Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Apoptosis-induced effects of extract from Artemisia annua Linné by modulating PTEN/p53/PDK1/Akt/ signal pathways through PTEN/p53-independent manner in HCT116 colon cancer cells

Authors: Eun Ji Kim, Guen Tae Kim, Bo Min Kim, Eun Gyeong Lim, Sang-Yong Kim, Young Min Kim

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

The extracts from Artemisia annua Linné (AAE) has been known to possess various functions including anti-bacterial, anti-virus and anti-oxidant effects. However, the mechanism of those effects of AAE is not well known. Pursuantly, we determined the apoptotic effects of extract of AAE in HCT116 cell. In this study, we suggested that AAE may exert cancer cell apoptosis through PTEN/PDK1/Akt/p53signal pathway and mitochondria-mediated apoptotic proteins.

Methods

We measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) assay, Hoechst 33342 staining, Annexin V-PI staining, Mitopotential assay, immunofluorescence (IF) and Western blotting. Accordingly, our study showed that AAE treatment to HCT116 cells resulted in inhibition of PDK1, Akt, MDM2, Bcl-2, and pro-caspase 3 as well as activation of PTEN, p53-upregulated modulator of apoptosis (PUMA), Bax and Bak expression. Also we measured in vivo assay that xenograft model, H&E assay, TUNEL assay and IHC.

Results

AAE induced apoptosis via PTEN/p53/PDK1/Akt signal pathways through PTEN/p53-independent manner. AAE inhibit cell viability and increase LDH release in HCT116 colon cancer cell. Also, AAE increase apoptotic bodies, caspase −3,7 activation and reduces mitochondria membrane potential. AAE regulates cytochrome c translocation to the cytoplasm and Bax translocation to the mitochondrial membrane in an Immunofluorescence staining and increase PTEN and p53 expression in an in vivo tumor xenograft model. To elucidate the role of the PTEN/p53/PDK1/Akt signal pathways in cancer control, we conditionally inactivated PTEN/p53/PDK1/Akt signal pathways. We used inhibitors of PTEN, p53, PDK1, Akt. In consequence, these results indicate that AAE induced apoptosis by means of a mitochondrial event through the regulation of proteins such as Bax, Bak and cytochrome c in PDK1/Akt signaling pathways via PTEM/p53-independent manner.

