Methyloleanolate Induces Apoptotic And Autophagic Cell Death Via Reactive Oxygen Species Generation And c-Jun
Myoung Seok Jeong1, Ji Hoon Jung1, Hyemin Lee1
1College of Korean Medicine, Kyung Hee University, Dongdaemun-Gu, Seoul 02447, Republic of Korea.
Background:
To develop a potent anticancer agent similar to oleanolate, the underlying mechanisms of its derivative, methyloleanolate, in the apoptosis and autophagy of A549 and H1299 cells were elucidated.
Purpose:
The aim of the present study was to investigate the effect of methyloleanolate in inducing apoptotic and autophagic cell death in cancer cells.
Materials And Methods:
Flow cytometric analysis with Annexin V/PI staining, Western blot analysis, and immunofluorescence analysis were conducted in A549 and H1299 cells.
Results:
Methyloleanolate increased the fraction of Annexin V/PI apoptotic cells and activated caspase-8, caspase-3, and death receptor 5 (DR5) more than oleanolate in A549 and H1299 cells pretreated with pancaspase inhibitor z-VAD-fmk and DR5 depletion. Also, methyloleanolate induced autophagic features of microtubule-associated protein light chain 3 3BII (LC3BII) conversion and puncta in A549 and H1299 cells, along with autophagosomes and vacuoles. Methyloleanolate blocked autophagy flux for impaired autophagy and chloroquine (CQ)-enhanced microtubule-associated protein LC3BII accumulation and cytotoxicity in A549 and H1299 cells, although 3-methyladenine (3-MA) did not. Interestingly, LC3BII accumulation was detected only in methyloleanolate-treated autophagy-related gene 5 (ATG5)+/+ mouse embryonic fibroblast (MEF) cells but not in ATG5 -/- MEF cells. Methyloleanolate reduced p-mTOR but activated p-c-Jun N-terminal kinases and reactive oxygen species production in A549 and H1299 cells. Conversely, n-acetyl-l-cysteine and SP600125 blocked apoptotic and autophagic cascades caused by methyloleanolate in A549 and H1299 cells.
Conclusion:
Overall, the findings suggest that methyloleanolate induces apoptotic and autophagic cell death in non-small cell lung cancers via reactive oxygen species generation and c-Jun N-terminal kinase phosphorylation.
More Related Videos
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
06:12Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
Published on: May 3, 2024
Related Concept Videos
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
The Intrinsic Apoptotic Pathway
Apoptosis
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
The Extrinsic Apoptotic Pathway
MAPK Signaling Cascades
