition and anti-proliferation effects. In colon xenografts, treatment with LAF led to reduced YAP expression, increased tumour cell apoptosis and tumour growth inhibition. Conclusion LAF was shown to be an inhibitor of YAP. It exerts anticancer activity by inhibiting YAP at the transcriptional and post-translational levels.

Identification of Hub Genes as Potential Prognostic Biomarkers in Cervical Cancer Using Comprehensive Bioinformatics Analysis and Validation Studies.

BackgroundCervical cancer belongs to one of the most common female cancers; yet, the exact underlying mechanisms are still elusive. Recently, microarray and sequencing technologies have been widely used for screening biomarkers and molecular mechanism discovery in cancer studies. In this study, we aimed to analyse the microarray datasets using comprehensive bioinformatics tools and identified novel biomarkers associated with the prognosis of patients with cervical cancer.MethodsThe differentially expressed genes (DEGs) from Gene Expression Omnibus (GEO) datasets including GSE138080, GSE113942 and GSE63514 were analysed using GEO2R tool. The functional enrichment analysis was performed using g:Profiler tool. The protein–protein interaction (PPI) network construction and hub genes identification were performed using the STRING database and Cytoscape software, respectively. The hub genes were subjected to expression and survival analysis in the cervical cancer. The EdU incorporation and Cell Counting Kit-8 assays were performed to evaluate the effects of hub gene knockdown on the proliferation of cervical cancer cells.ResultsA total of 89 overlapping DEGs (63 up-regulated and 26 down-regulated genes) were identified in the microarray datasets. The functional enrichment analysis indicated that the overlapping DEGs were mainly associated with “DNA replication” and “cell cycle”. Furthermore, the PPI network analysis revealed that the network contains 87 nodes and 309 edges. Sub-module analysis using the Molecular Complex Detection tool identified 21 hub genes from the PPI network. The expression levels of the 21 hub genes were all up-regulated in the cervical cancer tissues when compared to normal cervical tissues as analysed by GEPIA tool. The survival analysis showed that the low expression of cell division cycle 45 (CDC45), GINS complex subunit 2 (GINS2), minichromosome maintenance complex component 2 (MCM2) and proliferating cell nuclear antigen (PCNA) was significantly correlated with the shorter overall survival of patients with cervical cancer. Moreover, the protein expression levels of GINS2, MCM2 and PCNA, but not CDC45, were significantly up-regulated in the cervical cancer tissues when compared to normal cervical tissues. Finally, knockdown of MCM2 significantly suppressed the proliferation of HeLa and SiHa cells.ConclusionIn conclusion, we screened a total of 89 overlapping DEGs from the GEO datasets, and further analysis identified four hub genes (CDC45, GINS2, MCM2 and PCNA) that were likely associated with the prognosis of patients with cervical cancer. MCM2 knockdown repressed the cervical cancer cell proliferation. The current findings may provide novel insights into understanding the pathophysiology of cervical cancer and develop therapeutic targets for patients with cervical cancer.

Nanoencapsulation of Andrographolide Rich Extract for the Inhibition of Cervical and Neuroblastoma Cancer Cells.

Andrographis paniculata is traditionally used for many diseases and scientifically proven for anti-cancer property. Andrographolide which is the marker compound is believed to be the main contributor to the pharmacological activities. The poor solubility and bioavailability of this diterpenoid lactone could be overcome by nanoencapsulation. Reflux extraction, and followed by successive Soxhlet fractionation were used to obtain andrographolide rich extract from the herb. Spontaneous emulsion solvent diffusion was used to nanoencapsulate andrographolide using poly(lactic-co-glycolic acid) with 1% polyvinyl alcohol as emulsifier. Nanospheres loaded with andrographolide was found to have the particle size, 163 nm; polydispersity index, 0.26 and zeta potential, - 57.85 mV. The encapsulation efficiency and in vitro drug release were 80.0% and 84.2%, respectively. The andrographolide nanoparticles could inhibit the proliferation of cervical and neuroblastoma cells with no adverse effect on normal human skin cells. Andrographolide rich extract loaded nanoparticles could inhibit the proliferation of HeLa and SH-SY5Y cells, mainly through Bax-induced apoptosis. The result was consistent with the low expression of anti-apoptotic genes (Bcl-2 and Bcl-xL) and prognostic factor (Ki-67). The tumour size of HeLa bearing mice was significantly reduced (73%) after treated with andrographolide rich nanoparticles (10 mg/kg body weight) for a month.

