Apoptosis induction by 4-nerolidylcatechol in melanoma cell lines.
Pothomorphe umbellata, a native Brazilian plant, is popularly known to be effective in the treatment of skin lesions. This benefit is attributed to 4-nerolidylcatechol (4-NC), a compound extracted from P. umbellata. Since melanomas show prominent resistance to apoptosis and exhibit extreme chemoresistance to multiple forms of therapy, novel compounds addressing induction of cell death are worth investigating. Here, we evaluated effects on cell cycle progression and possible cytotoxic activity of 4-NC in melanoma cell lines as well as human dermal fibroblasts. Inhibitory effects on cell invasion and MMP activity were also investigated. 4-NC showed cytotoxic activity for all melanoma cell lines tested (IC50=20-40 microM, 24h for tumoral cell lines; IC50=50 microM for fibroblast cell line) associated with its capacity to induce apoptosis. Furthermore, this is the first time that 4-NC is described as an inhibitor of cell invasiveness, due mainly to a G1 cell cycle arrest and inhibition of MMP-2 activity in melanoma cell lines.
Brohem
C A
CA
Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, Brazil.
Sawada
T C H
TC
Massaro
R R
RR
Almeida
R L
RL
Rivelli
D P
DP
Ropke
C D
CD
da Silva
V V
VV
de Lima
T M
TM
Curi
R
R
Barros
S B M
SB
Maria-Engler
S S
SS
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002396:Catechols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D026321:Piperaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
C110583:4-nerolidylcatechol; D000970:Antineoplastic Agents; D002396:Catechols; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D020778:Matrix Metalloproteinase 2