# In vitro cytotoxic mechanisms of Pt(O,O′-acac)(γ-acac)(DMS): mitochondrial dysfunction and impaired autophagy in U251 cell line

## TL;DR

This study explores a new platinum-based compound that shows better effectiveness and fewer side effects than cisplatin in treating glioblastoma.

## Contribution

The study introduces a novel platinum(II) complex with improved lipophilicity and reduced neurotoxicity for glioblastoma treatment.

## Key findings

- Pt(acac)₂(DMS) induces prolonged cytotoxicity in U251 cells without harming astrocytes.
- The compound causes mitochondrial dysfunction and modulates autophagy in glioblastoma cells.
- It shows potential to overcome cisplatin's limitations like toxicity and resistance.

## Abstract

Glioblastoma stands as the deadliest primary brain malignancy in adults, primarily due to its resistance to conventional treatments and the restrictive nature of the blood–brain barrier (BBB). Cisplatin (CDDP), a widely used chemotherapeutic, demonstrates limited efficacy against glioblastoma owing to systemic toxicity and insufficient BBB penetration. To overcome these hurdles, we tested the platinum(II) complex [Pt(O,O′-acac)(γ-acac)(DMS)], indicated as Pt(acac)₂(DMS), known for its improved lipophilicity, ability to disrupt mitochondrial function, and reduced neurotoxic profile. Compared to CDDP, Pt(acac)₂(DMS) induced a targeted and prolonged cytotoxic response in U251 glioblastoma cells, promoting mitochondrial dysfunction, cell cycle arrest, and modulation of autophagy, while sparing primary human astrocytes. Our findings indicate that Pt(acac)₂(DMS) may overcome key limitations of cisplatin, including toxicity issues and resistance associated with autophagic adaptation, highlighting its promise as a potential therapeutic candidate for glioblastoma treatment.