scholarly journals Cytostatic and Antiproliferative Activities of F5 Fraction of Crinum amabile Leaf Chloroform Extract Showed Its Potential as Cancer Chemotherapeutic Agent

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Chung Pin Lim ◽  
Mun Fei Yam ◽  
Mohd. Zaini Asmawi ◽  
Voon Kin Chin ◽  
Nurul Hayah Khairuddin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dna Fragmentation ◽  
Cell Apoptosis ◽  
Anticancer Agent ◽  
Chemotherapeutic Agent ◽  
Annexin V ◽  
Chloroform Extract ◽  
Potential Source ◽  
Apoptotic Effect ◽  
Mcf 7

Medicinal plants have been considered as promising sources of drugs in treating various cancers. Crinum amabile (C. amabile), a plant species from the Amaryllidaceae family, is claimed to be a potential source for cancer chemotherapeutic compounds. Here, we aimed to investigate the potential of C. amabile as an anticancer agent. Dried leaves of C. amabile were serially extracted and our findings showed that chloroform extract (CE) was shown to exhibit cytotoxic effect against all cancer cell lines used. This active extract was further fractionated in which F5 fraction was shown to possess the highest cytotoxicity among all fractions. F5 fraction was then tested in-depth through Annexin V/FITC apoptosis and DNA fragmentation assays to determine its apoptotic effect on MCF-7 cells. Results revealed that F5 fraction only showed induction of cell apoptosis starting at 72-hour treatment while DNA fragmentation was not detected at any of the concentrations and treatment periods tested. Meanwhile, cell proliferation assay revealed that F5 fraction was able to inhibit normal cell proliferation as well as VEGF-induced cell proliferation of normal endothelial cell (HUVECs). In conclusion, F5 fraction from C. amabile leaf CE was able to exhibit cytostatic effect through antiproliferation activity rather than induction of cell apoptosis and therefore has the potential to be further investigated as an anticancer agent.

Effects of Simvastatin on Breast Carcinoma Cell Proliferation and Apoptosis via Transforming Growth Factor-β1/Smad3 Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 1673-1682
Author(s):  
Feng Wang ◽  
Gengbao Qu ◽  
Baokai Wang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Breast Carcinoma ◽  
Protein Expression ◽  
Breast Cancer Cell ◽  
Cell Apoptosis ◽  
Carcinoma Cell ◽  
Proliferation And Apoptosis ◽  
Smad3 Protein ◽  
Mcf 7

Objective: To investigate the function and causative role of simvastatin (Sim) in breast carcinoma cell apoptosis as well as proliferation. Methods: 20 breast carcinoma patients requiring surgery were treated with Sim (20 days, 30 mg), and samples of pre-treatment (pre) and post-treatment (post) were acquired. We detected tissue cell proliferation and apoptosis changes and used functional experiments to detect cell proliferation and apoptosis changes after treating not only estrogen receptor (ER)-positive (MCF-7) but also ER-negative cells (MDA-MB-231) with Sim or TGF-β1. Detection of p-Smad3 and total Smad3 protein expression changes was conducted, and we finally used in vivo experiments to assess the influence of Sim on breast tumor growth and drug safety. Results: Immunohistochemistry and TUNEL staining results showed that after treatment with Sim, breast carcinoma cell proliferation decreased and apoptosis increased. Functional experiments results showed that Sim notedly promoted the MDA-MB-231 and MCF-7 cell apoptosis, inhibiting migration, proliferation and epithelial mesenchymal transition. Moreover, TGF-β1 protein expression was strikingly lower in Sim group than that in DMSO group. When TGF-β1 and Sim were combined to use, the inhibitory ability of Sim on breast cancer cell proliferation markedly increased and the capability of TGF-β1 protein inducing p-Smad3 protein increased. In addition, after Sim treatment in mice, the tumor volume became smaller, the pathological changes weakened, and there was no significant effect on liver function and kidney function. Conclusion: Sim participates in breast cancer cell apoptosis and proliferation via regulating TGF-β1/Smad3 signal pathway.

