Zinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems

Aug 25, 2016Oncotarget

Zinc increases the cancer-killing effect of temozolomide in glioblastoma models

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Addition of zinc to temozolomide treatment resulted in a significant reduction in tumor volume in mice with glioblastoma.

In vitro analysis showed that zinc enhanced the cytotoxicity of temozolomide against glioblastoma cells.
This enhancement was associated with increased expression of proteins linked to cell death, including p21, PUMA, BAX, and Caspase-3.
A decrease in the growth fraction was observed, indicated by lower levels of ki67 and reduced colony formation.
In vivo results mirrored the in vitro findings, demonstrating a significant reduction in tumor size with concurrent zinc and temozolomide treatment compared to temozolomide alone.
Zinc may act as a potentiator of temozolomide therapy in glioblastoma patients.

AI simplified

Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most malignant brain cancer, glioblastoma multiforme (GBM). Unfortunately only a limited number of patients positively respond to it. It has been shown that zinc metal reestablishes chemosensitivity but this effect has not been tested with TMZ. Using both in vitro and in vivo experimental approaches, we investigated whether addition of zinc to TMZ enhances its cytotoxicity against GBM. In vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased with addition of zinc and this response was accompanied by an elevation of p21, PUMA, BAX and Caspase-3 expression and a decrease in growth fraction as manifested by low ki67 and lower colony formation. Analysis of GBM as intracranial xenografts in athymic mice and administration of concurrent TMZ and zinc yielded results consistent with those of the in vitro analyses. The co-treatment resulted in significant reduction in tumor volume in TMZ/zinc treated mice relative to treatment with TMZ alone. Our results suggest that zinc may serve as a potentiator of TMZ therapy in GBM patients.

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text ↗

Zinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief