Gelsemium elegans cyclic peptide induces human cervical carcinoma cells apoptosis through intrinsic and extrinsic...

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Molecular Biology

Background:

• Cervical cancer remains a significant global health challenge.
• Natural products are a valuable source for novel therapeutic agents.
• Gelsemium elegans contains bioactive compounds with potential medicinal properties.

Purpose of the Study:

• To isolate and characterize novel cyclic peptides from Gelsemium elegans.
• To evaluate the antihuman cervical carcinoma activity of these peptides.
• To elucidate the mechanism of action of the most potent peptide.

Main Methods:

• Isolation and structure elucidation of four novel Gelsemium elegans cyclic peptides (GEPs).
• In vitro antiproliferative assays using HeLa cells.
• Analysis of apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial pathway activation.
• Investigation of the extrinsic death receptor pathway.

Main Results:

• Four novel GEPs were identified, with GEP-1 exhibiting significant antihuman cervical carcinoma activity.
• GEP-1 inhibited HeLa cell proliferation dose- and time-dependently.
• GEP-1 induced apoptosis via caspase-dependent pathways, ROS overproduction, and mitochondrial dysfunction (cytochrome c, AIF, Endo G release).
• GEP-1 activated the extrinsic pathway through Fas and FADD.

Conclusions:

• GEP-1, a novel cyclic peptide from Gelsemium elegans, demonstrates potent antihuman cervical carcinoma activity.
• GEP-1 induces cancer cell death through multiple apoptotic pathways.
• GEP-1 represents a promising lead compound for the development of new cervical cancer therapeutics.