br Introduction Hepatocellular carcinoma HCC is an aggressiv

Introduction Hepatocellular carcinoma (HCC) is an aggressive and malignant cancer detected in clinical practice, as it is the third key reason of tumor-related deaths worldwide, with > 800, 000 mortalities every year (Torre et al., 2015). Current treatments for HCC are surgical therapy, liver transplantation, and traditional chemotherapy (Cui et al., 2016). Surgical treatment is preferred for HCC, but most patients with liver cancer have lost the best years for surgery when diagnosed and only undergo chemotherapy. However most patients are not sensitive to chemotherapy, which does not usually improve patient quality of life (Fitzmorris et al., 2015). Therefore, it is urgently needed to develop new drugs and therapeutic strategies for patients of advanced HCC. Natural products have been widely used and have become important in the last few decades for developing various cytotoxic drugs (Newman and Cragg, 2012). Traditional Chinese medicine (TCM) has been widely applied to prevent, diagnose, and cure many diseases in China and other Asian countries for over 3000 years (Tian et al., 2017). Discovering safe and effective cytotoxic compounds from TCMs is presently a hot research highlights, and many effective constituents isolated from TCMs have significant toxicity against cancer Hordenine synthesis (Luo et al., 2011). However, TCMs comprise a typical complex chemical system, and their effects on the body comprise multiple organs, roles, and targets; thus, studying their mechanisms of action is very difficult (Zhou et al., 2015). As proteins are the major executers of life activities, the proteomic analysis directly reflects proteins expression. Proteomics is a effective tool to study biological systems (Kim et al., 2016) and a powerful method to find the molecular targets of TCM and investigate the underlying mechanism and potential TCM drug markers of diseases. Besides, proteomics converges with TCM based on holistic and systemic theory. Hence, proteomic approaches can be used to shed light on further TCM research (Lao et al., 2014). Patrinia scabra Bunge (PSBE) is indigenous to northeastern China and exhibits sedative, analgesic, anti-bacterial, and anti-tumor activities (Gu et al., 2002). PSBE is often used in traditional medicine to treat intestinal carbuncles, dysentery, and cervical and gastric cancers. Modern pharmacological studies show that plants of Patrinia have significant anti-tumor effects (Yang et al., 2011). Our previous study isolated lariciresinol (LA) from PSBE lignans and reported its potent anti-cancer effects on HepG2 cells (Ma et al., 2016), and the molecular pathway of cell apoptosis might be concerned with the ubiquitin-proteasome pathway, but the specific molecular mechanisms of LA-induced apoptosis are largely elusive. Apoptosis is programmed cell death and an important self-regulatory mechanism for multicellular organisms to maintain homeostasis. Apoptosis is a key cell survival process when it inhibits only tumor cells (Lin et al., 2016). Thereby, promoting apoptosis has become the focus of anti-cancer research. There are two main pathways assosiated with apoptosis: a pathway mediated by cell death receptor and a pathway mediated by mitochondrion, both of which lead to activate of caspases cascade (Shrivastava et al., 2015). The mitochondrial-mediated apoptosis pathway is mainly managed through the deliver of cytochrome c and activation of caspase-9; Of which, mitochondria plays a vital role in this apoptosis pathway. In addition, Bcl-2 family members are very important players that regulate the release cytochrome c into the cytosol. Then cytochrome c activates the initiator caspase-9 to generate the apoptosome, subsequently leading to activate caspase-3, eventually resulting in cell apoptosis (Frión-Herrera et al., 2015). Many studies have demonstrated that natural active molecules, including from Scutellaria barbata (Yang et al., 2014), as well as tubeimoside-1 (Jia et al., 2015), ursolic acid (Weng et al., 2014, Weng et al., 2014), and swainsonine (Huang et al., 2014) extracted from TCMs, induce cancer cell apoptosis via a mitochondrial-dependent pathway. Mitochondria are likely the primary target for TCM compounds, as the mitochondrial-dependent apoptosis pathway is important for TCMs to induce cancer cells apoptosis.