Abstract
Liver cancer is a global disease with a high mortality rate and limited treatment options. Alternations in apoptosis of tumor cells and immune cells have become an important method for detailing the underlying mechanisms of hepatocellular carcinoma (HCC). Bcl-2 family, Caspase family, Fas and other apoptosis-related proteins have also become antagonistic targets of HCC. Da Huang (Rhei Radix et Rhizoma, RR), a traditional Chinese herb, has recently demonstrated antitumor behaviors. Multiple active metabolites of RR, including emodin, rhein, physcion, aloe-emodin, gallic acid, and resveratrol, can successfully induce apoptosis and inhibit HCC. However, the underlying mechanisms of these metabolites inhibiting the occurrence and development of HCC by inducing apoptosis is complicated owing to the multi-target and multi-pathway characteristics of traditional Chinese herbs. Accordingly, this article reviews the pathways of apoptosis, the relationship between HCC and apoptosis, the role and mechanism of apoptosis induced by mitochondrial endoplasmic reticulum pathway and death receptor pathway in HCC and the mechanism of six RR metabolites inhibiting HCC by inducing apoptosis.
Highlights
Liver cancer is one of the five most common malignancies worldwide and comprises the second leading cause of cancer-related deaths, with an increasing incidence rate (Marengo et al, 2016)
These pathways are regulated by mitochondrial outer membrane permeabilization (MOMP), which can be changed by permeability transition pore complexes (PTPC) and the B-cell lymphoma-2 (Bcl-2) protein family members with pore-forming activity (Green and Kroemer 2004; Vande Walle et al, 2007)
Death receptors associated with Hepatocellular carcinoma (HCC) apoptosis include Fas, Death receptor 5 (DR5), Death receptor 4 (DR4), death receptor 3 (DR3) and Tumor necrosis factor receptor 1 (TNFR1), which exist on the cell surface in the form of membrane molecules and bind with TNF-related apoptosisinducing ligand (TRAIL) to induce apoptosis
Summary
Liver cancer is one of the five most common malignancies worldwide and comprises the second leading cause of cancer-related deaths, with an increasing incidence rate (Marengo et al, 2016). Hepatocellular carcinoma (HCC) accounts for 80–85% of liver cancer cases, and its frequency of occurrence varies greatly from region to region. HCC patients face extremely low survival rates and limited treatment options with high costs (Gravitz 2014; Orcutt and Anaya 2018). The role of insufficient apoptosis in the development and progression of some cells, including hepatocytes, has become the primary focus in detailing the underlying mechanism and potential treatment targets of HCC. As a natural barrier inhibiting the development of cancer, apoptosis is a programmed cell death mechanism that is finely regulated at the genetic level, leading to the effective elimination of damaged
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