Inhibition of Morusin From Mulberry Branches As An Agro-Waste to MDA-MB-453 and HCT116 Cancer Cells By Inducing Cell Apoptosis and Disturbing The Cell Cycle

2021 ◽  
Author(s):  
Zhi-Hao Zhong ◽  
Yu-Qing Zhang
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Epithelial Mesenchymal Transition ◽  
Dependent Manner ◽  
High Concentration ◽  
Mesenchymal Transition ◽  
Silk Industry ◽  
Cancer Migration

Abstract Mulberry tree branches are one of the largest agro-wastes produced in silk industry. How to make full use of this waste has always been one of the most important issues for the silk industry and even the entire biological industry. The paper has first reported that the inhibition of morusin recovered from mulberry branch barks, a prenylated flavonoid, on 20 kinds of tumour cells, of which the IC50 values of the 80% cells reaches about 15 µM. Second, effects on the proliferation, invasion and apoptosis of two cancer cells were investigated in detail. The experimental results showed that the apoptotic ratio of the high concentration was 77.73% in MDA-MB-453 cells. Western blotting displayed that morusin upregulated E-cadherin and downregulated vimentin and N-cadherin in a dose-dependent manner, and thus reversed epithelial-mesenchymal transition. It could upregulate cleaved Caspase-3 and Bax and downregulate Caspase-3 and Bcl-2, which indicate that the cell apoptosis is induced by morusin. These cancer cells, MDA-MB-453, were blocked in G2 phase, and HCT116 were arrested in S phase when treated with morusin, which is possible that the cell cycle is disturbed. Therefore, morusin could inhibit cancer migration and growth and promote cancer cell apoptosis.

scholarly journals LncRNA HOXB-AS3 Promotes Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Gallbladder Cancer Cells by Activating the MEK/ERK Pathway

2022 ◽  
Author(s):  
Jiayan Wu ◽  
Hongquan Zhu ◽  
Jiandong Yu ◽  
Zhiping Chen ◽  
Zeyu Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Migration ◽  
Cell Viability ◽  
Gallbladder Cancer ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Migration Ability ◽  
Mesenchymal Transition

Abstract OBJECTIVE: Long non-coding RNA HOXB-AS3 has been implicated in tumor progression in a variety of carcinomas. However, its biological role in gallbladder cancer (GBC) is unknown. The biological function and underlying mechanism of the lncRNA HOXB-AS3 for GBC were investigated in this study.MATERIALS AND METHODS: To investigate the function of lncRNA HOXB-AS3 in GBC, the level of lncRNA HOXB-AS3 in GBC cells was detected by quantitative reverse-transcription polymerase chain reaction. The cell viability was tested by cell counting kit-8 assay and colony formation assay. Flow cytometry was performed to investigate cell apoptosis and cell cycle. In addition, cell migration ability was assessed by wound healing assay and cell invasion ability by transwell invasion assay. RESULTS: It was found that HOXB-AS3 was obviously elevated in GBC tissues and cells. However, inhibition of HOXB-AS3 could depress NOZ and GBC-SD cell viability as well as induce cell apoptosis. Also, the gallbladder cancer cell cycle was blocked in the G1 phase. Meanwhile, NOZ and GBC-SD cell migration, invasion, and epithelial-mesenchymal transition were obviously suppressed by knockdown of HOXB-AS3. What is more, we found that HOXB-AS3 might promote gallbladder progress by activating the MEK/ERK pathway.CONCLUSION: The results show that lncRNA HOXB-AS3 serves as a key regulator in GBC progression, which provides a new treatment strategy for GBC.

scholarly journals Anticancer and apoptosis-inducing effects of curcumin against gall bladder carcinoma

2018 ◽  
Vol 9 (1) ◽  
pp. 68 ◽  
Author(s):  
Pratibha Pandey ◽  
Uzma Sayyed ◽  
Rohit Tiwari ◽  
Neelam Pathak ◽  
Mohammad Haris Siddiqui ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Gall Bladder ◽  
Cancer Cells ◽  
Bladder Carcinoma ◽  
Caspase 3 ◽  
Gall Bladder Cancer ◽  
Dependent Manner ◽  
Gall Bladder Carcinoma ◽  
Bladder Cancer Cells

