Jasinski P et al. - In a study to investigate the effects of enzastaurin and gamma irradiation on protein kinase C (PKC) activity in MCF-7 human breast cancer cells in vitro and in vivo, it was found that enzastaurin has a radiosensitising effect on MCF-7 human xenograft tumours through reversal of anti-apoptotic activation of PKC isoforms Methods
The study investigated the effects of enzastaurin and gamma irradiation on PKC activity in MCF-7 human breast cancer cells in vitro and in vivo
Results
Enzastaurin (5 μM) in combination with irradiation (2–8 Gy) produced a synergistic decline in MCF-7 clonogenic cell survival
Analysis of MCF-7 cells stained with Annexin V and 7-aminoactinomycin D showed a dose-dependent increase in apoptosis in response to enzastaurin (3, 5 and 7 μM) and irradiation (10 Gy) vs irradiation alone
This pro-apoptotic effect was confirmed by increases in caspase-3 and -9 activity
In a MCF-7 xenograft model, irradiation with 25 Gy increased PKC-α activity by 2.5-fold compared to untreated controls, whereas PKC-ε and -βII activity was increased by 1.8-fold
Radiation-induced activation of all 3 anti-apoptotic isoforms of PKC was reversed by pre-treatment with enzastaurin (75 mg/kg, twice daily for 3 days)
See all
