Cell motility and resistance to apoptosis characterize
glioblastoma multiforme growth and
malignancy.
Narciclasine, a plant growth modulator, could represent a powerful new weapon targeting the Achilles' heel of
glioblastoma multiforme and may offer the potential to better combat these devastating
malignancies. The in vitro effects of
narciclasine on cell proliferation, morphology, actin cytoskeleton organization, and the Rho/
Rho kinase/
LIM kinase/
cofilin pathway and its antitumor activity in vivo have been determined in models of human
glioblastoma multiforme.
Narciclasine impairs
glioblastoma multiforme growth by markedly decreasing mitotic rates without inducing apoptosis. The compound also modulates the Rho/
Rho kinase/
LIM kinase/
cofilin signaling pathway, greatly increasing
GTPase RhoA activity as well as inducing actin stress fiber formation in a RhoA-dependent manner. Lastly, the treatment of human
glioblastoma multiforme orthotopic xenograft- bearing mice with nontoxic doses of
narciclasine significantly increased their survival.
Narciclasine antitumor effects were of the same magnitude as those of
temozolomide, the drug associated with the highest therapeutic benefits in treating
glioblastoma multiforme patients. Our results show for the first time that
narciclasine, a plant growth modulator, activates Rho and stress fibers in
glioblastoma multiforme cells and significantly increases the survival of human
glioblastoma multiforme preclinical models. This statement is made despite the recognition that to date, irrespective of treatment, no single
glioblastoma multiforme patient has been cured.