Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human...

Area of Science:

• Oncology
• Pharmacology
• Mycology

Background:

• Chondrosarcoma is a primary bone tumor with poor response to conventional treatments.
• Endophytic fungi are a source of novel bioactive compounds.
• Nalanthamala psidii is an endophytic fungus with potential medicinal properties.

Purpose of the Study:

• To investigate the anti-tumor activity of trichodermin, a metabolite from Nalanthamala psidii, against human chondrosarcoma cells.
• To elucidate the mechanisms of trichodermin-induced cell death in chondrosarcoma.

Main Methods:

• In vitro studies using human chondrosarcoma cell lines (JJ012, SW1353) and primary chondrocytes.
• Analysis of endoplasmic reticulum (ER) stress markers (IRE1, p-PERK, GRP78, GRP94) and cytosolic calcium levels.
• Assessment of mitochondrial dysfunction markers (Bax, Bid, Bcl-2, cytochrome c release, caspase-3 activation).
• In vivo studies using animal models to evaluate tumor volume and cell death markers (TUNEL, cleaved PARP).

Main Results:

• Trichodermin selectively induced apoptosis in chondrosarcoma cells but not primary chondrocytes.
• Trichodermin triggered ER stress and altered cytosolic calcium levels.
• Mitochondrial dysfunction, including cytochrome c release and caspase-3 activation, was observed.
• In vivo experiments showed reduced tumor volume and increased markers of apoptosis.

Conclusions:

• Trichodermin exhibits significant anti-tumor activity against human chondrosarcoma both in vitro and in vivo.
• The anti-cancer effects are mediated through the induction of mitochondrial dysfunction and ER stress.
• Trichodermin represents a promising novel therapeutic agent for chondrosarcoma treatment.