Resveratrol and diallyl disulfide enhance curcumin-induced sarcoma cell apoptosis.
Malignant tumors of mesenchimal origin such as rhabdomyosarcoma and osteosarcoma are highly aggressive pedriatic malignancies with a poor prognosis. Indeed, the initial response to chemotherapy is followed by chemoresistance. Diallyl disulfide (DADS), resveratrol (RES) and curcumin (CUR) are dietary chemopreventive phytochemicals which have been reported to have antineoplastic activity on rhabdomyosarcoma and osteosarcoma cells as single drugs. In this study we evaluated whether, as compared to the single compounds, the combination of DADS+RES, DADS+CUR and RES+CUR resulted in an enhancement of their antitumor potential on malignant rhabdoid (SJ-RH4, RD/18) or osteosarcoma (Saos-2) cell lines. Through FACS analysis and activated caspase-3 labeling we demonstrate that CUR induces apoptosis of rabdomyosarcoma and osteosarcoma cells and that this effect is potentiated when CUR is combined with RES or DADS. Further, we explored the effects of the compounds, alone or in combination, on signal transduction pathways involved in apoptosis and growth of cancer cells and show that in rhabdomyosarcoma cells the apoptotic effect of CUR, either alone or in combination, is independent of p53 activity. Our findings suggest that CUR and CUR-based combinations may have relevance for the treatment of p53-deficient cancers, which are often unaffected by conventional chemotherapies or radiotherapy.
Department of Experimental Medicine, University of Rome, Sapienza, Rome, Italy.
Laura
L
Masuelli
Laura
L
Marzocchella
Chiara
C
Focaccetti
Ilaria
I
Tresoldi
Camilla
C
Palumbo
Valerio
V
Izzi
Monica
M
Benvenuto
Massimo
M
Fantini
Florigio
F
Lista
Umberto
U
Tarantino
Andrea
A
Modesti
Fabio
F
Galvano
Roberto
R
Bei
D000498:Allyl Compounds / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage*; D004220:Disulfides / Q000008:administration & dosage*; D004357:Drug Synergism; D006801:Humans; D000077185:Resveratrol; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000498:Allyl Compounds; D000972:Antineoplastic Agents, Phytogenic; D004220:Disulfides; D013267:Stilbenes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C028009:diallyl disulfide; D003474:Curcumin; D000077185:Resveratrol