title: Cucurbitacin B inhibits growth, arrests the cell cycle, and potentiates antiproliferative efficacy of cisplatin in cutaneous squamous cell carcinoma cell lines.
abstract: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with a substantial risk of metastasis which causes clinical treatment failure. This study investigated the anti-CSCC effects of a triterpenoid compound, Cucurbitacin B (CuB). Dose-response studies showed that CuB inhibited 50% growth (ED50) of the CSCC cell lines (SRB1, SRB12, SCC13, COLO16) in liquid culture at 4 x 10(-7)-10(-5) M. Soft-agar assays demonstrated that nearly all of the CSCC clonogenic cells were inhibited at 10(-7) M CuB. FACS analysis found that the compound (10(-7) M, 48 h) caused G2/M arrest. The CSCC cells underwent profound morphologic changes within 60 min after exposure to CuB (10(-7) M), rounding up and losing their pseudopodia. CuB (10(-7) M) caused prominent multinucleation of the cells after they were pulse-exposed (24 h) to the drug, washed and cultured in normal medium for an additional 24 h. The drug (10(-8)-10(-6) M, 3-24 h) decreased levels of CDC2 and cyclin B1 in SRB1 and SRB12 cell lines as seen by Western blot analysis. Migration of SRB1 and SRB12 cells was inhibited by 10(-7) M CuB. Interestingly, CuB synergistically potentiated the anti-proliferative effect of cisplatin in CSCC. In summary, CuB has a prominent anti-proliferative activity on CSCC cells. In vivo studies and clinical trials of this drug should be pursued in CSCC.
authors.affiliation: Department of Hematology and Cell Biology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9301, Free State, South Africa.
authors.forename: Weikai
authors.initials: W
authors.lastname: Chen
authors.forename: Amanda
authors.initials: A
authors.lastname: Leiter
authors.forename: Dong
authors.initials: D
authors.lastname: Yin
authors.forename: Muriel
authors.initials: M
authors.lastname: Meiring
authors.forename: Vernon J
authors.initials: VJ
authors.lastname: Louw
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014315:Triterpenes; C041246:cucurbitacin B; D002945:Cisplatin