Curcumin, the primary bioactive component isolated from turmeric, has been shown to possess variety of biologic functions including anti-cancer activity. However, meticulous mechanism of the curcumin in gall bladder cancer has not been explored yet. Therefore, in our study, we elucidated the mechanism of the anticancer action of curcumin against human gall bladder cancer cells. It was found that the curcumin treated GBC cells decreased cell viability in a dose and time-dependent manner. Nuclear condensation, Annexin V-FITC/PI positive cells, and caspase-3 activation confirmed the apoptotic induction due to anti-proliferative action of curcumin. Furthermore, curcumin induced disruption in the mitochondrial membrane potential and increased reactive oxygen species generation which has not yet been reported in earlier studies of curcumin with gall bladder cancer. Moreover, curcumin-induced apoptosis of gall bladder cancer cells was also accompanied by significant amount of growth arrest at the G0/G1 phase of the cell cycle which has also not been documented previously. To the best part of my knowledge, this study has established curcumin as one of the promising chemotherapeutic agent against gall bladder carcinoma. Thus the present study explored a novel mechanism explaining the anti cancerous effects of curcumin, and may provide an alternative therapeutic approach which can overcome the side effects of chemotherapy. Keywords: Gall bladder carcinoma Curcumin; Cell cycle analysis; Caspase-3; Apoptosis

scholarly journals Calotropis procera Selectively Impaired the 4T1 Breast Cancer Cells Growth by Preferentially Blocking Akt/mTOR Signaling

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 278-278
Author(s):  
Ana Carolina Silveira Rabelo ◽  
Maria Angelica Miglino ◽  
Shirley Arbizu ◽  
Susanne Talcott ◽  
Ana Cláudia Carreira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Viability ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Calotropis Procera ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
4T1 Breast Cancer

Abstract Objectives To investigate the mechanisms underlying the anticancer activity of Calotropis procera crude phenolics extract (CphE). Methods CphE were obtained from leaves homogenized with ethanol (1g:150 mL), followed by filtration and evaporation using a rotary evaporator. Quercetin was used as a positive control since is one of the major flavonoids in C. procera. 4T1 cells were treated with CphE (31–500 µg gallic acid equivalent (GAE)/mL), quercetin (Q) (0.6–3 µg/mL) or DMSO (control) to assess cell viability using resazurin kit and reactive oxygen species (ROS) using the Carboxy-H2DFFDA probe (Sigma-Aldrich, St Louis, MO). Protein and mRNA expression were investigated using standard procedures and cell migration by wound healing assay. Results 4T1 cell viability was inhibited by CphE (within 31–125 µg GAE/mL) and Q (0.6–3 µg/mL) in a dose-dependent manner, with IC50 = 49.6 µg GAE/mL and 1,75 µg/mL, respectively. However, ROS levels were decreased in cells treated with CphE (down to 0.7-fold of control) while Q induced ROS (up to 1.5-fold of control). These results suggest a contrasting response from 4T1 breast cancer cells to individual phenolics present in CphE. The CphE-induced caspase and PARP-dependent apoptosis and cell viability suppression were mediated by CphE-mediated oxidative stress reduction consistent with phospho-ERK1/2 downregulation (down to 0.4-fold of control). Conversely, Q apoptotic and cell viability suppression mechanisms are mediated by induction of ROS-phospho-ERK1/2 (up to 1.6-fold of control) axis. The Akt/mTOR/CREB pathway was downregulated at a similar extend by CphE and Q, consistent with cell migration (suppressed by 40% and 20% by CphE and Q, respectively) and with protein levels of phospho-Src (downregulated to ∼ 0.2-fold and 0.4-fold of control) and phospho-CREB (0.7-fold and 0.6-fold of control) by CphE and Q, respectively. Conclusions CphE inhibited cell viability, induced apoptosis and reduced cell migration. These effects were the result of the modulation of proteins that play an important role in epithelial-mesenchymal transition and cell invasion. These findings provide new insights into the anti-cancer mechanisms of C. procera as a promising herb used in folk medicine for breast cancer treatment. Funding Sources Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Universidade de São Paulo (USP).

