Mechanism of Arctigenin-Induced Specific Cytotoxicity against Human Hepatocellular Carcinoma Cell Lines: Hep G2 and SMMC7721

Abstract

Arctigenin (ARG) has been previously reported to exert high biological activities including anti-inflammatory, antiviral and anticancer. In this study, the anti-tumor mechanism of ARG towards human hepatocellular carcinoma (HCC) was firstly investigated. We demonstrated that ARG could induce apoptosis in Hep G2 and SMMC7721 cells but not in normal hepatic cells, and its apoptotic effect on Hep G2 was stronger than that on SMMC7721. Furthermore, the following study showed that ARG treatment led to a loss in the mitochondrial out membrane potential, up-regulation of Bax, down-regulation of Bcl-2, a release of cytochrome c, caspase-9 and caspase-3 activation and a cleavage of poly (ADP-ribose) polymerase in both Hep G2 and SMMC7721 cells, suggesting ARG-induced apoptosis was associated with the mitochondria mediated pathway. Moreover, the activation of caspase-8 and the increased expression levels of Fas/FasL and TNF-α revealed that the Fas/FasL-related pathway was also involved in this process. Additionally, ARG induced apoptosis was accompanied by a deactivation of PI3K/p-Akt pathway, an accumulation of p53 protein and an inhibition of NF-κB nuclear translocation especially in Hep G2 cells, which might be the reason that Hep G2 was more sensitive than SMMC7721 cells to ARG treatment.

NFAT5 inhibits invasion and promotes apoptosis in hepatocellular carcinoma associated with osmolality

“…Next we observed that NFAT5 promotes apoptosis via regulating PARP-1, BAX and BCL-2, essential biomarkers of apoptosis. PARP-1 is the downstream of BAX/BCL-2 in apoptotic pathway [9,18]. PARP-1 has been demonstrated to contribute DNA base excision repair and maintenance of genomic stability [19].…”

“…Poly (ADP-ribose) polymerase 1 (PARP-1), BAX/BCL-2 are considered as great important biomarker of apoptosis. During apoptosis, PARP-1 is cleaved into an 85 kDa fragment, which has the real function to initiate downstream signals [9]. BAX is a protein leading to apoptosis while BCL-2 is a protein function as anti-apoptotic factor.…”

Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

“…Adriamycin (ARG) has been currently recognized as a multifunctional chemotherapeutic drug with anti-inflammatory, anti-viral, anti-cancer, and other functions [80]. The data from Lu et al [81] showed that apoptosis in HepG2 cells and Smmc7721 cells could be induced by Adriamycin via activation of the Caspase-8 signaling pathway, up-regulation of Fas/FasL expression, and increasing the secretion of TNF-alpha. The apoptotic effect of the former was significantly stronger than that of the latter.…”

Investigation of the profile of phenolic compounds in the leaves and stems of Pandiaka heudelotii using gas chromatography coupled with flame ionization detector

“…Caffeic acid increases collagen production, in addition to having antiaging, antioxidant, antimicrobial, antiatherosclerotic, antidiabetic, antitumor, anti-inflammatory, and photo-protective properties (Dhingra & Chhillar, 2012;Gugliucci, Bastos, Schulze, & Souza, 2009;Magnani, Isaac, Correa, & Salgado, 2014;Oksana et al, 2012). Studies have shown that arctigenin has antioxidant, antitumor, anti-inflammatory, antiviral, analgesic, neuroprotective, and memoryenhancing activities (Chakraborty & Borah, 2013;Du et al, 2016;Lu et al, 2015;Park, Hong, Moon, Kim, & Kim, 2011;Srivastava & Shukla, 2015;Zhu et al, 2013). Retusin is an antiemetic, antitumor, and psychoactive agent; and teas containing it are used as anti-inflammatory agents, analgesics, purgative, laxative, and cathartic (Chakrapani et al, 2013;Chapman et al, 2006).…”