Abstract

Securinega virosa Roxb (Ex Willd) is a commonly used medicinal plant in the management of inflammatory conditions and tumor in African traditional medicine. In this study, the effects of the crude methanol root bark extract and its fractions were evaluated on the survival of Glioblastoma mutiforme (GBM) tumor cells (U-1242) in vitro. The effects of the crude extract and its fractions on epidermal growth factor receptor (EGFR) which is overexpressed in about 40 to 60% of GBM patients were also evaluated. Their activities on the phosphorylation of downstream mediators of tumor cell growth and proliferation such as Akt and mitogen activated protein kinase (MAPK) were also studied using western blot analysis. The crude methanol root bark extract and the various fractions; namely, residual aqueous, n-butanol soluble and chloroform fractions significantly (P < 0.0001) and concentration-dependently (31.25 to 500 µg/ml) reduced tumor cell growth with IC₅₀ ranging from 4.87 µg/ml for the chloroform fraction to 58.5 µg/ml for the butanol fraction. The crude methanol root bark extract and the residual aqueous fraction blocked EGFR phosphorylation at tyrosine 1068 and 1045 sites. They also significantly inhibited platelet derived growth factor receptor (PDGFR) phosphorylation. In addition, crude methanol root as well as the residual aqueous and butanol fractions blocked phorbol myristate acetate (PMA) and PDGFR-induced transactivation of the EGFR at tyrosine 1068. Similarly, the crude methanol root bark extract reduced the phosphorylation of MAPK. In contrast, Akt was not significantly altered. These findings showed that the crude methanol root bark extract of Securinega virosa possesses significant activity against GBM cells which may be mediated partly via EGFR and some other downstream mediators of cell survival.

Key words: Securinega virosa, glioblastoma multiforme, epidermal growth factor receptor (EGFR), mitogen activated protein kinase (MAPK).