Background: Glioblastoma multiforme (GBM) is the most aggressive and malignant primary
brain tumor characterized by rapid growth and extensive infiltration to neighboring normal brain
parenchyma, which contribute to tumor recurrence and poor prognosis. Myricetin is a natural flavonoid
with potent anti-oxidant, anti-inflammatory and anti-cancer activities, which may serve as a potential
and harmless agent for GBM treatment.
Methods: To investigate the anti-glioblastoma effects of myricetin, GBM cells were treated with
myricetin alone or in combination with temozolomide. Its effects on GBM cell motility and cytoskeletal
structures including lamellipodia, focal adhesions and membrane ruffles were also evaluated.
Results: We showed that myricetin alone inhibited glioblastoma U-87 MG cell proliferation, migration
and invasion, whereas combination of myricetin and temozolomide did not exhibit any synergistic effect.
The inhibitory effect on GBM cell proliferation is independent of PTEN status. Moreover,
myricetin showed less cytotoxicity to normal astrocytes than GBM cells. Formation of lamellipodia,
focal adhesions, membrane ruffles and vasculogenic mimicry were blocked by myricetin, and phosphorylation
of ROCK2, paxillin and cortactin was suppressed. In addition, myricetin could inhibit
PI3K/Akt and JNK signaling, and bind to a series of kinases and scaffold proteins including PI3K
catalytic isoforms (p110α, p110β and p110δ), PDK1, JNK, c-Jun, ROCK2, paxillin, vinculin and VEcadherin.
Conclusions: In conclusion, myricetin is a multi-targeted drug that has potent anti-migratory and antiinvasive
effects on GBM cells, and suppresses formation of lamellipodia and focal adhesions, suggesting
that it may serve as an alternative option for GBM treatment.