The effect of temozolomide on Hsp60 and Hsp70 expression in extracellular vesicles derived from U87MG glioma cells

Pekmez M., Kılcı C.

TURKISH JOURNAL OF BIOCHEMISTRY-TURK BIYOKIMYA DERGISI, cilt.11, sa.4, ss.1-11, 2021 (SCI-Expanded)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 11 Sayı: 4
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1515/tjb-2021-0111
  • Dergi Adı: TURKISH JOURNAL OF BIOCHEMISTRY-TURK BIYOKIMYA DERGISI
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE, Food Science & Technology Abstracts, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.1-11
  • İstanbul Üniversitesi Adresli: Evet

Özet

Objectives: Temozolomide (TMZ) is an effective drug for
glioblastoma multiforme (GBM), but the mechanism underlyingTMZ
resistance is poorly understood. Newevidence
has revealed that the release of heat shock proteins (Hsps)
derived from extracellular vesicles (EVs) play an important
role in cancer progression by modulating tumor microenvironment
and cellular cross-talk. This study aims to evaluate
the effects of TMZ on the expression of EV-derived and
cellular Hsps and cell motility in U87MG human glioblastoma
cell line.
Methods: Glial-EVs were isolated from the culture medium
and characterized by SEM and immunoblotting. The
effect of TMZ treatments (25, 200 and 750 μM) on cell proliferation
(MTT assay), migration (scratch assay), and
Hsp60 and Hsp70 levels (immunoblotting) were evaluated.
Results: TMZ treatments led to an increase in intracellular
Hsp70 while decreasing EV-derived Hsp70. Cellular Hsp60
level was elevated at the low dose of TMZ, but it reduced at
higher TMZ concentrations. Hsp60 was also decreased in
EVs secreted from TMZ-treated cells. Besides, TMZ treatment
reduced the proliferation and migration of glioma
cells in a dose-dependent manner.

Conclusions: Our results suggest that TMZ has the potential
to target both EV-derived and cellular Hsps for GBM
treatment, thus it may reduce cell motility.