scholarly journals Long non-coding RNA LBX2-AS1 enhances glioma proliferation through downregulating microRNA-491-5p

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qunbang Chen ◽  
Jian Gao ◽  
Yingjia Zhao ◽  
Ruizhe Hou
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Glioma Cells ◽  
Annexin V ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Normal Brain ◽  
Lower Grade ◽  
Rt Pcr ◽  
Glioma Cell Proliferation

Abstract Background Dysregulation of lncRNAs is frequent in glioma and has emerged as an important mechanism involved in tumorigenesis. Previous analysis of Chinese Glioma Genome Atlas (CGGA) database indicated that LBX2-AS1 expression is one of differentially expression lncRNA between lower grade glioma (LGG) (grade II and III) and glioblastoma multiforme (GBM). However, the function and mechanism of LBX2-AS1 in glioma has not been evaluated yet. Methods Here, we analyzed the expression of LBX2-AS1 in GTEx data (normal brain), TCGA-LGG and TCGA-GBM. RT-PCR was performed to detect LBX2-AS1 in surgery obtained normal brain and glioma. CCK-8 kit and Annexin V-FITC-PI Apoptosis Detection Kit were used to study the function of LBX2-AS1 on glioma proliferation and apoptosis. Bioinformatic analysis, RNA immunoprecipitation, RT-PCR, western blotting and dual luciferase reporter assay were carried out to investigate the target miRNA of LBX2-AS1. The discovered mechanism was validated by the rescue assay. Results Following study of GTEx and TCGA data, LBX2-AS1 was significantly elevated in glioma compared with normal brain and in GBM compared with LGG. Higher expression of LBX2-AS1 was associated with poor prognosis of patients with glioma. Expression of LBX2-AS1 was positively correlated with pathology classification of glioma. Knockdown of LBX2-AS1 inhibited cell proliferation and induced cell apoptosis in glioma. LBX2-AS1 have complimentary binding site for tumor suppressor miR-491-5p and we showed that LBX2-AS1 sponged miR-491-5p to upregulate TRIM28 expression in glioma cells. TRIM28 overexpression attenuated the effect of LBX2-AS1 knockdown on glioma cells. Conclusions In conclusion, LBX2-AS1 was an increased lncRNA in glioma. Mechanistically, LBX2-AS1 promoted glioma cell proliferation and resistance to cell apoptosis via sponging miR-491-5p.

scholarly journals Dihydrochalcone Derivative Induces Breast Cancer Cell Apoptosis via Intrinsic, Extrinsic, and ER Stress Pathways but Abolishes EGFR/MAPK Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Wasitta Rachakhom ◽  
Patompong Khaw-on ◽  
Wilart Pompimon ◽  
Ratana Banjerdpongchai
Keyword(s):  
Breast Cancer ◽  
Er Stress ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Annexin V ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Induced Apoptosis ◽  
Mcf 7

Dihydrochalcone derivatives are active compounds that have been purified from the Thai medicinal plant Cyathostemma argenteum. The objectives of this study were to investigate the effects of two dihydrochalcone derivatives on human breast cancer MDA-MB-231 and MCF-7 cell proliferation and to study the relevant mechanisms involved. The two dihydrochalcone derivatives are 4′,6′-dihydroxy-2′,4-dimethoxy-5′-(2″-hydroxybenzyl)dihydrochalcone (compound 1) and calomelanone (2′,6′-dihydroxy-4,4′-dimethoxydihydrochalcone, compound 2), both of which induced cytotoxicity toward both cell lines in a dose-dependent manner by using MTT assay. Treatment with both derivatives induced apoptosis as determined by annexin V-FITC/propidium iodide employing flow cytometry. The reduction of mitochondrial transmembrane potential (staining with 3,3′-dihexyloxacarbocyanine iodide, DiOC6, employing a flow cytometer) was established in the compound 1-treated cells. Compound 1 induced caspase-3, caspase-8, and caspase-9 activities in both cell lines, as has been determined by specific colorimetric substrates and a spectrophotometric microplate reader which indicated the involvement of both the extrinsic and intrinsic pathways. Calcium ion levels in mitochondrial and cytosolic compartments increased in compound 1-treated cells as detected by Rhod-2AM and Fluo-3AM intensity, respectively, indicating the involvement of the endoplasmic reticulum (ER) stress pathway. Compound 1 induced cell cycle arrest via enhanced atm and atr expressions and by upregulating proapoptotic proteins, namely, Bim, Bad, and tBid. Moreover, compound 1 significantly inhibited the EGFR/MAPK signaling pathway. In conclusion, compound 1 induced MDA-MB-231 and MCF-7 cell apoptosis via intrinsic, extrinsic, and ER stress pathways, whereas it ameliorated the EGFR/MAPK pathway in the MCF-7 cell line. Consequently, it is believed that compound 1 could be effectively developed for cancer treatments.

Lenti-shRNA-mediated FAM54A knockdown suppresses the proliferation and induces apoptosis of human Burkitt lymphoma cells

2020 ◽  
Author(s):  
Guang Yang ◽  
Hua Xiao Wang ◽  
Bin Yan ◽  
Yan Chun Xu ◽  
Yi Ru Zheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Line ◽  
Burkitt Lymphoma ◽  
Cell Apoptosis ◽  
Annexin V ◽  
Negative Control ◽  
Namalwa Cell ◽  
Control Shrna ◽  
Burkitt Lymphoma Cell Line

Abstract Background Burkitt lymphoma is a kind of non-Hodgkin B-cell-derived malignancy, derived from germinal center B cells. FAM54A has been proved to be involved in various physiological and pathological processes of cancers, but the biological function of FAM54A in Burkitt lymphoma remains unclear. Thus, the aim of our research was to elucidate the roles of FAM54A in proliferation, apoptosis and cell cycle of Burkitt lymphoma.Methods Burkitt lymphoma cell line (Namalwa) was chosen to perform the following experiments. FAM54A-shRNA and negative control-shRNA lentivirus that were synthesized, respectively by Qiagen were used to transfect targeted cells in order to knockdown FAM54A or as negative control. Then, cell proliferation, cell cycle and cell apoptosis were detected by using MTS assay, propidium iodide staining and Annexin V-APC staining, respectively.Results Our results showed that high expression of FAM54A protein was found in Namalwa cell line. Furthermore, MTS analysis exhibited that knockdown of FAM54A obviously inhibited cell proliferation in Namalwa cells. What’s more, cell cycle analysis showed that knockdown of FAM54A induced Namalwa cell apoptosis and arrested cell cycle in G2/M phase.Conclusions These findings suggest that FAM54A is essential for Namalwa cell proliferation and may be a potential therapeutic target for the treatment of Burkitt lymphoma.

scholarly journals Rosemary oil nano-emulsion potentiates the apoptotic effect of mitomycin C on cancer cells in vitro

Pharmacia ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 201-209
Author(s):  
Waad Al-otaibi
Keyword(s):  
Mitomycin C ◽  
Anticancer Agent ◽  
Combination Index ◽  
Fluorescent Microscopy ◽  
Low Concentrations ◽  
Apoptotic Effect ◽  
Rosemary Oil ◽  
Nano Emulsion ◽  
Mcf 7

Purpose: To formulate nano-emulsified rosemary oil (REO/NE) and determine its effect on the anticancer agent, mitomycin C (MC) when used as a carrier for the drug. Methods: The droplet size of REO/NE was markedly enlarged when mixed with MC. The cytotoxicity of the formulations on HeLa and MCF-7 cells was determined using MTT assay. The combination index (CI) values were estimated with CompuSyn software, while apoptosis was determined using DAPI fluorescent dye. Results: Treatment of MCF-7 cells and HeLa cells with REO/NE (1% v:v and 1.33% v:v, respectively) reduced the IC50 of MC 33 and 15 folds, respectively. Under fluorescent microscopy, cells treated with REO/NE+MC had more marked reduction of the nuclear area than MC-treated cells. Conclusion: These results indicate that REO/NE is an efficient carrier for MC since it enhanced MC delivery and increased its effect on the cells through the induction of apoptosis at low concentrations of MC.

