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 | Weikai Chen, Amanda Leiter, Dong Yin, Muriel Meiring, Vernon J Louw, H Phillip Koeffler |
Journal | International journal of oncology
(Int J Oncol)
Vol. 37
Issue 3
Pg. 737-43
(Sep 2010)
ISSN: 1791-2423 [Electronic] Greece |
PMID | 20664943
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Triterpenes
- cucurbitacin B
- Cisplatin
|
Topics |
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Apoptosis
(drug effects)
- Carcinoma, Squamous Cell
(drug therapy, pathology)
- Cell Cycle
(drug effects)
- Cell Growth Processes
(drug effects)
- Cell Line, Tumor
- Cell Membrane
(drug effects)
- Cisplatin
(administration & dosage, pharmacology)
- Drug Synergism
- Humans
- Skin Neoplasms
(drug therapy, pathology)
- Triterpenes
(administration & dosage, pharmacology)
|