Department of Experimental Medicine, University of Rome, Sapienza, Rome, Italy.
Front Biosci (Landmark Ed). 2012 Jan 1;17(2):498-508. doi: 10.2741/3940.
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.
源自间充质的恶性肿瘤，如横纹肌肉瘤和骨肉瘤，是具有不良预后的高度侵袭性儿科恶性肿瘤。事实上，化疗的初始反应后是化疗耐药。二烯丙基二硫化物（DADS）、白藜芦醇（RES）和姜黄素（CUR）是具有抗肿瘤活性的膳食化学预防植物化学物质，它们已被报道对横纹肌肉瘤和骨肉瘤细胞具有抗肿瘤活性。在这项研究中，我们评估了与单一化合物相比，DADS+RES、DADS+CUR 和 RES+CUR 的组合是否会增强其对恶性横纹肌样（SJ-RH4、RD/18）或骨肉瘤（Saos-2）细胞系的抗肿瘤潜力。通过流式细胞术分析和激活的 caspase-3 标记，我们证明 CUR 诱导横纹肌肉瘤和骨肉瘤细胞凋亡，当 CUR 与 RES 或 DADS 联合使用时，这种作用会增强。此外，我们还探讨了这些化合物单独或联合使用对参与细胞凋亡和生长的信号转导途径的影响，并表明在横纹肌肉瘤细胞中，CUR 单独或联合使用的凋亡作用独立于 p53 活性。我们的研究结果表明，CUR 和基于 CUR 的组合可能与治疗 p53 缺失的癌症有关，这些癌症通常不受常规化疗或放疗的影响。
