quercetin and Liver-Neoplasms

Hepatitis B virus (HBV) infection is a worldwide health problem, and chronic infection can cause many diseases ranging from liver fibrosis to hepatocellular carcinoma (HCC) by complicated mechanisms. Currently, the treatment of HBV infection mainly depends on interferons (IFNs) and nucleotide analogues (NAs); however, both have some limitations. In 2012, sodium taurocholate cotransporting polypeptide (NTCP) was identified as the entry receptor of HBV. Based upon this groundbreaking discovery, a series of molecules have been gradually developed and evaluated to discover novel entry inhibitors targeting NTCP. However, only two macromolecules have been used for potential clinical applications so far. In this Perspective, we focus on summarizing the structural features that convey the biological functions of NTCP, as well as further discuss the anti-HBV activity and selectivity of inhibitors in HBV-related diseases, which should provide clues in the future for the discovery of drug candidates targeting NTCP.

Topics: Carcinoma, Hepatocellular; Hep G2 Cells; Hepatitis B; Hepatitis B virus; Hepatocytes; Humans; Interferons; Liver Neoplasms; Nucleotides; Organic Anion Transporters, Sodium-Dependent; Symporters; Virus Internalization

A series of polyamine conjugates of flavonoids with a naphthalene motif were synthesized and evaluated for their anti-hepatocellular carcinoma properties using in vitro and in vivo assays. Compound 8a displayed favorable selectivity between hepatocellular carcinoma cells and normal hepatocyte cells, and the combination of 8a with aspirin resulted in additive inhibition of in vitro tumor cell growth and migration. The 8a-aspirin combination also inhibited H22 liver tumor growth and pulmonary metastasis and improved body weight index in animal models. Preliminary mechanistic studies indicated that 8a increased the expression of apoptosis-related proteins such as p-p38, p-JNK, p53 and Bcl-2, an effect that was further amplified by aspirin. Therefore, a cocktail therapy of flavonoid-polyamine conjugates with aspirin has potential use as an antitumor therapy.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis Regulatory Proteins; Aspirin; Carcinoma, Hepatocellular; Cell Line; Flavonoids; Liver Neoplasms; Neoplasm Metastasis; Polyamines