College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China.
Nutrients. 2018 Aug 26;10(9):1170. doi: 10.3390/nu10091170.
Melanoma is a malignant tumor that begins in the melanocyte and has the highest mortality rate among all cutaneous tumors. Chinese propolis (CP) has been shown to have a potent antitumor effect against various cancers. In this study, we uncovered the combined effects of antiproliferation and anti-inflammation of CP on suppressing the progression of human melanoma cell line A375. We evaluated the alterations of protein expression after CP treatment by Western blot. After CP treatment, A375 cells underwent intrinsic apoptosis and cell cycle arrest. Furthermore, we found that CP suppressed inflammation in A375 cells. NLRP1 (NLR family pyrin domain containing 1), confirmed as a proinflammatory protein in melanoma progression, was downregulated significantly by CP, as were the NLRP1-related caspase activation and recruitment domains (CARD) proteins, including caspase-1 and caspase-4. Additionally, decreasing mRNA levels of , , and further proved the negative regulation of CP on the melanoma inflammatory environment. We also discovered that CP induced autophagy in A375 cells. Interestingly, inhibiting autophagy in CP-treated cells diminished its antitumor effect, suggesting that the autophagy was attributed to CP-induced apoptosis. Collectively, CP is a promising candidate for drug development for melanoma therapy.
黑色素瘤是一种起源于黑素细胞的恶性肿瘤,其死亡率在所有皮肤肿瘤中最高。中国蜂胶(CP)已被证明对多种癌症具有强大的抗肿瘤作用。在这项研究中,我们揭示了 CP 对人黑色素瘤细胞系 A375 的增殖抑制和抗炎的协同作用。我们通过 Western blot 评估了 CP 处理后蛋白表达的变化。CP 处理后,A375 细胞发生内在凋亡和细胞周期阻滞。此外,我们发现 CP 抑制了 A375 细胞的炎症反应。NLRP1(富含 NACHT、LRR 和 PYD 结构域的蛋白 1)被证实是黑色素瘤进展中的一种促炎蛋白,CP 显著下调了其表达,NLRP1 相关半胱天冬酶激活和募集结构域(CARD)蛋白,包括半胱天冬酶-1 和半胱天冬酶-4,也下调了。此外, 、 和 的 mRNA 水平降低进一步证明了 CP 对黑色素瘤炎症微环境的负调控作用。我们还发现 CP 诱导了 A375 细胞自噬。有趣的是,抑制 CP 处理细胞中的自噬会减弱其抗肿瘤作用,表明自噬是 CP 诱导凋亡的原因。综上所述,CP 是一种很有前途的黑色素瘤治疗药物开发候选物。