Derrone induces autophagic cell death through induction of ROS and ERK in A549 cells

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Cudrania tricuspidata is a plant source of bioactive compounds.
• Derrone (DR) is a major compound found in unripe fruits of Cudrania tricuspidata.
• Cancer cell death mechanisms are crucial for therapeutic development.

Purpose of the Study:

• To investigate the effect of derrone (DR) on cancer cell death.
• To elucidate the mechanisms underlying DR-induced cell death, focusing on apoptosis and autophagy.
• To identify key signaling pathways involved in DR's anti-cancer activity.

Main Methods:

• Cell viability assays were performed on various cancer cell lines.
• Apoptosis was assessed through standard assays.
• Autophagic features were analyzed, including LC3 conversion and autophagosome formation.
• Reactive oxygen species (ROS) and intracellular calcium levels were measured.
• ERK phosphorylation was evaluated using Western blotting.
• Autophagy inhibitors and ROS scavengers were used to validate mechanisms.

Main Results:

• Derrone (DR) inhibited growth in multiple cancer cell lines, partially via apoptosis in A549 cells.
• DR treatment induced hallmarks of autophagy, including LC3-II conversion and p62 downregulation.
• DR-induced cell death was reversed by autophagy inhibition, indicating autophagic cell death.
• DR increased cytoplasmic Ca2+ and ROS; ROS scavengers partially rescued cell viability.
• DR treatment led to sustained ERK phosphorylation, and its inhibition attenuated DR-induced cell death.

Conclusions:

• Derrone (DR) induces autophagic cell death in A549 cancer cells.
• Intracellular ROS generation and sustained ERK phosphorylation are critical mediators of DR's effects.
• DR represents a potential therapeutic agent for cancer treatment, warranting further investigation.