Tanshinone IIA and hepatocellular carcinoma: A potential therapeutic drug

Abstract

Because of its high prevalence and poor long-term clinical treatment effect, liver disease is regarded as a major public health problem around the world. Among them, viral hepatitis, fatty liver, cirrhosis, non-alcoholic fatty liver disease (NAFLD), and autoimmune liver disease are common causes and inducements of liver injury, and play an important role in the occurrence and development of hepatocellular carcinoma (HCC). Tanshinone IIA (TsIIA) is a fat soluble polyphenol of Salvia miltiorrhiza that is extracted from Salvia miltiorrhiza. Because of its strong biological activity (anti-inflammatory, antioxidant), it is widely used in Asia to treat cardiovascular and liver diseases. In addition, TsIIA has shown significant anti-HCC activity in previous studies. It not only has significant anti proliferation and pro apoptotic properties. It can also play an anti-cancer role by mediating a variety of signal pathways, including phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-B (NF-κB). This review not only reviews the existing evidence and molecular mechanism of TsIIA’s anti-HCC effect but also reviews the liver-protective effect of TsIIA and its impact on liver fibrosis, NAFLD, and other risk factors for liver cancer. In addition, we also conducted network pharmacological analysis on TsIIA and HCC to further screen and explore the possible targets of TsIIA against hepatocellular carcinoma. It is expected to provide a theoretical basis for the development of anti-HCC-related drugs based on TsIIA.

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

“…One critical aspect is the excessive activation of the classical inflammatory signaling pathway NF-kB. The activation of the NF-kB pathway can lead to the secretion of proinflammatory cytokines such as tumor necrosis factorα, interleukin-1 (IL-1), and IL-6, and transforming growth factor-b, which are linked to liver ailments [ 120 ]. These molecular signaling pathways promote the development of MASLD to HCC.…”

Recent Insights into the Biomarkers, Molecular Targets and Mechanisms of Non-Alcoholic Steatohepatitis-Driven Hepatocarcinogenesis

“…It has been recently reported that natural products, including phenols, flavonoids, glycosides, quinones, terpenoids, pyrazines, alkaloids, and phenylpropanoids, have antioxidant, energy-producing, anti-inflammatory, anti-apoptotic, and anti-aging effects, which mainly influence the AMPK/Nrf2/mTOR, Nrf2/HO-1, NAMPT/NAD(+)/SIRT, AMPK/SIRT1/PGC-1alpha and PKCs/PARPs/NF-kB signaling pathways, thereby regulating NAD(+) metabolism to prevent and treat NAFLD [ 117 ]. Hepatoprotective effects, caused by the inhibition of PI3K/Akt/mTOR signaling and effective alleviation of oxidative stress damage and ER stress induced by excessive lipid accumulation in hepatocytes, and activation of autophagy were observed for agonists of AMPK thymoquinone [ 118 ] and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) [ 119 ], agonist of GLP-1/glucagon cotadutide [ 120 ], an antagonist of sphingosine 1-phosphate receptor 2 (S1PR2) JTE-013 [ 26 ], activator of PI3K, autophagy-related genes (ATG) and agonist of Nrf2, PPARα and hemeoxygenase-1 (HO-1) pterostilbene [ 121 ], flavonoid with antioxidant properties involving CYP7A1, quercetin [ 122 ], Pueraria flavonoids [ 92 ], a novel gerotherapy compound, BIOIO-1001 [ 123 ], a natural nonenzymatic antioxidant with low toxicity schisandrin B (Sch B) [ 124 ], H1-antihistamines (AHs) [ 125 ], fat soluble polyphenol Tanshinone IIA (TsIIA) [ 126 ], purendan (PRD) [ 127 ], down-regulating the expression of p-mTOR, p-S6K1 and SREBP-1c, chrysin [ 128 ], red pepper seed extract (RPS) [ 129 ], Gardenia Fructus (GF) extracts [ 130 ], curcumin [ 131 ], and magnesium [ 132 ].…”

Formulation and Evaluation on Synergetic Anti-Hepatoma Effect of a Chemically Stable and Release-Controlled Nanoself-Assembly with Natural Monomers

“…For example, TAN-induced HepG2 and Hep3B liver cancer cell apoptosis by activating the caspase-3 and Caspase-8/9 via miR30b-p53-PTPN11/SHP2 signaling pathway, prevented the proliferation of the HepG2 and SMMC-7721 HCC cell lines by downregulating the expression of MMP-2 and MMP-3/9 and blocking NF-κB activation, and inhibited cell invasion and migration by regulating the expression level of E-cadherin and vimentin in HCC cells via TGF-β signaling pathway. 10 TAN inhibited cancer cell-line proliferation by blocking the STAT3 signaling pathway. 3 It is worth noting that the above related signaling pathways have also been confirmed to be closely related to the antioxidant activity and anti-inflammatory response of TAN.…”

“…[35][36][37][38][39] For instance, TAN and GA induce cancer cell apoptosis by activating the caspase-3 and Caspase-8/9 via miR30b-p53-PTPN11/SHP2 and MEK-ERK signaling pathways, respectively. 3,10,13 And TAN and GA prevent the proliferation and migration of cancer cells by regulating the expression level of E-cadherin and vimentin in HCC cells via TGF-β and ROS/PKC-α/ERK signaling pathway, respectively. [40][41][42][43] The Results of Process Optimization…”