Conclusions

We confirmed the apoptotic effect of extracts of AAE by Modulating PTEN/p53/PDK1/Akt/Signal Pathways through PTEN/p53-independent pathwaysin HCT116 colon cancer cell.
Literature
1.
Romero MR, Serrano MA, Vallejo M, Efferth T, Alvarez M, Marin JJ. Antiviral effect of artemisinin from Artemisia annua against a model member of the Flaviviridae family, the bovine viral diarrhoea virus (BVDV). Planta Med. 2006;72:1169–74.CrossRefPubMed
2.
Manulu CE, Adelakun EA, Abok JI. Metabolites Detected in the Crude N-Hexane Extract of Artemisia annua Linn (Asteraceae) Cultivated in Langtang, Plateau State, Nigeria. Chem Sci Int J. 2017;18(2):1–6.
3.
Räth K, Taxis K, Walz G, Gleiter CH, Li SM, Heide L. Pharmacokinetic study of artemisinin after oral intake of a traditional preparation of Artemisia annua L. (annual wormwood). AmJTrop Med Hyg. 2004;70:128–32.
4.
Towler MJ, Weathers PJ. Variations in key artemisinic and other metabolites throughout plant development in Artemisia annua L. for potential therapeutic use. Ind Crop Prod. 2015;67:185–91.CrossRef
5.
Weathers PJ, Arsenault PR, Covello PS, McMickle A, Teoh KH, Reed DW. Artemisinin production in Artemisia annua: studies in planta and results of a novel delivery method for treating malaria and other neglected diseases. Phytochem Rev. 2011;10:173–83.CrossRefPubMedPubMedCentral
6.
Brisibe EA, Umoren UE, Brisibe F, Magalhaes PM, Ferreira JFS, Luthria D, Wu X, Prior RL. Nutritional characterization and antioxidant capacity of different tissues of Artemisia annua. L Food Chem. 2009;115:1240–6.CrossRef
7.
Ryu JH, Lee SJ, Kim MJ, Shin JH, Kang SK, Cho KM, Sung NJ. Antioxidant and anticancer activities of Artemisia annua L. and determination of functional compounds. J Korean Soc Food Sci Nutr. 2011;40:509–16.CrossRef
8.
Ryu JH, Kim RJ, Lee SJ, Kim IS, Lee HJ, Sung NJ. Nutritional properties and biological activities of Artemisia annua L. J Korean Soc Food Sci Nutr. 2011;40:163–70.CrossRef
9.
10.
Avery MA, Chong WKM, Jennings-White C. Stereoselective total synthesis of (+)-artemisinin, the antimalarial constituent of Artemisia annua L. J Am Chem Soc. 1992;114:974–9.CrossRef
11.
Schmid G, Hofheinz W. Total synthesis of qinghaosu. J Am Chem Soc. 1983;105:624–5.CrossRef
12.
Singh NP, Lai H. Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sci. 2001;70:49–56.CrossRefPubMed
13.
Kang JR, Lee SJ, Hwang CR, Shin J, Kang MJ, Sung NJ. Optimization of extraction conditions for mixing beverage development of black garlic and gaeddongssuk by response surface methodology. J Agric Life Sci. 2012;46:139–49.
14.
Grego-Bessa J, Bloomekatz J, Castel P, Omelchenko T, Baselga J, Anderson KV. The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium. elife. 2015; doi:10.​7554/​eLife.​12034.
15.
16.
PTEN 3, Yin Y, Shen WH. PTEN: a new guardian of the genome. Oncogene. 2008;27:5443–53.
17.
PDK1 4, Itoh Y, Higuchi M, Koji O, Kishi Y, Okazaki T, Sakai H, Miyata T, Nakajima K, Gotoh Y. PDK1–Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex. PNAS. 2016; doi:10.​1073/​pnas.​1516321113.
18.
Blanco-Aparicio C, Renner O, Leal JF, Carnero A. PTEN, more than the AKT pathway. Carcinogenesis. 2007;7:1379–86.CrossRef
19.
Vara JÁ, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M. PI3K/Akt signalling pathway and caner. Cancer Treat Rev. 2004;30:193–204.CrossRef
20.
Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell. 2003;4:257–62.CrossRefPubMed
21.
Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005;1:59–71.CrossRef
22.
Altomare DA, Testa JR. Perturbations of the AKT signaling pathway in human cancer. Oncogene. 2005;24:7455–64.CrossRefPubMed
23.
Ogawara Y, Kishishita S, Obata T, Isazawa Y, Suzuki T, Tanaka K, Masuyama N, Gotoh Y. Akt enhances Mdm2-mediated Ubiquitination and degradation of p53. J Biol Chem. 2002;24:21843–50.CrossRef
24.
25.
Bellamy COC. p53 and apoptosis. Bnhih Medical Bulletin. 1996;3:522–38.
26.
Vaseva AV, Moll UM. The mitochondrial p53 pathway. J Cai et al/Biochimica et Biophysica Acta. 2009;1787:414–20.CrossRef
27.
Cai TY, Yang J, Jones DP. Mitochondrial control of apoptosis: the role of cytochrome c. J Cai et al/Biochimica et Biophysica Acta. 1998;1366:139–49.CrossRef
28.
29.
30.
31.
BT KILE. The role of the intrinsic apoptosis pathway in platelet life and death. J Thromb Haemost. 2009;7:214–7.CrossRef
32.
33.
Fulda S, Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006;25:4798–811.CrossRefPubMed
34.
Srivastava P, Yadav N, Lella R, Schneider A, Jones A, Marlowe T, Lovett G, Loughlin KO, Minderman H, Gogada R, Chandra D. Neem oil limonoids induces p53-independent apoptosis and autophagy. Carcinogenesis. 2012;11:2199–207.CrossRef
Metadata
Title
Apoptosis-induced effects of extract from Artemisia annua Linné by modulating PTEN/p53/PDK1/Akt/ signal pathways through PTEN/p53-independent manner in HCT116 colon cancer cells
Authors
Eun Ji Kim
Guen Tae Kim
Bo Min Kim
Eun Gyeong Lim
Sang-Yong Kim
Young Min Kim
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1702-7

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue

Research article

Antibacterial activity of the stem bark of Tieghemella Heckelii Pierre ex. A Chev against methicillin-resistant Staphylococcus aureus

Research article

Survey of integrative lumbar spinal stenosis treatment in Korean medicine doctors: preliminary data for clinical practice guidelines

Research article

Hemodynamic changes caused by acupuncture in healthy volunteers: a prospective, single-arm exploratory clinical study

Research article

Acupuncture and moxibustion for chronic fatigue syndrome in traditional Chinese medicine: a systematic review and meta-analysis

Research article

Fungal 7-epi-10-deacetyltaxol produced by an endophytic Pestalotiopsis microspora induces apoptosis in human hepatocellular carcinoma cell line (HepG2)

Research article

Anti-plasmodial activity of Norcaesalpin D and extracts of four medicinal plants used traditionally for treatment of malaria