Boccellino Mariarosaria, Ambrosio Pasqualina, Ballini Andrea, De Vito Danila, Scacco Salvatore, Cantore Stefania, Feola Antonia, Di Donato Marzia, Quagliuolo Lucio, Sciarra Antonella, Galasso Giovanni, Crocetto Felice, Imbimbo Ciro, Boffo Silvia, Di Zazzo Erika, Di Domenico Marina
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", 70124 Bari, Italy.
Cancers (Basel). 2022 Jul 9;14(14):3348. doi: 10.3390/cancers14143348.
A major challenge in the clinical management of prostate cancer (PC) is to inhibit tumor growth and prevent metastatic spreading. In recent years, considerable efforts have been made to discover new compounds useful for PC therapy, and promising advances in this field were reached. Drugs currently used in PC therapy frequently induce resistance and PC progresses toward metastatic castration-resistant forms (mCRPC), making it virtually incurable. Curcumin, a commercially available nutritional supplement, represents an attractive therapeutic agent for mCRPC patients. In the present study, we compared the effects of chemotherapeutic drugs such as docetaxel, paclitaxel, and cisplatin, to curcumin, on two PC cell lines displaying a different metastatic potential: DU145 (moderate metastatic potential) and PC-3 (high metastatic potential). Our results revealed a dose-dependent reduction of DU145 and PC-3 cell viability upon treatment with curcumin similar to chemotherapeutic agents (paclitaxel, cisplatin, and docetaxel). Furthermore, we explored the EGFR-mediated signaling effects on ERK activation in DU145 and PC-3 cells. Our results showed that DU145 and PC-3 cells overexpress EGFR, and the treatment with chemotherapeutic agents or curcumin reduced EGFR expression levels and ERK activation. Finally, chemotherapeutic agents and curcumin reduced the size of DU145 and PC-3 spheroids and have the potential to induce apoptosis and also in Matrigel. In conclusion, despite different studies being carried out to identify the potential synergistic curcumin combinations with chemopreventive/therapeutic efficacy for inhibiting PC growth, the results show the ability of curcumin used alone, or in combinatorial approaches, to impair the size and the viability of PC-derived spheroids.
前列腺癌(PC)临床管理中的一个主要挑战是抑制肿瘤生长并防止转移扩散。近年来,人们付出了巨大努力来发现可用于PC治疗的新化合物,并在该领域取得了有希望的进展。目前用于PC治疗的药物经常会诱导耐药性,PC会发展为转移性去势抵抗性形式(mCRPC),几乎无法治愈。姜黄素是一种市售的营养补充剂,对mCRPC患者来说是一种有吸引力的治疗药物。在本研究中,我们比较了多西他赛、紫杉醇和顺铂等化疗药物与姜黄素对两种具有不同转移潜能的PC细胞系的影响:DU145(中等转移潜能)和PC-3(高转移潜能)。我们的结果显示,与化疗药物(紫杉醇、顺铂和多西他赛)类似,用姜黄素处理后,DU145和PC-3细胞活力呈剂量依赖性降低。此外,我们探讨了EGFR介导的信号对DU145和PC-3细胞中ERK激活的影响。我们的结果表明,DU145和PC-3细胞过度表达EGFR,用化疗药物或姜黄素处理可降低EGFR表达水平和ERK激活。最后,化疗药物和姜黄素减小了DU145和PC-3球体的大小,并且有可能在基质胶中诱导细胞凋亡。总之,尽管已经进行了不同的研究来确定姜黄素与具有抑制PC生长的化学预防/治疗功效的潜在协同组合,但结果表明单独使用姜黄素或采用联合方法能够损害PC来源球体的大小和活力。