Hepatoprotective effect of hesperidin in hepatocellular carcinoma: Involvement of Wnt signaling pathways

Zaghloul, Randa A.; Elsherbiny, Nehal M.; Kenawy, Hany I.; El-Karef, Amr; Eissa, Laila A.; El‐Shishtawy, Mamdouh M.

doi:10.1016/j.lfs.2017.07.026

Cited by 43 publications

(25 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, hesperidin protected against DEN‐induced elevation of serum AFP level and it alleviated the histomorphological features of HCC such as mitotic figures, pseudolobular formation as well as stromal and vascular invasion. Altogether, our results are consistent with the previous studies that proved the anticancer activity of hesperidin …”

Section: Discussionsupporting

confidence: 93%

“…These results were confirmed by the histopathological examination in which fatty and degenerative changes in liver tissues with necrotic hepatocytes death were observed in DEN rats. Our results are consistent with other previous studies and can be explained as DEN is a genotoxic hepatocarcinogen and its bioactivation in the liver is accompanied with increased ROS formation . Interestingly, we found that hesperidin (200 kg b.wt.)…”

Section: Discussionsupporting

confidence: 93%

“…Additionally, hesperidin targeted the same pathway to inhibit the survival of other cancer types, particularly the lung carcinoma cells . Interestingly, hesperidin was effective in targeting other pathways to protect against HCC formation such as wingless/int‐1 signaling pathway that is responsible for HCC cell proliferation and angiogenesis in addition to Nrf2/ARE/HO‐1, PPARγ, and TGF‐β1/Smad3 signaling, which are responsible for oxidative stress and inflammation . Hence, our findings confirm that downregulation of the PI3K/Akt pathway by hesperidin is one of its mechanisms by which it could protect against HCC development.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of PI3K/Akt pathway in the protective effect of hesperidin against a chemically induced liver cancer in rats

Mo’men

Hussein

Kandeil

2019

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Hesperidin is a flavanone glycoside that is found in the Citrus species and showed antioxidant, hepatoprotective as well as anticancer activity. This study investigated the effect of hesperidin on the PI3K/Akt pathway as a possible mechanism for its protective effect against diethylnitrosamine (DEN)‐induced hepatocellular carcinoma (HCC). Adult Wistar rats were divided into Control group (received drug vehicle); DEN group (received 100 mg/L of DEN solution for 8 weeks), and hesperidin + DEN group (received 200 mg/kg body weight of hesperidin/day orally for 16 weeks + DEN solution as DEN group). Our findings showed that the administration of hesperidin significantly decreased the elevation in liver function enzymes, serum AFP level, and oxidative stress markers. Moreover, hesperidin administration suppressed DEN‐induced upregulation of PI3K, Akt, CDK‐2 protein expression, and preserved the integrity of the liver tissues from HCC formation. In conclusion, the hepatoprotective activity of hesperidin is mediated via its antioxidation and downregulation of the PI3K/Akt pathway.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Involvement of PI3K/Akt pathway in the protective effect of hesperidin against a chemically induced liver cancer in rats

Mo’men

Hussein

Kandeil

2019

J Biochem & Molecular Tox

View full text Add to dashboard Cite

show abstract

“…The hepatic tumour marker, AFP, was determined in the sera samples quantitatively according to the manufacturer's procedures. 76 Briefly, samples were added to the wells of a plate coated with AFP antibodies and incubated for 1 hour. HRP-conjugate was then added to bind to the bound AFP and finally the plate was washed thoroughly.…”

Section: Serum α-Fetoprotein (Afp) Levelmentioning

confidence: 99%

A novel chemoprotective effect of tiopronin against diethylnitrosamine‐induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK‐P53 signalling cascade

Mo’men

Hussein

Kandeil

2019

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related death worldwide. Oxidative stress contributes significantly to HCC pathogenesis. In this study, we investigated the possible chemoprotective effect of the thiol group‐containing compound, tiopronin, against HCC induced chemically by diethylnitrosamine (DENA) in rats. In addition, we elucidated the possible underlying molecular mechanism. Adult male Wistar rats were divided into: Control group, DENA‐treated group and tiopronin + DENA‐treated group. Liver function tests (ALT, AST, ALP, albumin, total and direct bilirubin) as well as alpha fetoprotein (AFP) concentration were measured in the sera of samples. Oxidative stress biomarkers such as malondialdehyde, nitric oxide, catalase and glutathione peroxidase were measured in the liver tissue homogenates. Determination of the phosphorylated apoptosis signal‐regulating kinase 1 (phospho‐ASK1), phospho‐P38 and phospho‐P53 proteins by western blotting, caspase 3 by immunofluorescence in addition to histopathological examination of the liver tissues were performed. Our results showed that tiopronin prevented the DENA‐induced elevation of the liver function enzymes and AFP. It also preserved the activities of antioxidant enzymes as well as providing protection from the appearance of HCC histopathological features. Interestingly, tiopronin significantly decreased the expression level of phospho‐ASK1, phospho‐P38 and phospho‐P53, caspase 3 in the liver tissues. These novel findings suggested that tiopronin is an antioxidant drug with a chemoprotective effect against DENA‐induced HCC through maintaining the normal activity of ASK1/ P38 MAPK/ P53 signalling pathway.

show abstract

“…The recent interest in the use of flavonoids as anti-cancer agents has highlighted the effects of hesperidin in prevention and treatment of various human diseases [13][14][15]. Among the many beneficial effects on health, it has been reported that hesperidin is able to inhibit skin tumorigenesis [16].…”

Section: Introductionmentioning

confidence: 99%

Novel Lipidized Derivatives of the Bioflavonoid Hesperidin: Dermatological, Cosmetic and Chemopreventive Applications

et al. 2018

View full text Add to dashboard Cite

Hesperidin is one of the most important natural flavonoids, known for its antioxidant, anti-inflammatory, anti-mutagenic, and anti-hypertensive properties. Despite its various biological activities, hesperidin is rarely used in the dermo-cosmetic field because of its poor solubility in both water and oil phases that makes difficult formulation, distribution and bioavailability through the skin layers. Moreover, hesperidin is still underestimated in skin care products, and literature data on its stability into a topical formulation are not yet available. In this paper we report the synthesis of five different derivatives of hesperidin and their evaluation in terms of antioxidant, antifungal, antiproliferative, and apoptotic effects on human leukemic K562 cells. Preliminary antiproliferative effects were considered since hyper-proliferation is involved in several cutaneous problems particularly in the case of photo-exposition and environmental pollution. Esp4 and Esp5 were found to be more active in inhibiting K562 cell growth than parent hesperidin. Esp3 exhibited different biological properties, i.e., antioxidant activity in the absence of antiproliferative effects.

show abstract

Hepatoprotective effect of hesperidin in hepatocellular carcinoma: Involvement of Wnt signaling pathways

Cited by 43 publications

References 53 publications

Involvement of PI3K/Akt pathway in the protective effect of hesperidin against a chemically induced liver cancer in rats

Involvement of PI3K/Akt pathway in the protective effect of hesperidin against a chemically induced liver cancer in rats

A novel chemoprotective effect of tiopronin against diethylnitrosamine‐induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK‐P53 signalling cascade

Novel Lipidized Derivatives of the Bioflavonoid Hesperidin: Dermatological, Cosmetic and Chemopreventive Applications

Contact Info

Product

Resources

About