Rajan Thangavelu Soundara, De Nicola Gina Rosalinda, Iori Renato, Rollin Patrick, Bramanti Placido, Mazzon Emanuela
IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, contrada Casazza, 98124 Messina, Italy.
Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria, Centro di Ricerca per le Colture Industriali (CREA-CIN), Via Di Corticella 133, Bologna 40128, Italy.
Fitoterapia. 2016 Apr;110:1-7. doi: 10.1016/j.fitote.2016.02.007. Epub 2016 Feb 13.
Isothiocyanates (ITCs) released from their glucosinolate precursors have been shown to inhibit tumorigenesis and they have received significant attention as potential chemotherapeutic agents against cancer. Astrocytoma grade IV is the most frequent and most malignant primary brain tumor in adults without any curative treatment. New therapeutic drugs are therefore urgently required. In the present study, we investigated the in vitro antitumor activity of the glycosylated isothiocyanate moringin [4-(α-l-rhamnopyranosyloxy)benzyl isothiocyanate] produced from quantitative myrosinase-induced hydrolysis of glucomoringin (GMG) under neutral pH value. We have evaluated the potency of moringin on apoptosis induction and cell death in human astrocytoma grade IV CCF-STTG1 cells. Moringin showed to be effective in inducing apoptosis through p53 and Bax activation and Bcl-2 inhibition. In addition, oxidative stress related Nrf2 transcription factor and its upstream regulator CK2 alpha expressions were modulated at higher doses, which indicated the involvement of oxidative stress-mediated apoptosis induced by moringin. Moreover, significant reduction in 5S rRNA was noticed with moringin treatment. Our in vitro results demonstrated the antitumor efficacy of moringin derived from myrosinase-hydrolysis of GMG in human malignant astrocytoma cells.
从其硫代葡萄糖苷前体释放的异硫氰酸盐(ITCs)已被证明可抑制肿瘤发生,并且作为潜在的抗癌化疗药物受到了广泛关注。IV级星形细胞瘤是成人中最常见、最恶性的原发性脑肿瘤,目前尚无治愈性治疗方法。因此,迫切需要新的治疗药物。在本研究中,我们研究了在中性pH值下,由定量的黑芥子酶诱导水解葡糖萝卜硫苷(GMG)产生的糖基化异硫氰酸盐萝卜硫素[4-(α-L-鼠李糖吡喃糖氧基)苄基异硫氰酸盐]的体外抗肿瘤活性。我们评估了萝卜硫素对人IV级星形细胞瘤CCF-STTG1细胞凋亡诱导和细胞死亡的作用。萝卜硫素通过激活p53和Bax以及抑制Bcl-2有效诱导细胞凋亡。此外,在较高剂量下,与氧化应激相关的Nrf2转录因子及其上游调节因子CK2α的表达受到调节,这表明萝卜硫素诱导的氧化应激介导的细胞凋亡参与其中。此外,萝卜硫素处理后5S rRNA显著减少。我们的体外研究结果证明了GMG经黑芥子酶水解产生的萝卜硫素对人恶性星形细胞瘤细胞的抗肿瘤疗效。