Biological function and molecular properties of Pyrenaican SF-1 as biological macromolecule extracted from Daldinia pyrenaica

Molecular properties and biological functions of Pyrenaican SF-1 as a novel biological macromolecule extracted from a fungal isolate were studied. The isolate was identified as Daldinia pyrenaica on the basis of 5.8S rDNA sequencing. Pyrenaican SF-1 was obtained from the culture filtrate of the fungal isolate. The partial characterization of biochemical structure of Pyrenaican SF-1 was conducted. The fungal extract was also tested for the treatment of AGS, MDA and HeLa cell lines to assess cells proliferation, cells cycle and apoptosis. Furthermore, Pyrenaican SF-1 extract was tested for its antibacterial and antioxidant activity. Initial chemical analysis revealed that Pyrenaican SF-1 extract was composed of various monosaccharides such as d-glucose, D- mannitol, D-arabinose and β-D-ribopyranose. In vitro study indicated that Pyrenaican SF-1 could effectively elevate percentage of apoptosis and necrosis of cancer cells and block cell cycle phase of the control group. The fungal extract could inhibit proliferation of Hela and MDA cell up to 67% and 56%, respectively. Moreover, Pyrenaican SF-1 represented a strong antioxidant activity compared to that one obtained from vitamin C. On the other hand, Pyrenaican SF-1 exhibited growth inhibitory effects against different Gram-negative and Gram-positive bacterial strains. Pyrenaican SF-1 can be considered as a bioactive macromolecule with promising application in pharmaceutical and medical sectors.

Potential Antimicrobial and Anticancer Activities of an Ethanol Extract from Bouea macrophylla.

Bouea macrophylla is a tree widely grown throughout South East Asia. It is used in folk medicine for the treatment of various illnesses. The present study aimed to identify the chemical constituents and to test the antimicrobial and anticancer activities of an ethanol extract from B. macrophylla leaves. The extract exhibited excellent antibacterial properties against 9 out of 10 target microorganisms. including four Gram-negative bacteria (Escherichia coli, Shigella flexneri, Vibrio cholera, and Pseudomonas aeruginosa) and four Gram-positive bacteria (Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, and Bacillus cereus), as well as a fungus (Candida albicans). In addition, the extract was also tested on HeLa and human colorectal carcinoma (HCT116) cells to evaluate its cytostatic effects. The ethanol extract was able to inhibit the proliferation of HeLa and HCT116 cells, showing IC50 = 24 ± 0.8 and 28 ± 0.9 µg/mL, respectively, whereas the IC50 values of doxorubicin (standard) were 13.6 ± 1.3 and 15.8 ± 1.1 µg/mL respectively. Also, we identified various bioactive compounds in the extract such as polyphenols, flavonoids, caryophyllene, phytol, and trans-geranylgeraniol by GC-MS, which could contribute to the extract’s biological activities. Therefore, our findings strongly indicate that the constituents of the B. macrophylla ethanol extract could be active against the tested bacteria and fungi as well as cancer cells. Further investigation is needed to understand the mechanisms mediating the antimicrobial and anticancer effects and identify signaling pathways that could be targeted for therapeutic application.

Cucurbitacin IIb, a steroidal triterpene from Ibervillea sonorae induces antiproliferative and apoptotic effects on cervical and lung cancer cells

Chemical studies on Ibervillea sonorae (S. Watson) Greene root led to isolation and chemical characterization of diverse cucurbitacin triterpenoid compounds such as kinoin A, B, C, and their glucosides. In previous studies, we demonstrated that kinoin A inhibits the cell proliferation on diverse cell line and induce apoptosis in HeLa cells. Therefore, the study of the isolated compounds from the extracts continued to be necessary. The objective of the present work was to isolate and chemically characterize the active compounds of the methanolic extract of the roots of I. sonorae and to evaluate their antiproliferative activity and induction of apoptosis. By chromatographic column separation and using NMR spectroscopy experiments, cucurbitacin IIb (CIIb), known as 23,24-dihydrocucurbitacin F or hemslecin B, was isolated and identified for the first time as a chemical constituent of the crude methanolic extract of this plant. The antiproliferative activity of CIIb was evaluated by MTT assay, and the apoptosis induction capacity was monitored by annexin V-FITC/propidium iodide using flow cytometry. CIIb showed a pronounced effect on the proliferation of HeLa and A549 tumor cells, with IC50 of 7.3 and 7.8 µM, respectively, but was less effective against L929 non-cancerous murine cell line. Apoptosis induction capacity of CIIb on HeLa and A549 was monitored by annexin V-FITC/propidium iodide using flow cytometry. Exposure of HeLa and A549 with CIIb (8 µM) for 24 h increased 56.9 and 52.3% respectively of the total apoptosis compared to the negative control (p < 0.005). CIIb, isolated for the first time from I. sonorae, showed antiproliferative activity against HeLa and A549 cell lines by inducing cell death by apoptosis.