scholarly journals Evaluation of the antiproliferative effect of Iso-mukaadial acetate on breast and ovarian cancer cells

2021 ◽  
Author(s):  
Portia P Raphela-Choma ◽  
Mthokozisi BC Simelane ◽  
Mpho S Choene
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Breast And Ovarian Cancer ◽  
Cycle Arrest

Abstract Background Natural compounds derived from various medicinal plants may activate several physiological pathways which can be valuable to diseases such as cancer. Isomukaadial acetate has previously been shown to possess antimalarial and anti-diabetic properties. The purpose of this study was to evaluate the antiproliferative effects of isomukaadial acetate on breast and ovarian cancer cell lines. Method Cell viability assays were conducted using AlamarBlue assay and xCELLigence system. Cell apoptosis and cell cycle arrest were determined and analyzed by flow cytometer. Effector caspase (3/7) activation was evaluated by caspase Glo®-3/7 reagent and gene expression was analyzed by Real-Time Polymerase Chain Reaction. Results The Alamar blue assay and xCELLigence showed that Iso-mukaadial acetate exhibited anti-proliferative effects on MDA-MB 231, RMG-1, and HEK 293 cell lines in a concentration-dependent manner. Iso-mukaadial acetate induced apoptosis in both cancer cell lines caused cell cycle arrest at the S phase (RMG-1) and early G2 phase (MDA-MB 231) and expressed caspase 3/7 activity in MDA-MB 231 and RMG-1 cells. BAX and p21 were upregulated in MDA-MB 231 and RMG-1 cells after treatment. Conclusion IMA significantly inhibited cancer growth and induced cell apoptosis with cell cycle modulation. IMA may be considered a promising candidate for the development of anticancer drugs either for its cytotoxic or cytostatic effect Furthermore, IMA requires to be further studied more to clearly understand its mechanism of action on cancer cells.

Effect of arsenic trioxide on epithelial-mesenchymal transition via induction of SH2?containing protein tyrosine phosphatase 1.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 76-76
Author(s):  
Jong-Jae Park ◽  
Moon Kyung Joo ◽  
Hyo Soon Yoo ◽  
Beom Jae Lee ◽  
Taehyun Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Protein Tyrosine Phosphatase ◽  
Epithelial Mesenchymal Transition ◽  
Tyrosine Phosphatase ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Protein Tyrosine ◽  
Dose Dependent

76 Background: Arsenic trioxide (ATO) is known to inhibit epithelial-mesenchymal transition (EMT) in hepatolocellular carcinoma and breast cancer cells, however, little has been reported in gastric cancer cells. In this study, we aimed to investigate the mechanism of ATO to inhibit signal transducer and activator of transcription 3 (STAT3) activity and EMT in gastric cancer cells. Methods: We performed wound closure assay and Matrigel invasion assay for functional studies of EMT, and western blot for measurement of protein markers using AGS gastric cancer cells. Results: Compared with control, 5 and 10 μM of ATO significantly inhibited cellular migration and inhibition in a dose-dependent manner. Furthermore, ATO significantly downregulated snail expression, a mesenchymal marker, and upregulated E-cadherin expression, an epithelial marker. We could observe that ATO induced SH2-containing protein tyrosine phosphatase 1 (SHP1), a non-receptor type protein tyrosine phosphatase, and subsequently downregulated phospho-STAT3 in a dose-dependent manner. To validate the molecular link between ATO and SHP1 to inhibit EMT in gastric cancer cell, we pre-treated 50 μM of pervanadate, a phosphatase inhibitor, before treatment of 10 μM ATO, and this significantly abolished anti-invasive effect by ATO in AGS cells. In xenograft tumor model, intraperitoneal injection of ATO significantly reduced the tumor volume and upregulated SHP-1 expression by immunohistochemistry stain compared with vehicle, which were reversed by ATO with pervanadate injection. Conclusions: Our findings suggest that ATO may show anti-EMT effects via induction of SHP1 and inhibition of STAT3 activity in gastric cancer cells.

