TY - JOUR
T1 - Cucurbitacin B inhibits growth, arrests the cell cycle, and potentiates antiproliferative efficacy of cisplatin in cutaneous squamous cell carcinoma cell lines
AU - Chen, Weikai
AU - Leiter, Amanda
AU - Dong, Yin
AU - Meiring, Muriel
AU - Louw, Vernon J.
AU - Koeffler, H. Phillip
PY - 2010/9
Y1 - 2010/9
N2 - 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 (ED 50) of the CSCC cell lines (SRB1, SRB12, SCC13, COLO16) in liquid culture at 4×10 -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.
AB - 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 (ED 50) of the CSCC cell lines (SRB1, SRB12, SCC13, COLO16) in liquid culture at 4×10 -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.
KW - Cell cycle
KW - Cisplatin
KW - Cucurbitacin B
KW - Cutaneous squamous cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=77956532375&partnerID=8YFLogxK
U2 - 10.3892/ijo-00000723
DO - 10.3892/ijo-00000723
M3 - Article
C2 - 20664943
AN - SCOPUS:77956532375
SN - 1019-6439
VL - 37
SP - 737
EP - 743
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 3
ER -