Curcumin ameliorate DENA-induced HCC via modulating TGF-β, AKT, and caspase-3 expression in experimental rat model

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. In laboratory animal models, diethylnitrosamine (DENA) is a well-known agent that has a potent hepatocarcinogenic effect that is used to induce HCC. As curcumin has a potent anti-inflammatory effect with strong therapeutic potential against a variety of cancers, our present study aims to investigate its curative effects and the possible mechanisms of action against DENA-induced HCC in male rats. Investigation of biochemical and molecular parameters of HCC animal model liver showed an overexpression of TGF-β and Akt proteins accompanied with a significant reduction of the proapoptotic marker caspase-3. DENA-induced hepatic cellular injury resulted also in a significant increase in liver function marker enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid peroxides in this group. Curcumin treatment partially reversed DENA-induced damage as it reduced the overexpression of the angiogenic and anti-apoptotic factors TGF-β and Akt and improved caspase-3 expression. Also, it could partially normalize the serum values of liver marker enzymes and lipid peroxidation and improve liver architecture. Curcumin shows a unique chemotherapeutic effect in reversing DENA-induced HCC in rat model. This effect is possibly mediated through its proapoptotic, antioxidant, anti-angiogenic, as well as antimitotic effects. It interferes and modulates cell signaling pathways and hence turns death signals and apoptosis on within tumor cells.

Spices for Prevention and Treatment of Cancers

“…HIF-1α and HIF-2α protein levels were lowered by curcumin in hypoxia, and ARNT protein levels and HIF transcriptional activity were reduced in normoxia and hypoxia by curcumin, and survival of Hep3B hepatoma cells was negatively impacted [43]. Diethylnitrosamine (DENA)-induced hepatocarcinogenesis and damage were prevented and reversed by curcumin in rats [44,45]. Curcumin remarkably suppressed the serum levels of α feto-protein (AFP), interleukin-2 (IL-2), interleukine-6 (IL-6), alanine amino transferase (ALT), and malondialdehyde (MDA) as well as gene expression of IL-2 and IL-6, and increased the gene expression and activities of glutathione peroxidase (Gpx), glutathione reductase (GR), catalase (CAT) and super oxide dismutase (SOD) [44].…”

“…Moreover, the overexpression of the angiogenic and anti-apoptotic factors transforming growth factor-β (TGF-β) and protein kinase B (PKB) were reduced, while caspase-3 expression was improved. Liver marker enzymes aspartate aminotransferase (AST) and ALT and lipid peroxidation were normalized [45]. In addition, curcumin inhibited the growth of liver cancer in a dose-dependent manner in nude mice [46].…”

Experimental evidence for the therapeutic potential of tempol in the treatment of acute liver injury

“…The samples were separated electrophoretically at 100 volts for 2 h as previously described [34,35]. The separated proteins were electrically transferred onto PVDF membrane using T-77 ECL semidry transfer unit from Amersham Biosciences for 2 h. The membrane was blocked in TBS buffer containing 0.05 % Tween and 5 % non-fat milk for 1 h. The membranes were then incubated either with mouse monoclonal anti NFj-B p65, anti TNF-a, anti Bcl-2 (Santa Cruz Biotechnology, INC.), anti-active Caspase-3 (ab 32042), or anti b-actin antibodies.…”

lncRNA‐PDPK2P promotes hepatocellular carcinoma progression through the PDK1/AKT/Caspase 3 pathway

“…These results suggest that the amount of microRNA that binds to PDPK2P increases with increased PDPK2P expression, resulting in a decrease in the amount of microRNA bound to mRNA‐PDK1 and thereby increasing the amount of PDK1 involved in the AKT pathway. The increased involvement of PDK1 promotes the effects of the AKT pathway, enhancing proliferation and reducing apoptosis of HCC cells (Abouzied et al ., ). These experimental results indicate that lncRNA‐PDPK2P promotes HCC progression through the PDK1/AKT/caspase 3 signaling pathway.…”

“…Hepatocellular carcinoma (HCC) is one of the world's most common malignancies with one of the worst prognoses (Abouzied et al, 2015;Zuo et al, 2015). A large body of evidence suggests that the incidence of HCC is closely related to hepatitis B virus whose infection can lead to chronic liver injury and necrotizing inflammation (Fung et al, 2009) causing repeated liver cell proliferation, DNA repair, and eventually HCC (Guo et al, 2000).…”