Next Article in Journal / Special Issue
Pleiotropic Pharmacological Actions of Capsazepine, a Synthetic Analogue of Capsaicin, against Various Cancers and Inflammatory Diseases
Previous Article in Journal
Differential Proteomics Reveals miR-155 as a Novel Indicator of Liver and Spleen Pathology in the Symptomatic Niemann-Pick Disease, Type C1 Mouse Model
Previous Article in Special Issue
Bee Venom and Its Peptide Component Melittin Suppress Growth and Migration of Melanoma Cells via Inhibition of PI3K/AKT/mTOR and MAPK Pathways
Article Menu
Issue 5 (March-1) cover image

Export Article

Open AccessArticle
Molecules 2019, 24(5), 993; https://doi.org/10.3390/molecules24050993

Antrodin C, an NADPH Dependent Metabolism, Encourages Crosstalk between Autophagy and Apoptosis in Lung Carcinoma Cells by Use of an AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway

1
National Engineering Research Center of Edible Fungi, Key Laboratory of Applied Mycological Resources and Utilization of Ministry of Agriculture, Shanghai Key Laboratory of Agricultural Genetics and Breeding; Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China
2
WuXi App Tec Co, Ltd., Shanghai 200131, China
3
College of Life Sciences, Shihezi University, Shihezi 832003, China
4
Food Science College, Tibet Agriculture & Animal Husbandry University, Linzhi 860000, China
*
Authors to whom correspondence should be addressed.
Received: 3 February 2019 / Revised: 4 March 2019 / Accepted: 6 March 2019 / Published: 12 March 2019
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
Full-Text   |   PDF [4634 KB, uploaded 12 March 2019]   |  
  |   Review Reports

Abstract

The current study aims to explore the possible anti-lung carcinoma activity of ADC as well as the underlying mechanisms by which ADC exerts its actions in NSCLC. Findings showed that ADC potently inhibited the viability of SPCA-1, induced apoptosis triggered by ROS, and arrested the cell cycle at the G2/M phase via a P53 signaling pathway. Interestingly, phenomena such as autophagosomes accumulation, conversion of the LC3-I to LC3-II, etc., indicated that autophagy could be activated by ADC. The blockage of autophagy-augmented ADC induced inhibition of cell proliferation, while autophagy activation restored cell death, indicating that autophagy had a protective effect against cell death which was induced by ADC treatment. Meanwhile, ADC treatment suppressed both the Akt/mTOR and AMPK signaling pathways. The joint action of both ADC and the autophagy inhibitor significantly increased the death of SPCA-1. An in vitro phase I metabolic stability assay showed that ADC was highly metabolized in SD rat liver microsomes and moderately metabolized in human liver microsomes, which will assist in predicting the outcomes of clinical pharmacokinetics and toxicity studies. These findings imply that blocking the Akt/mTOR signaling pathway, which was independent of AMPK inhibition, could activate ADC-induced protective autophagy in non-small-cell lung cancer cells. View Full-Text
Keywords: antrodin C; apoptosis; autophagy; AKT; mTOR; metabolic stability antrodin C; apoptosis; autophagy; AKT; mTOR; metabolic stability
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Yang, H.; Bai, X.; Zhang, H.; Zhang, J.; Wu, Y.; Tang, C.; Liu, Y.; Yang, Y.; Liu, Z.; Jia, W.; Wang, W. Antrodin C, an NADPH Dependent Metabolism, Encourages Crosstalk between Autophagy and Apoptosis in Lung Carcinoma Cells by Use of an AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway. Molecules 2019, 24, 993.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top