Extract from <italic style="font-style: italic">Zanthoxylum piperitum</italic> Induces Apoptosis of AGS Gastric Cancer Cells through Akt/MDM2/p53 Signaling Pathway*

Ye Seul Park; Gun He Nam; Kyung Jo Jo; Hye Won Kawk; Sang Yung Kim; Young Min Kim

doi:10.1007/s11655-021-3486-8

Your Location：

Home >

Browse articles >

Extract from Zanthoxylum piperitum Induces Apoptosis of AGS Gastric Cancer Cells through Akt/MDM2/p53 Signaling Pathway*

Original Article | Updated：2021-10-18

- Extract from Zanthoxylum piperitum Induces Apoptosis of AGS Gastric Cancer Cells through Akt/MDM2/p53 Signaling Pathway*
- Chinese Journal of Integrative Medicine Vol. 27, Issue 10, Pages: 752-759(2021)
- Affiliations：
  
  1.Department of Biological science and Biotechnology, College of Life science and Nano Technology, Hannam University, 1646 Yuseong-daero, Yuseong-gu, Daejeon 34054, South Korea
  2.Department of Food Science & Bio Technology, Shinansan University, Deahakro Danwon-gu, Ansan-City, Gyenggi-do,Korea
- Author bio：
  
  Prof. Young Min Kim, E-mail: ym1938@naver.com
- Funds：
- DOI：10.1007/s11655-021-3486-8
  CLC：
- Published：01 October 2021，
  
  Published Online：28 July 2021，
  
  Accepted：23 September 2019
Scan for full text
Ye Seul Park, Gun He Nam, Kyung Jo Jo, et al. Extract from Zanthoxylum piperitum Induces Apoptosis of AGS Gastric Cancer Cells through Akt/MDM2/p53 Signaling Pathway*. [J]. Chinese Journal of Integrative Medicine 27(10):752-759(2021)
DOI：

Ye Seul Park, Gun He Nam, Kyung Jo Jo, et al. Extract from Zanthoxylum piperitum Induces Apoptosis of AGS Gastric Cancer Cells through Akt/MDM2/p53 Signaling Pathway*. [J]. Chinese Journal of Integrative Medicine 27(10):752-759(2021) DOI： 10.1007/s11655-021-3486-8.

摘要

Abstract

Objective:

To determine the effect of Zanthoxylum piperitum extracet (ZPE) on apoptosis and analyze anticancer substances in ZPE

changes in proteins related to apoptosis

and pathological changes in tumors in mouse.

Methods:

Fifteen 4-week-old female BALB/c nu/nu mice were divided into 3 groups depending on ZPE dose

with 5 in each group. AGS gastric carcinoma cells (1×10

cells/200 μL) were subcutaneously injected into the flank of each mouse. One week after the injection of AGS cells

ZPE was administered to the skin tissue [10 or 50 mg/(kg•d)] in the low- and high-dose groups

respectively for 20 days. Control animals were injected with vehicle only. After 3 weeks

the tumor was extracted and carried out for immunohistochemistry

the tendency of apoptosis and p53 in the body was checked using TdT-mediated dUTP nick-end labeling (TUNEL) assay. For 3-(4

5-dimethylthiazol-2-yl)-2

5-diphenyltetrazolium bromide (MTT) assay

annexin V dead cell staining

cell cycle arrest and Western blotting

AGS gastric carcinoma cells were incubated with various concentrations of ZPE for 24 h. Cell survival rates were analyzed by MTT assays. Apoptosis was analyzed using annexin V dead cell staining and cell cycle arrest and measured using Muse cell analyzer.

Results:

High performance liquid chromatography (HPLC) analysis showed that ZPE contained organic sulfur compounds such as alliin and S-allylcysteine. MTT assay results revealed that ZPE (10–85 μg/mL) could effectively inhibit the growth of AGS gastric cancer cells at higher concentrations (

0.05

0.01). The annexin V

dead cell staining assay and cell cycle arrest assay confirmed a dose-dependent increase in the apoptosis rate and G1 phase in ZPE (10–70 μg/mL) groups. ZPE decreased the expression of anti-apoptotic proteins (p-Akt

p-MDM2

Bcl-2)

while increased pro-apoptotic proteins (cleaved PARP

p53

pro-Caspase 3

Bax). TUNEL assays revealed an increase in cell apoptosis. Immunohistochemistry staining confirmed the involvement of p53.

Conclusion:

ZPE decreases AGS cell proliferation and induces apoptosis by inhibiting Akt and MDM2 expression.

关键词

Keywords

AGS gastric cancer cellsZanthoxylum piperitumapoptosisAkt/MDM2/p53 signaling pathwayactive compounds

references

Yamazaki E, Inagaki M, Kurita O, Inoue T. Antioxidant activity of Japanese pepper (Zanthoxylum piperitum DC.)fruit. Food Chem X 2007:100.1:171-177.

Jang MJ, Rhee SJ, Cho SH, Woo MH, Choi JH. A study on the antioxidative, anti-inflammatory and anti-thrombogenic effects of Zanthoxylum piperitum DC. extract. J Kor Soc Food Sci Nutr 2006:351:21-27.

Kweon SS. Updates on cancer epidemiology in Korea, 2018. Chonnam Med J 2018:54:90-100.

Park HA, Nam SY, Lee SK. The Korean guideline for gastric cancer screening. J Kor Med Assoc 2015;58:373-384.

Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 2011;30:87.

Yang C, Du W, Yang D. Inhibition of green tea polyphenol EGCG ((–)-epigallocatechin-3-gallate) on the proliferation of gastric cancer cells by suppressing canonical Wnt/β-catenin signalling pathway. Int J Food Sci Nutr 2016;67:818-827.

