Affiliations 

  • 1 Malaysian Institute of Pharmaceuticals & Nutraceuticals, National Institutes of Biotechnology Malaysia (NIBM), Ministry of Science, Technology & Innovation, Halaman Bukit Gambir, Pulau Pinang, Malaysia; Advanced Medical & Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia
  • 2 Malaysian Institute of Pharmaceuticals & Nutraceuticals, National Institutes of Biotechnology Malaysia (NIBM), Ministry of Science, Technology & Innovation, Halaman Bukit Gambir, Pulau Pinang, Malaysia; Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Kuala Terengganu, Terengganu, Malaysia
  • 3 Malaysian Institute of Pharmaceuticals & Nutraceuticals, National Institutes of Biotechnology Malaysia (NIBM), Ministry of Science, Technology & Innovation, Halaman Bukit Gambir, Pulau Pinang, Malaysia; Advanced Medical & Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia. Electronic address: tanml@usm.my
Toxicol Appl Pharmacol, 2016 06 01;300:55-69.
PMID: 27049118 DOI: 10.1016/j.taap.2016.03.017

Abstract

14-Deoxy-11,12-didehydroandrographolide (14-DDA), a major diterpenoid isolated from Andrographis paniculata (Burm.f.) Nees, is known to be cytotoxic and elicits a non-apoptotic cell death in T-47D breast carcinoma cells. In this study, the mechanistic toxicology properties of 14-DDA in T-47D cells were further investigated. 14-DDA is found to induce the formation of endoplasmic reticulum (ER) vacuoles and autophagosomes, with concurrent upregulation of LC3-II in the breast carcinoma cells. It stimulated an increase in cytosolic calcium concentration and caused a collapse in mitochondrial membrane potential in these cells. In addition, both DDIT3 and GADD45A, molecules implicated in ER stress pathway, were significantly upregulated. DDIT3 knockdown suppressed the formation of both ER vacuoles and autophagosomes, indicating that 14-DDA-induced ER stress and autophagy is dependent on this transcription factor. Collectively, it is possible that GADD45A/p38 MAPK/DDIT3 pathway is involved in the 14-DDA-induced ER-stress-mediated autophagy in T-47D cells.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.