scholarly journals Gambogic Acid Lysinate Induces Apoptosis in Breast Cancer MCF-7 Cells by Increasing Reactive Oxygen Species

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yong-Zhan Zhen ◽  
Ya-Jun Lin ◽  
Kai-Ji Li ◽  
Xiao-Shan Yang ◽  
Yu-Fang Zhao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Human Cancer ◽  
Signal Pathway ◽  
Gambogic Acid ◽  
Oxygen Species ◽  
Human Cancer Cells ◽  
Intracellular Ros ◽  
Mcf 7

Gambogic acid (GA) inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of GA is limited.Objectives.To investigate the antitumor activity of gambogic acid lysinate (GAL) and its mechanism.Methods.Inhibition of cell proliferation was determined by MTT assay; intracellular ROS level was detected by staining cells with DCFH-DA; cell apoptosis was determined by flow cytometer and the mechanism of GAL was investigated by Western blot.Results.GAL inhibited the proliferation of MCF-7 cells with IC50values 1.46 μmol/L comparable with GA (IC50, 1.16 μmol/L). GAL promoted the production of ROS; however NAC could remove ROS and block the effect of GAL. GAL inhibited the expression of SIRT1 but increased the phosphorylation of FOXO3a and the expression of p27Kip1. At knockdown of FOXO3a, cell apoptosis induced by GAL can be partly blocked. In addition it also enhanced the cleavage of caspase-3.Conclusions.GAL inhibited MCF-7 cell proliferation and induced MCF-7 cell apoptosis by increasing ROS level which could induce cell apoptosis by both SIRT1/FOXO3a/p27Kip1 and caspase-3 signal pathway. These results suggested that GAL might be useful as a modulation agent in cancer chemotherapy.

scholarly journals Involvement of theca cells and steroids in the regulation of granulosa cell apoptosis in rabbit preovulatory follicles

Reproduction ◽  
2003 ◽  
pp. 709-716 ◽  
Author(s):  
G Maillet ◽  
A Benhaim ◽  
H Mittre ◽  
C Feral
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Apoptosis ◽  
Annexin V ◽  
Rapid Loss ◽  
Theca Cells ◽  
Preovulatory Follicles ◽  
Apoptotic Effect

Follicular atresia is characterized by a rapid loss of granulosa cells and, to a lesser extent, theca cells, via apoptosis. The aim of this study was to investigate the possible involvement of theca cell secretions in the regulation of apoptosis of rabbit granulosa cells. The annexin-V binding method based on externalization of phosphatidylserine to the outer layer of plasma membrane during apoptosis was used to detect apoptotic granulosa cells in flow cytometry. Regulation of apoptosis of granulosa cells was studied in three different culture systems: (i) isolated cultured granulosa cells, (ii) granulosa cells obtained from cultured preovulatory follicles and (iii) granulosa cells co-cultured with theca cells. The results of this study indicate that: (i) the rate of apoptosis of granulosa cells was significantly reduced when granulosa cells were co-cultured with theca cells or obtained from cultured preovulatory follicles in comparison with isolated cultured granulosa cells; (ii) FSH exerts its anti-apoptotic effect only on granulosa cells issued from cultured preovulatory follicles; (iii) ovarian steroids do not affect the percentage of isolated apoptotic granulosa cells; and (iv) the occurrence of an apoptotic process in rabbit theca cells could be upregulated in vitro by hCG and an analogue of the gonadotrophin second messenger cAMP. The results of this study indicate that in rabbits (i) steroids were ineffective in vitro in protecting isolated granulosa cells against apoptosis in comparison with observations in vivo in rats, and (ii) the presence of theca cells was efficient to reduce granulosa cell apoptosis but not sufficient to allow the anti-apoptotic effect of gonadotrophins observed in cultured follicles.

scholarly journals Antiproliferative and Antiangiogenic Properties of New VEGFR-2-targeting 2-thioxobenzo[g]quinazoline Derivatives (In Vitro)