Involvement of NF-κB activation in the apoptosis induced by extracellular adenosine in human hepatocellular carcinoma HepG2 cellsThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 705-714 ◽  
Author(s):  
Ling-Fei Wu ◽  
Guo-Ping Li ◽  
Jian-Dong Su ◽  
Ze-Jin Pu ◽  
Jia-Lin Feng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Flow Cytometry ◽  
Mtt Assay ◽  
Cell Apoptosis ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Human Hepatocellular Carcinoma ◽  
Pyrrolidine Dithiocarbamate ◽  
Dependent Manner

Adenosine can exhibit cytotoxic activity in vivo and in vitro, though its mechanisms are still uncertain. In this study, we investigated the adenosine-mediated apoptotic signaling pathway and the role of NF-κB in human hepatocellular carcinoma HepG2 cells. HepG2 cells were treated with different concentrations of adenosine for 12–48 h, and the effect of adenosine on cell proliferation was evaluated by MTT assay. The cytotoxicity of adenosine alone or in combination with an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), was also evaluated by MTT assay and the mode of cell death was detected by Hoechst 33342 staining. Cell cycle progress was performed by flow cytometry with PI staining. The protein expressions of Bcl-2, p53, NF-κB subunit p65, and caspase-3 were assayed by Western blot. Caspase-3 activity was measured by spectrophotomteric assay. The results showed that adenosine significantly reduced the viability of HepG2 cells in a dose- and time-dependent manner, with IC 50 (24 and 48 h) of 2.52 and 1.89 mmol·L–1, respectively. The apoptotic index (percentage of sub-G1 phase) of HepG2 cells in adenosine treatment alone for 12 and 24 h or in combination with PDTC were 8.30%, 22.32% and 20.18%, 30.89%, respectively. All of them were higher than that in the control group (0.81%, p < 0.01). The characteristic changes of cell apoptosis (chromatin condensation and sub-G1 peak) were observed under fluorescent microscopy and flow cytometry. We also found that the apoptotic process triggered by adenosine was involved in G0–G1 cell-cycle arrest, enhanced the activity of caspase-3, upregulated p53 and NF-κB p65 expression, and downregulated Bcl-2 expression. Inhibition of NF-κB by PDTC decreased NF-κB p65 expression, enhanced cell apoptosis ratio, and increased caspase-3 activity. NF-κB may play an anti-apoptosis role in adenosine-induced HepG2 cytotoxicity.

scholarly journals Anethole induces anti-oral cancer activity by triggering apoptosis, autophagy and oxidative stress and by modulation of multiple signaling pathways

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Camille Contant ◽  
Mahmoud Rouabhia ◽  
Lionel Loubaki ◽  
Fatiha Chandad ◽  
Abdelhabib Semlali
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Kinase Inhibitor ◽  
Epithelial Mesenchymal Transition ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
And Oxidative Stress

AbstractOral cancer is one of the major public health problems. The aim of this study was to evaluate the effects of anethole, 1-methoxy-4-[(E)-1-propenyl]-benzene, on growth and apoptosis of oral tumor cells, and to identify the signaling pathways involved in its interaction with these cancer cells. Cancer gingival cells (Ca9-22) were treated with different concentrations of anethole. Cell proliferation and cytotoxic effects were measured by MTT and LDH assays. Cell death, autophagy and oxidative stress markers were assessed by flow cytometry while cell migration was determined by a healing capacity assay. The effect of anethole on apoptotic and pro-carcinogenic signaling pathways proteins was assessed by immunoblotting. Our results showed that anethole selectively and in a dose-dependent manner decreases the cell proliferation rate, and conversely induces toxicity and apoptosis in oral cancer cells. This killing effect was mediated mainly through NF-κB, MAPKinases, Wnt, caspase 3, 9 and PARP1 pathways. Anethole showed an ability to induce autophagy, decrease reactive oxygen species (ROS) production and increased intracellular glutathione (GSH) activity. Finally, anethole treatment inhibits the expression of oncogenes (cyclin D1) and up-regulated cyclin-dependent kinase inhibitor (p21WAF1), increases the expression of p53 gene, but inhibits the epithelial-mesenchymal transition markers. These results indicate that anethole could be a potential molecule for the therapy of oral cancer.

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