# In Vitro Anti-Glioblastoma Activity of a Novel Pt(IV)-Ganoderic Acid A Conjugate

## TL;DR

A new platinum-based compound shows strong anti-glioblastoma effects in lab tests, potentially offering a better treatment option for this aggressive brain cancer.

## Contribution

A novel Pt(IV)-Ganoderic Acid A conjugate is developed and shown to effectively target glioblastoma cells with minimal harm to normal cells.

## Key findings

- Pt(IV)Ac-GA significantly reduced the viability of U251 and T98G glioblastoma cells.
- The compound induced apoptosis and cell cycle arrest in cancer cells.
- Pt(IV)Ac-GA increased sensitivity to ferroptosis and mitochondrial dysfunction.

## Abstract

Glioblastoma is the most aggressive primary malignant tumor of the central nervous system in adults, with a poor prognosis and high resistance to conventional therapies. Platinum drugs like cisplatin are effective but limited by systemic toxicity, poor blood–brain barrier penetration, and resistance. Natural compounds are increasingly studied for their anticancer potential and ability to enhance existing therapies. Based on this rationale, we designed Pt(IV)Ac-GA, a novel platinum(IV) complex obtained by conjugating cisplatin with ganoderic acid A, a triterpenoid from Ganoderma lucidum known for anticancer and immunomodulatory effects. The compound was synthesized, structurally characterized, and showed high stability and favorable pharmacokinetics. In vitro, Pt(IV)Ac-GA strongly reduced the viability of U251 and T98G glioblastoma cells while sparing normal astrocytes. It triggered apoptosis, cell cycle arrest, impaired migration, and increased sensitivity to ferroptosis and mitochondrial dysfunction. These results highlight Pt(IV)Ac-GA as a promising candidate to overcome current limitations in glioblastoma treatment.