The effect of silibinin in enhancing toxicity of temozolomide and etoposide in p53 and PTEN-mutated resistant glioma cell lines.
Glioblastoma multiforme (GBM) is an intractable brain tumor, associated with poor prognosis and low survival rate. Combination therapy such as surgery, radiotherapy and temozolomide is considered standard in overcoming this aggressive cancer, despite poor prognosis. There is a need to identify potential agents, which may augment the chemotherapeutic effects of standard drugs such as temozolomide. In this project, we evaluated the effects of silibinin, a natural plant component of milk thistle seeds, to potentiate toxic effects of chemotherapy drugs such as temozolomide, etoposide and irinotecan on LN229, U87 and A172 (P53 and phosphatase and tensin homolog (PTEN) -tumor suppressor-mutated) glioma cell lines. Data from this work suggest that silibinin was effective in potentiating the cytotoxic efficacy of temozolomide in LN229, U87 and A172 cells. While silibinin reduced survivin protein expression only in LN229 cells, its ability to potentiate cytotoxicity of chemo therapy drugs occurred irrespective of survivin protein levels. The data also demonstrated that silibinin potentiated the effect of etoposide and but not irinotecan in LN229 cells. Future research will be required to evaluate the in vivo efficacy of silibinin to delineate its mechanism of action and its ability to cross the blood-brain barrier.
Department of Biology, Florida A&M University, Tallahassee, FL, U.S.A.
Rashid
R
Elhag
College of Pharmacy & Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, U.S.A.
Elizabeth A
EA
Mazzio
College of Pharmacy & Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, U.S.A. karam.soliman@famu.edu.
Karam F A
KF
Soliman
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology; D016158:Genes, p53; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis / Q000502:physiology; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D000077022:Survivin; D000077204:Temozolomide
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012838:Silymarin; D000077022:Survivin; D000077385:Silybin; D005047:Etoposide; D003606:Dacarbazine; D051059:PTEN Phosphohydrolase; D000077204:Temozolomide
Glioblastoma; milk thistle; natural compounds; silibinin; temozolomide