Cucurbitacin B inhibits growth, arrests the cell cycle, and potentiates antiproliferative efficacy of cisplatin in cutaneous squamous cell carcinoma cell lines
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Date
2010
Authors
Chen, Weikai
Leiter, Amanda
Yin, Dong
Meiring, Muriel
Louw, Vernon J.
Koeffler, H. Phillip
Journal Title
Journal ISSN
Volume Title
Publisher
Spandidos Publications
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 4x10-7
-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.
Description
Keywords
Cucurbitacin B, Cell cycle, Cisplatin, Cutaneous squamous cell carcinoma, Skin -- Cancer, Squamous cell carcinoma
Citation
Chen, W., Leiter, A., Yin, D., Meiring, M., Louw, V. J., & Koeffler, H. P. (2010). Cucurbitacin B inhibits growth, arrests the cell cycle, and potentiates antiproliferative efficacy of cisplatin in cutaneous squamous cell carcinoma cell lines. International journal of oncology, 37(3), 737-743.