MiR-21 Inhibits Cell Proliferation and Apoptosis Through Regulating the Phosphatase and Tensin Homolog/Phosphoinositide 3-Kinase/Akt Signaling Pathway in Cervical Cancer Cells

A variety of miRNAs regulate cellular physiology and tumor cells. miR-21 regulates tumorigenesis though the modulating cell apoptosis, migration and invasiveness via activating PTEN/PI3K signaling pathway. This study aimed to assess miR-21’s effect on cervical cancer cells and the underlying mechanisms. HeLa were cultured in DMEM medium. Western blotting was to measure bcl-2, bax, p-Akt, PTEN protein level. Annexin V-FITC was measured to analyze the samples by using confocal laser scanning microscopy. Our result showed that miR-21 significantly induced the cell apoptosis of HeLa via decreasing the protein expression of bcl-2. miR-21 markedly inhibited PI3K/Akt signaling, increased PTEN level, induced cancer cell apoptosis and retarded the tumor angiogenesis and proliferation. miR-21 could regulate the proliferation of HeLa via upregulation of PTEN and downregulation of PI3K/Akt pathway, which provides a novel therapeutic insight for the therapy of cervical cancer.

Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis.

Background: Sesamin is a major bioactive compound in sesame seeds and has various biological properties, including anti-inflammatory and anticancer activities. Here, we explored whether sesamin activates p53, which is widely inhibited in cervical cancer cells, thereby inducing p53-mediated apoptosis.Methods: Human HeLa and SiHa cervical cancer cells and normal Hs68 dermal cells were used as cell models. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by the CCK-8 assay and flow cytometry using PI/Annexin V staining, respectively. Protein expression and phosphorylation were determined using western blotting. The involvement of p53 in the apoptotic cascade was assessed by a specific inhibitor.Results: Sesamin (75 and 150 μM) clearly inhibited SiHa and HeLa cell proliferation in a dose-dependent fashion, but did not affect the proliferation of Hs68 cells. Meanwhile, sesamin increased the sub-G1 phase ratio and apoptosis, up to approximately 38.5% and 37.8%, respectively. Furthermore, sesamin induced p53 phosphorylation at serine-46 and serine-15 and upregulated the levels of PUMA, Bax, and PTEN, while inhibiting AKT phosphorylation at serine-473. Inhibition of p53 by pifithrin-α significantly reduced the levels of PUMA, Bax, and PTEN but restored AKT phosphorylation in SiHa cells exposed to sesamin. Pifithrin-α also reduced apoptosis and restored the proliferation of HeLa and SiHa cells exposed to sesamin.Conclusions: These findings indicate that sesamin inhibits cervical cancer cell proliferation, and its mechanism may be attributed to the induction of p53/PTEN-mediated apoptosis. This suggests that sesamin might be useful as an adjuvant in promoting anti-cervical cancer treatments.

Optimization of Cinnamon (Cinnamomum zeylanicum Blume) Essential Oil Extraction: Evaluation of Antioxidant and Antiproliferative Effects.

Having high cytotoxicity cell line effect, Cinnamomum zeylanicum Blume essential oil offers a novel approach to the chemotherapy treatment. In order to enhance its quantity/purity, the experimental conditions to produce essential oil should be more exploited. Steam distillation was used to isolate essential oil, and its conditions' optimization was carried out with the surface-response methodology. The maximum amount (2.6 g/100 g d.b.) was obtained under minimum condensation water flow (0.8 mL/min), a sample size of 6.5 cm, a saline solution concentration of 262.5 g/L, and five washings. The produced essential oil contains >77% of polyphenols. In vitro cytotoxicity was examined using an MTT assay against HeLa and Raji cell lines. The essential oil's capability to inhibit the proliferation of HeLa and Raji cell lines was studied under some conditions presenting IC50 values of 0.13 and 0.57 μg/mL, respectively. The essential oil was evaluated for its potential as an antioxidant by using in vitro models, such as phosphomolybdenum, DPPH, and H2O2 methods, in comparison with the synthetic antioxidant BHT (butylated hydroxytoluene) and ascorbic acid (vitamin C) as positive controls. The ammonium phosphomolybdate potency in the present study is of the order of 108.75 ± 32.63 mg of essential oil/equivalent to 1 mg of vitamin C in terms of antioxidant power, and the antioxidant activity of DPPH-H2O2 was 21.3% and 55.2%, respectively. The Cinnamomum zeylanicum Blume essential oil (CEO) covers important antioxidant and antiproliferative effects. This can be attributed to the presence of few minor and major phenolic compounds.