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production of nitrosamines. The enzymatic metabolism of these nitrosamines converts them from biologically inert compounds to biologically active ones. These potent hepatocarcinogens primarily metabolized in hepatocytes when acted upon by CYP2AE enzyme present in endoplasmic reticulum (ER) generate several free radicals. In addition to possible direct damage to cellular macromolecules, free radicals can also affect protein folding that may lead to protein aggregation, degradation by endoplasmic reticulum and induction of unfolded protein response. Since ER-induced refolding of proteins is a highly energy dependent process, protein misfolding will stimulate mitochondrial oxidative phosphorylation to increase ATP synthesis and reactive oxygen species (ROS). Increased ROS production leads to increased burden on mitochondria rendering it prone to oxidative injury and dysfunction.
As you know friends, mitochondria, the cellular power house involved in release of energy from food through cellular respiration naturally produces free radicals as a by-product, which are highly reactive and cause damage to cell components, such as protein and nucleic acids. But the special antioxidant defence system of mitochondria protects them from free radicals produced during cellular respiration.
However, excessively
produced ROS and free
radicals from chemical carcinogens, as mentioned above, along with inadequate scavenging of antioxidant defence system have led to cellular oxidative stress in me causing molecular events that initiated and promoted carcinogenesis. Carcinogenesis
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initiated with irreversible changes in DNA and caused mutation of DNA bases. It further led to development and progression of disease by activating the mechanisms of perpetual inflammation, cell proliferation, migration, degradation and impaired cell death hence causing hepatocarcinogenesis. As you know HCC is one of the deadliest forms of cancer and several studies suggest that only early detection and effective treatment can increase the survival possibility of a patient. Treatment option for HCC mainly depends on factors, which include extent of liver injury, tumour size and tumour staging. High-grade tumours have poor prognosis and low-grade tumours cannot be identified for many years. Moreover, complications may arise with multifocal and advanced disease where treatment options are not available and only palliative care can be provided. Also, studies on general antioxidants in various liver cancers did not
show the expected efficacy. This could be due to the inability of these antioxidants to reach to the sub-cellular targets. Hence, OS slaughtered me by converting me into Hepatocellular carcinoma.
Friends, unfortunately, I was not able to prevent oxidative stress and HCC, but there is good news for your buddies. A group of researchers from Manipal (MAHE), Karnataka, Sachin Shetty and Anushree Salian, under the guidance of Dr Sanjay Bharati and Dr Rajesh Kumar found a novel strategy to
combat HCC using a mitochondrial targeted antioxidant mito-TEMPO. Sachin says these antioxidants can effectively protect against oxidative stress since they are particularly engineered for mitochondrial accumulation. Mito-TEMPO acts in a similar manner to
Liver cancer is one of the major causes of cancer- related mortality and is the fifth most deadly cancer. Among the liver cancers, the one I was diagnosed with was hepatocellular carcinoma (HCC), which is a major sub-type and accounts for about 75% of total liver cancers.