Lupeol inhibits growth of highly aggressive human metastatic melanoma cells in vitro and in vivo by inducing apoptosis.
OBJECTIVE
Poor prognosis of metastatic melanoma mandates the development of novel strategies for its treatment and prevention. In this study, the effect of lupeol, a diet-based triterpene, was determined on the growth and tumorigenicity of human melanoma cells in vitro and in vivo.


METHODS
Normal human melanocytes, and human metastatic (451Lu) and nonmetastatic (WM35) cells were treated with lupeol; its effect on growth, proliferation, and apoptosis were evaluated. Further athymic nude mice bearing 451Lu cell-originated tumors were administered with lupeol thrice a week, and its effect on tumor growth and surrogate biomarkers was evaluated.


RESULTS
Lupeol significantly decreased the viability of 451Lu and WM35 melanoma cells but had only a marginal effect on normal human melanocyte cells at similar doses. Lupeol treatment of 451Lu cells caused (a) G(1)-S phase cell cycle arrest and apoptosis; (b) down-regulation of Bcl2 and up-regulation of Bax; (c) activation of caspase-3 and induction of poly(ADP)ribose polymerase cleavage; (d) decreased expression of cyclin D1, cyclin D2, and cdk2; and (e) increased expression of p21 protein. Next, lupeol significantly reduced 451Lu tumor growth in athymic nude mice and modulated the expression of proliferation markers, apoptotic markers, and cell cycle regulatory molecules in tumor xenografts.


CONCLUSIONS
Our findings showed the anticancer efficacy of lupeol with mechanistic rationale against metastatic human melanoma cells. We suggest that lupeol, alone or as an adjuvant to current therapies, could be useful for the management of human melanoma.
Saleem
Mohammad
M
Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Maddodi
Nityanand
N
Abu Zaid
Mohammad
M
Khan
Naghma
N
bin Hafeez
Bilal
B
Asim
Mohammad
M
Suh
Yewseok
Y
Yun
Jung-Mi
JM
Setaluri
Vijayasaradhi
V
Mukhtar
Hasan
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000094042:Lupanes
D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C010480:lupeol; D000094042:Lupanes