Enhancing melanoma treatment with resveratrol.
BACKGROUND
Resveratrol (RESV) is a naturally occurring compound that possesses anti-cancer capabilities. The goal of this study was to evaluate the potential of RESV as an adjunct to chemotherapy in melanoma treatment.


METHODS
The in vitro and in vivo cytotoxic activity of RESV with or without chemotherapy was tested using cellular assays and a xenograft model. Two Duke melanoma cell lines (DM738, DM443) were used for both in vivo and in vitro experiments, and two nonmalignant human fibroblast lines (NHDF, HS68) were used for in vitro cellular assays. Xenografts were randomized to treatment arms and tumors measured to evaluate response. Results were analyzed using a Student's t-test and ANOVA. Western blots were performed on in vivo tissue.


RESULTS
In vitro RESV significantly decreased melanoma cell viability in all lines tested (all P < 0.0001). Treatment of fibroblast cell lines revealed that RESV selectively spared NHDF and HS68 cells compared with its cytotoxic effects on melanoma cells (P < 0.0001). Treatment of malignant cells with 50 μM RESV and temozolomide (TMZ) for 72 h significantly enhanced cytotoxicity compared with treatment with TMZ alone (P < 0.0001). In vivo, however, there was no significant difference between any treatment arms (P = 0.65).


CONCLUSIONS
RESV shows promise as a novel therapeutic in the management of melanoma for its selective anti-tumor activity in vitro. Translating in vitro results to in vivo models has proven difficult. Barriers thought to prevent such translation are identified, and a rationale for overcoming them is discussed.
Osmond
Gregory W
GW
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Augustine
Christina K
CK
Zipfel
Patricia A
PA
Padussis
James
J
Tyler
Douglas S
DS
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008558:Melphalan / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D000077185:Resveratrol; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013267:Stilbenes / Q000627:therapeutic use*; D000077204:Temozolomide; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D013267:Stilbenes; D003606:Dacarbazine; D000077185:Resveratrol; D008558:Melphalan; D000077204:Temozolomide