Hepatocellular carcinoma (HCC) is the most common form of liver cancer and BCL-2 and p53 prevents the progression of HCC by apoptosis.

Hepatocellular Carcinoma and Role of BCL-2 and p53

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. In the current scenario, HCC is the third dominating cause of mortality associated with cancer worldwide. It is predicted that more than one million individuals will be suffered from liver cancer annually, by 2025.

Causes of Hepatocellular Carcinoma

The most common type of primary liver cancer that occurs in people with chronic liver diseases is cirrhosis, which is caused by hepatitis B or hepatitis C infection. Several conditions may lead to chronic hepatitis and cirrhosis or hepatocellular carcinoma, including viral agents, alcohol abuse, and metabolic derangements.

Risk Factors of Hepatocellular Carcinoma

Common risk factors for liver cancer include heavy alcohol consumption, hepatitis B virus (HBV), hepatitis C virus, obesity, tobacco smoking, diabetes, and genetic factors. 

Fibrosis and Cirrhosis as Predispositions of HCC

Chronic liver inflammation may develop into severe liver fibrosis and cirrhosis, which were predispositions of HCC. It was reported that up to 90% of HCC cases occurred in the background of liver cirrhosis or fibrosis.

Mitochondrial Pathways of Apoptosis

Apoptosis is one such cell death pathway that allows a damaged or stressed cell to deconstruct in a regulated manner without causing inflammation and has garnered much attention in the cancer field, with hopes of eliminating malignant cells through its activation.

In mammals, activation of caspases is under the tight control of the Bcl-2 family proteins, named in reference to the first discovered mammalian cell death regulator. These proteins mainly act by regulating the release of caspases activators from mitochondria.

Mitochondria appear today as the central executioner of apoptosis. Cyt-C is one of the apoptotic factors released by mitochondria into the cytoplasm and can bind to Apaf-1 (apoptosis protease activating factor) and induce cell apoptosis. The p53 tumor suppressor protein plays a central role in the regulation of apoptosis.

Beta Cell Lymphoma-2

The Beta Cell Lymphoma-2 (BCL-2) protein family is an important metabolic regulator of apoptosis; it is expressed in some tumor cells that are recognized as a key factor in regulating apoptosis. It regulates intracellular signals (pro-apoptotic and anti-apoptotic) that mediate the mitochondrial membrane permeability. Bcl-2 protein overexpression facilitates the survival of cells.


p53 has been referred to as the “guardian of the genome”. It conserves genome stability by preventing mutations. BCl2 is an anti-apoptotic gene that inhibits the apoptosis of cancer cells.

p53 is the most important pro-apoptotic protein that plays a central role in cancer development and progression by interacting with the Bcl-2 family protein to activate the mitochondria-initiated intrinsic pathway.

p53 upregulates Bax, one of the crucial pro-apoptotic members, and downregulates Bcl-2, an antiapoptotic protein that can form heterodimers with Bax.

Bax modulates mitochondrial outer membrane permeability and the release of Cytochrome C leading to activation of the downstream apoptotic pathway. As a result, mitochondrial-initiated apoptosis can be promoted and up regulated via Bad (pro-apoptotic protein) containing only the BH3 homology region and like that of Bax with multiple homology regions.


By Najeeb Ullah khan