Chang Jenq-Sheng, Kuo Hsiang-Ping, Chang Ke Liang B, Kong Zwe-Ling
Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.
PLoS One. 2015 Sep 1;10(9):e0136782. doi: 10.1371/journal.pone.0136782. eCollection 2015.
Antrodia camphorata is a well-known medicinal mushroom in Taiwan and has been studied for decades, especially with focus on anti-cancer activity. Polysaccharides are the major bioactive compounds reported with anti-cancer activity, but the debates on how they target cells still remain. Research addressing the encapsulation of polysaccharides from A. camphorata extract (ACE) to enhance anti-cancer activity is rare. In this study, ACE polysaccharides were nano-encapsulated in chitosan-silica and silica (expressed as ACE/CS and ACE/S, respectively) to evaluate the apoptosis effect on a hepatoma cell line (Hep G2). The results showed that ACE polysaccharides, ACE/CS and ACE/S all could damage the Hep G2 cell membrane and cause cell death, especially in the ACE/CS group. In apoptosis assays, DNA fragmentation and sub-G1 phase populations were increased, and the mitochondrial membrane potential decreased significantly after treatments. ACE/CS and ACE/S could also increase reactive oxygen species (ROS) generation, induce Fas/APO-1 (apoptosis antigen 1) expression and elevate the proteolytic activities of caspase-3, caspase-8 and caspase-9 in Hep G2 cells. Unsurprisingly, ACE/CS induced a similar apoptosis mechanism at a lower dosage (ACE polysaccharides = 13.2 μg/mL) than those of ACE/S (ACE polysaccharides = 21.2 μg/mL) and ACE polysaccharides (25 μg/mL). Therefore, the encapsulation of ACE polysaccharides by chitosan-silica nanoparticles may provide a viable approach for enhancing anti-tumor efficacy in liver cancer cells.
樟芝是台湾一种著名的药用真菌,已经研究了几十年,尤其侧重于抗癌活性。多糖是报道具有抗癌活性的主要生物活性化合物,但关于它们如何靶向细胞的争论仍然存在。针对从樟芝提取物(ACE)中提取的多糖进行包封以增强抗癌活性的研究很少。在本研究中,将ACE多糖纳米包封在壳聚糖-二氧化硅和二氧化硅中(分别表示为ACE/CS和ACE/S),以评估对肝癌细胞系(Hep G2)的凋亡作用。结果表明,ACE多糖、ACE/CS和ACE/S均能损伤Hep G2细胞膜并导致细胞死亡,尤其是在ACE/CS组。在凋亡分析中,处理后DNA片段化和亚G1期细胞群增加,线粒体膜电位显著降低。ACE/CS和ACE/S还可增加活性氧(ROS)的产生,诱导Fas/APO-1(凋亡抗原1)表达,并提高Hep G2细胞中caspase-3、caspase-8和caspase-9的蛋白水解活性。不出所料,ACE/CS在比ACE/S(ACE多糖=21.2μg/mL)和ACE多糖(25μg/mL)更低的剂量(ACE多糖=13.2μg/mL)下诱导了类似的凋亡机制。因此,壳聚糖-二氧化硅纳米颗粒对ACE多糖的包封可能为提高肝癌细胞的抗肿瘤疗效提供一种可行的方法。