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5944
Author(s):  
Hatem A. Abuelizz ◽  
Mohamed Marzouk ◽  
Ahmed H. Bakheit ◽  
Hanem M. Awad ◽  
Maha M. Soltan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Dna Fragmentation ◽  
Cancer Cell ◽  
Catalytic Domain ◽  
Annexin V ◽  
Docking Study ◽  
Reference Drug ◽  
Mcf 7

A series of 3-ethyl(methyl)-2-thioxo-2,3-dihydrobenzo[g]quinazolines (1–17) were synthesized, characterized, and evaluated in vitro for their antiangiogenesis VEGFR-2-targeting, antiproliferative, and antiapoptotic activities against breast MCF-7 and liver HepG2 cells. Flow cytometry was used to determine cancer-cell cycle distributions, and apoptosis was detected using annexin-V-FITC (V) and propidium iodide (PI) dyes. Fluorescence microscopy, in combination with Hoechst staining was used to detect DNA fragmentation. Most of the tested benzo[g]quinazolines demonstrated promising activity (IC50 = 8.8 ± 0.5–10.9 ± 0.9 μM) and (IC50 = 26.0 ± 2.5–40.4 ± 4.1 μM) against MCF-7 and HepG2, respectively. Doxorubicin was used as a reference drug. Compounds 13–15 showed the highest activity against both cancer cell lines. Differential effects were detected by cell-cycle analysis, indicating similarities in the actions of 13 and 14 against both MCF7 and HepG2, involving the targeting of G1 and S phases, respectively. Compound 15 showed similar indices against both cells, indicating that its cytotoxicity toward the examined cancer cells could be unselective. Interestingly, 14 and 15 showed the highest apoptosis (30.76% and 25.30%, respectively) against MCF-7. The DNA fragmentation results agreed well with the apoptosis detected by flow cytometry. In terms of antiangiogenesis activity, as derived from VEGFR-2 inhibition, 13 and 15 were comparable to sorafenib and effected 1.5- and 1.4-fold inhibition relative to the standard sorafenib. A docking study was conducted to investigate the interaction between the synthesized benzo[g]quinazolines and the ATP-binding site within the catalytic domain of VEGFR-2.

scholarly journals Resistin is a survival factor for porcine ovarian follicular cells

Reproduction ◽  
2015 ◽  
Vol 150 (4) ◽  
pp. 343-355 ◽  
Author(s):  
Agnieszka Rak ◽  
Eliza Drwal ◽  
Anna Wróbel ◽  
Ewa Łucja Gregoraszczuk
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Western Blot ◽  
Dna Fragmentation ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Inhibitory Effect ◽  
Ovarian Cell ◽  
Proliferation And Apoptosis ◽  
Mrna And Protein Expression

Previously, we demonstrated the expression of resistin in the porcine ovary, the regulation of its expression and its direct effect on ovarian steroidogenesis. The objective of this study was to examine the effect of resistin on cell proliferation and apoptosis in a co-culture model of porcine granulosa and theca cells. First, we analysed the effect of resistin at 1 and 10 ng/ml alone or in combination with FSH- and IGF1 on ovarian cell proliferation with an alamarBlue assay and protein expression of cyclins A and B using western blot. Next, the mRNA and protein expression of selected pro-apoptotic and pro-survival regulators of cell apoptosis, caspase-9, -8 and -3 activity and DNA fragmentation using real time PCR, western blot, fluorescent assay and an ELISA kit, respectively, were analysed after resistin treatment. Furthermore, we determined the effect of resistin on the protein expression of ERK1/2, Stat and Akt kinase. Using specific inhibitors of these kinases, we also checked caspase-3 activity and protein expression. We found that resistin, at both doses, has no effect on cell proliferation. The results showed that resistin decreased pro-apoptotic genes, which was confirmed on protein expression of selected factors. We demonstrate an inhibitory effect of resistin on caspase activity and DNA fragmentation. Finally, resistin stimulated phosphorylation of the ERK1/2, Stat and Akt and kinases inhibitors reversed resistin action on caspase-3 activity and protein expression to control. All of these results showed that resistin has an inhibitory effect on porcine ovarian cell apoptosis by activation of the MAPK/ERK, JAK/Stat and Akt/PI3 kinase signalling pathways.

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