scholarly journals Ethyl acetate extract of Elephantopus mollis Kunth induces apoptosis in human gastric cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tran Dang Thanh Tam ◽  
Truong Thi Bich Ngoc ◽  
Nguyen Thi Hoai Nga ◽  
Nguyen Thi My Trinh ◽  
Tran Linh Thuoc ◽  
...  

Abstract Background Gastric cancer is one of the most leading causes of cancer death worldwide. Therefore, treatment studies have been being conducted, one of which is screening of novel agents from medicinal herbs. Elephantopus mollis Kunth (EM) belonging to Asteraceae family is a perennial herb with several therapeutic properties including anticancer activity. However, the effect of this species on gastric cancer has not been reported yet. In this study, cytotoxicity of different EM crude extracts was investigated on AGS gastric cancer cell line. Besides, the effects of extract on nuclear morphology, caspase-3 activation, and gene expression were also explored. Results The results showed that ethyl acetate extract exhibited a remarkably inhibitory ability (IC50 = 27.5 μg/ml) on the growth of AGS cells, while causing less toxicity to normal human fibroblasts. The extract also induced apoptotic deaths in AGS cells as evidenced by cell shrinkage, formation of apoptotic bodies, nuclear fragmentation, caspase-3 activation, and the upregulation of BAK and APAF-1 pro-apoptotic genes related to mitochondrial signaling pathway. Specifically, BAK and APAF-1 mRNA expression levels showed 2.57 and 2.71-fold increases respectively. Conclusions The current study not only proved the anti-gastric cancer activity of EM ethyl acetate extract but also proposed its molecular mechanism. The extract could be a potential candidate for further investigation.

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1206-1214
Author(s):  
Rui Su ◽  
Enhong Zhao ◽  
Jun Zhang

Abstract MicroRNAs (miRNAs) operate as tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis, and metabolic process. In the present research, we investigated the effect and mechanism of miR-496 in human gastric cancer cells. miR-496 was downregulated in two gastric cancer cell lines, AGS and MKN45, compared with normal gastric epithelial cell line GES-1. miR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. miR-496 mimics induced the apoptosis through upregulating the levels of Bax and Active Caspase 3 and downregulating the levels of Bcl-2 and Total Caspase 3. Bioinformatics analysis showed that there was a binding site between miR-496 and Lyn kinase (LYN). miR-496 mimics could inhibit the expression of LYN in AGS cells. LYN overexpression blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment for gastric cancer.


2020 ◽  
Vol 39 (8) ◽  
pp. 1031-1045
Author(s):  
F Shabani ◽  
M Mahdavi ◽  
M Imani ◽  
MA Hosseinpour-Feizi ◽  
N Gheibi

Calprotectin is a heterodimeric EF-hand Ca2+ binding protein that is typically released by infiltrating polymorphonuclear leukocytes and macrophages. This protein is a key player linking inflammation and cancer. Due to the increased levels of calprotectin in different inflammatory diseases and cancer, it is considered as a marker for diagnostic purposes. In this study, we evaluated the mechanism of cell viability and apoptotic-inducing effects of recombinant human calprotectin (rhS100A8/S100A9) on the gastric adenocarcinoma (AGS), the most common type of gastric cancer cell line. AGS cells were exposed to the different concentrations (5–100 μg/ml) of calprotectin for 24, 48, and 72 h, and cell viability was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic-inducing effects of calprotectin were evaluated by sub-G1 cell cycle assay and Annexin V/propidium iodide double staining. Furthermore, real-time polymerase chain reaction and Western blot analysis were performed to evaluate the mechanism of action of calprotectin. Our findings indicated that calprotectin inhibits growth and viability of AGS cells in a time- and dose-dependent manner. The half-maximal inhibitory concentration values were measured as 85.77, 79.14, and 65.39 μg/ml for 24, 48, and 72 h, respectively. Additionally, we found that calprotectin downregulated the expression of antiapoptotic protein Bcl-2 and upregulated proapoptotic protein Bax in a time- and concentration-dependent fashion. Calprotectin also slightly upregulated the expression of extracellular signal-regulated protein kinase 2 (ERK2), while it significantly decreased the levels of phospho-ERK in a time-dependent manner. Overall, these findings indicated that calprotectin has cytotoxicity and apoptosis-inducing effects on AGS cell lines in high concentration by modulating Bax/Bcl-2 expression ratio accompanied by inhibition of ERK activation.


Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 784
Author(s):  
Wongwarut Boonyanugomol ◽  
Kamolchanok Rukseree ◽  
Pornpan Prapatpong ◽  
Onrapak Reamtong ◽  
Seung-Chul Baik ◽  
...  

The effects of Ocimum tenuiflorum essential oil (OTEO) against gastric cancer remain unknown and merit investigation. In the present study, the anti-cancer activity of OTEO was examined in a human gastric cancer cell line (AGS). After OTEO treatment, AGS cell viability was determined by an MTT assay, and inhibition of metastasis was determined by cell migration and invasion assays. The expression of apoptosis-related genes in treated AGS cells was determined by qRT-PCR. OTEO significantly decreased AGS cell viability in a dose-dependent manner (IC50 163.42 µg/mL) and effectively inhibited cell migration and invasion. Morphological examination demonstrated that OTEO induced cell shrinkage, chromatin condensation, and fragmentation, which are considered typical morphologies of apoptotic cell death. Pro-apoptotic genes (TP53, BAX, and BAK) were significantly up-regulated, while anti-apoptotic genes (BCL-2 and BCL-xL) were significantly down-regulated after treatment with OTEO. In addition, significantly increased gene expression was detected for CASP8, CASP9, and CASP3 in AGS cells exposed to OTEO. GC-MS analysis demonstrated that the major compound of OTEO was caryophyllene (25.85%) and α-pinene (11.66%). This in vitro study demonstrates for the first time that OTEO has potential anti-gastric cancer activity and may induce apoptosis in AGS cells through extrinsic and intrinsic pathways.


Author(s):  
Hui Ling ◽  
Liang-Yun Zhang ◽  
Qi Su ◽  
Ying Song ◽  
Zhao-Yang Luo ◽  
...  

AbstractDiallyl disulfide (DADS) is a major constituent of garlic. Previously, we found that DADS both inhibited proliferation in human gastric cancer cells in vitro and in vivo, and induced G2/M arrest. In this study, we investigated whether this differentiation effect was induced by DADS in human gastric cancer MGC803 cells, and whether it was related to an alteration in ERK activity. The results showed that the growth of MGC803 cells was inhibited by DADS. Cells treated with DADS displayed a lower nucleocytoplasmic ratio and tended to form gland and intercellular conjunction structures. The ConA-mediated cell agglutination ratio and cells’ ALP specific activity decreased. In MGC803 cells, dye transfer was limited to a few cells neighbouring the dye-injected cell and to a depth of 1–2 layers beneath the scrape site. However, after treatment with DADS, the LY (Lucifer Yellow) was transferred to several cells immediately neighbouring the microinjected cell and to a depth of 2–4 cell layers from the scrape site. This indicated that DADS induced differentiation in MGC803 cells. Western blot analysis revealed that although DADS did not influence the quantity of ERK1/2 protein expressed, it did decrease its phosphorylation in a concentration-dependent manner, compared with the controls. At 30 mg·L−1, DADS inhibited the activation of ERK1/2 in 15–30 min. These results suggested that the DADS-induced differentiation of MGC803 cells involved an alteration of the ERK1/2 signaling pathway.


2019 ◽  
Vol 111 ◽  
pp. 76-85 ◽  
Author(s):  
Yi-Qiang Zhang ◽  
Jin-Hong Pei ◽  
Shuai-Shuai Shi ◽  
Xiao-su Guo ◽  
Guo-yan Cui ◽  
...  

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