Saraswathy M, Gong S. Different strategies to overcome multidrug resistance in cancer. Biotechnol Adv 2013;31:1397-1407.

Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci 2005;78:431-441.

Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol 2017;14:417.

Khanna P, Chua PJ, Bay BH, Baeg GH. The JAK/STAT signaling cascade in gastric carcinoma. Int J Oncol 2015:47:1617-1626.

Han SI, Kim YS, Kim TH. Role of apoptotic and necrotic cell death under physiologic conditions. BMB Rep 2008:41:1-10.

Jin Z, El-Deiry WS. Overview of cell death signaling pathways. Cancer Biol Ther 2005:4:147-171.

Berghe TV, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol 2014;15:135-147.

Oh YN, Jin S, Park HJ, Kim BW, Kwon HJ. Anti-oxidative and anti-cancer activities of Treculia Africana extract in human colon adenocarcinoma HT29 cells. J Life Sci 2015;25:515-522.

Rizzuto R, Giorgi C, Romagnoli A, Pinton P. Ca2+ signaling,mitochondria and cell death. Curr Mol Med 2008;8:119-130.

Suen DF, Norris KL, Youle RJ. Mitochondrial dynamics and apoptosis. Genes Dev 2008;22:1577-1590.

Jeong YJ, Kang KJ. Effect of Angelica keiskei extract on apoptosis of MDA-MB-231 human breast cancer cells. J Kor Soc Food Sci Nutr 2011;40:1654-1661.

Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 2014;15:49.

Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci 2009;122:437-441.

Powolny AA, Singh SV. Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds. Cancer Lett 2008;269:305-314.

Oommen S, Anto RJ, Srinivas G, Karunagaran D. Allicin(from garlic) induces caspase mediated apoptosis in cancer cells. Eur J Pharmacol 2004;485:97-103.

Wang J, He HJ, He CW, Wu P, Lin JJ. Effect of allicin in antagonizing mice's bladder cancer in vitro and in vivo.Chin J Integr Med 2004;10:208-212.

Borlinghaus J, Albrecht F, Gruhlke MC, Nwachukwu ID,Slusarenko AJ. Allicin: chemistry and biological properties.Molecules 2014;19:12591-12618.

Rose P, Whiteman M, Moore PK, Zhu YZ. Bioactive S-alk(en) yl cysteine sulfoxide metabolites in the genus Allium:the chemistry of potential therapeutic agents. Nat Prod Rep 2005;22:351-368.

McCubrey JA, Steelman LS, Abrams SL, Lee JT, Chang F,Bertrand FE, et al. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv Enzyme Regul 2006;46:249-279.

Ji H, Ding Z, Hawke D, Xing D, Jiang BH, Mills GB, Lu Z. AKT-dependent phosphorylation of Niban regulates nucleophosmin- and MDM2-mediated p53 stability and cell apoptosis. EMBO Rep 2012;13:554-560.

Murray SA, Yang S, Demicco E, Ying H, Sherr DH, Hafer LJ, et al. Increased expression of MDM2, cyclin D1, and p27Kip1 in carcinogen-induced rat mammary tumors. J Cell Biochem 2005;95:875-884.

Nam GH, Jo KJ, Park YS, Kawk HW, Kim SY, Kim YM. In vitro and in vivo induction of p53-dependent apoptosis by extract of Euryale ferox Salisb in A549 human caucasian lung carcinoma cancer cells is mediated through Akt signaling pathway. Front Oncol 2019;9:406.

Marine JC, Lozano G. MDM2-mediated ubiquitylation: p53 and beyond. Cell Death Differ 2010;17:93-102.

Wang W, Hu Y. Small molecule agents targeting the p53-MDM2 pathway for cancer therapy. Med Res Rev 2012;32:1159-1196.

Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B, Bao JK. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif 2012;45:487-498.

Wang X, Simpson ER, Brown KA. p53: protection against tumor growth beyond effects on cell cycle and apoptosis. J Cancer Res 2015;75:5001-5007.

Li T, Kon N, Jiang L, Tan M, Ludwig T, Zhao Y. Tumor suppression in the absence of p53-mediated cell-cycle arrest,apoptosis, and senescence. Cell 2012;149:1269-1283.

Lin JM, Wei LH, Chen YQ, Liu XX, Hong ZF, Sferra TJ, et al.Pien Tze Huang (片仔癀)-induced apoptosis in human colon cancer HT-29 cells is associated with regulation of the Bcl-2 family and activation of caspase 3. Chin J Integr Med 2011;17:685-690.

Choi HS, Seo HS, Kim JH, Um JY, Shin YC, Ko SG.Ethanol extract of paeonia suffruticosa Andrews (PSE)induced AGS human gastric cancer cell apoptosis via fas-dependent apoptosis and MDM2-p53 pathways. J Biomed Sci 2012;19:1-12.

More>

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway

Naringin Inhibits Colorectal Carcinogenesis by Inhibiting Viability of Colorectal Cancer Cells

Therapeutic Properties of Flavonoids in Treatment of Cancer through Autophagic Modulation:A Systematic Review

Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis

Related Author

No data

Related Institution

Department of Critical Care Medicine, Jiangsu Province Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine

Department of Critical Care Medicine, Changzhou Hospital of Traditional of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine

Experimental Center for Teaching, Hebei Medical University

Department of Gynaecology and Obstetrics, Hebei Province Hospital of Chinese Medicine

Medical Examination Center, Hebei Province Hospital of Chinese Medicine

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

Extract from Zanthoxylum piperitum Induces Apoptosis of AGS Gastric Cancer Cells through Akt/MDM2/p53 Signaling Pathway*

DOI：10.1007/s11655-021-3486-8

摘要

Abstract

关键词

Keywords

references