Artocarpin induces cell apoptosis in human osteosarcoma cells through endoplasmic reticulum stress and reactive...

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Osteosarcoma is a primary bone cancer with limited treatment options.
• Chemotherapy and radiation therapy show poor efficacy and significant side effects.
• There is a critical need for novel and effective adjuvant therapies for osteosarcoma.

Purpose of the Study:

• To investigate the potential anticancer effects of artocarpin, a flavonoid derivative, against osteosarcoma.
• To elucidate the molecular mechanisms underlying artocarpin's anti-osteosarcoma activity.

Main Methods:

• In vitro studies using human osteosarcoma cell lines (U2OS, MG63, HOS).
• Assessment of artocarpin-induced apoptosis, reactive oxygen species (ROS) generation, and mitochondrial dysfunction.
• Analysis of endoplasmic reticulum (ER) stress markers and caspase pathway activation.
• In vivo studies using murine tumor models to evaluate tumor volume reduction.

Main Results:

• Artocarpin induced significant apoptosis in all tested osteosarcoma cell lines.
• Increased intracellular ROS and mitochondrial dysfunction, including cytochrome c release, were observed.
• Artocarpin triggered endoplasmic reticulum stress and modulated Bcl-2 family proteins (Bcl-2, Bcl-xL, Bak, Bax).
• In vivo studies showed a 40% reduction in tumor volume after artocarpin treatment.

Conclusions:

• Artocarpin exhibits potent anticancer activity against osteosarcoma cells through ROS generation, ER stress, mitochondrial pathway, and caspase activation.
• Artocarpin demonstrates significant tumor-inhibitory effects in vivo.
• Artocarpin represents a promising novel therapeutic agent for osteosarcoma treatment.