Roundup-Induced AMPK/mTOR-Mediated Autophagy in Human A549 Cells

Area of Science:

• Environmental Science
• Toxicology
• Cell Biology

Background:

• Extensive pesticide use poses environmental and human health risks.
• Glyphosate-based herbicides (GBHs) are widely used, targeting a pathway absent in vertebrates.
• Understanding the specific effects of commercial GBH formulations is crucial.

Purpose of the Study:

• To investigate the autophagic effects of a commercial glyphosate-based herbicide, Roundup (RDP), on human A549 cells in vitro.
• To determine whether the observed effects are due to the active ingredient (glyphosate isopropylamine salt) or the adjuvant (polyethoxylated tallow amine).
• To explore the underlying molecular mechanisms, including AMPK/mTOR signaling.

Main Methods:

• In vitro study using human A549 lung cancer cells.
• Intracellular biochemical assays to measure markers of autophagy and mitochondrial activity.
• Analysis of key proteins involved in the AMPK/mTOR pathway.

Main Results:

• Roundup (RDP) induced mitochondrial permeability transition pore opening in A549 cells.
• RDP treatment led to increased LC3-II conversion and beclin-1, with decreased p62, indicating autophagy.
• These effects were attributed to the adjuvant polyethoxylated tallow amine, not the glyphosate active ingredient.
• RDP modulated the phosphorylation of AMPK and mTOR, suggesting AMPK/mTOR-mediated autophagy.

Conclusions:

• Roundup (RDP) induces cell autophagy in human A549 cells via AMPK/mTOR pathway activation.
• The adjuvant polyethoxylated tallow amine is responsible for the observed autophagic effects, not glyphosate.
• This research provides a basis for understanding the health risks associated with GBH adjuvants.