Abstract
Hepato-carcinogenesis is multifaceted in its molecular aspects. Among the interplaying agents are altered gap junctions, the proteasome/autophagy system, and mitochondria. The present experimental study was designed to outline the roles of these players and to investigate the tumor suppressive effects of curcumin with or without mesenchymal stem cells (MSCs) in hepatocellular carcinoma (HCC). Adult female albino rats were divided into normal controls and animals with HCC induced by diethyl-nitrosamine (DENA) and CCl4. Additional groups treated after HCC induction were: Cur/HCC which received curcumin; MSCs/HCC which received MSCs; and Cur+MSCs/ HCC which received both curcumin and MSCs. For all groups there were histopathological examination and assessment of gene expression of connexin43 (Cx43), ubiquitin ligase-E3 (UCP-3), the autophagy marker LC3 and coenzyme-Q10 (Mito.Q10) mRNA by real time, reverse transcription-polymerase chain reaction, along with measurement of LC3II/LC3I ratio for estimation of autophagosome formation in the rat liver tissue. In addition, the serum levels of ALT, AST and alpha fetoprotein (AFP), together with the proinflammatory cytokines TNFα and IL-6, were determined in all groups. Histopathological examination of liver tissue from animals which received DENA-CCl4 only revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules. Administration of curcumin, MSCs; each alone or combined into rats after induction of HCC improved the histopathological picture. This was accompanied by significant reduction in α-fetoprotein together with proinflammatory cytokines and significant decrease of various liver enzymes, in addition to upregulation of Cx43, UCP-3, LC3 and Mito.Q10 mRNA. Improvement of Cx43 expression, nonapoptotic cell death and mitochondrial function can repress tumor growth in HCC. Administration of curcumin and/or MSCs have tumor suppressive effects as they can target these mechanisms. However, further research is still needed to verify their effectiveness.
Highlights
Hepatocellular carcinoma (HCC) is a malignancy with extremely threatening prospects and a five-year survival rate reported below 9% (Sherman, 2005)
As regards the tumor marker, serum alpha fetoprotein (AFP), it showed marked increase in the hepatocellular carcinoma (HCC) group compared to the normal control group
The levels of AFP were significantly reduced in all treated groups (p < 0.001 for all) compared with HCC group
Summary
Hepatocellular carcinoma (HCC) is a malignancy with extremely threatening prospects and a five-year survival rate reported below 9% (Sherman, 2005). Chronic liver diseases are risk factors that may predispose to HCC, as well as any factor that chronically and slowly damages the hepatocytes. This possibly happens via inducing mitosis and making the DNA of these cells more susceptible to genetic alterations (Cervello & Montalto, 2006). GJIC mainly involves three kinds of Cx-Cx26, Cx32, and Cx43-whose distribution depends on cell type and location in the liver lobule (Kojima et al, 1997). There are 2 major intracellular pathways of protein degradation: the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system (autophagy). Asian Pacific Journal of Cancer Prevention, Vol 16, 2015 8271 of 2 steps: ubiquitination and proteasome-mediated ; Khan& Mukhtar, 2015).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
