p53 inactivation sensitizes U87MG
astrocytic glioma cells to
1,3-bis(2-chloroethyl)-1-nitrosourea (
BCNU) and
temozolomide (TMZ), drugs used clinically to treat high-grade
astrocytomas. In this report, we examined the effect of p53 inactivation on the chemosensitivity of two additional human
astrocytic glioma cell lines, D54 and A172, in order to assess whether sensitization is a general property of astrocytic
tumor cells. Compared to control cells with intact p53 function, derived lines in which p53 was inactivated displayed significantly reduced clonogenic survival after exposure to
BCNU and TMZ. Sensitization to both
BCNU and TMZ was associated with failure of p21(WAF1) induction, lack of a sustained G2 cell cycle arrest and significant
tumor cell death. These findings suggest that enhanced sensitivity to
BCNU and TMZ is a general property of human
astrocytic glioma cells in which p53 was disrupted. In contrast, p53 inactivation rendered D54 and U87MG cells significantly more resistant to cis-dichlorodiamminoplatinum (CDDP), another chemotherapeutic to which high-grade
astrocytomas sometimes respond. These results indicate that p53 status influences the chemosensitivity of
astrocytic glioma cells in a
drug-type specific manner, a finding that may have implications for the selection of
drug treatments for patients with
astrocytic gliomas.