Synergistic effect of curcumin and piperine in suppression of DENA-induced hepatocellular carcinoma in rats

Patial, Vikram; Mahesh, S. S.; Sharma, Supriya; Pratap, Kunal; Singh, Damanpreet; Padwad, Yogendra

doi:10.1016/j.etap.2015.07.012

Cited by 60 publications

(47 citation statements)

References 36 publications

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“…Histopathological study showed characteristic lesions of HCC, including anaplastic hepatocytes, multilobular biliary cysts (BC), fatty change (FC) and trabecular pattern (Figure ). Patial et al . reported that HCC could be induced in rats supplied with 0.01% solution of DENA for 10 weeks.…”

Section: Discussionmentioning

confidence: 99%

Zinc oxide nanoparticles as a novel anticancer approach; in vitro and in vivo evidence

Hassan

Mansour

Abo-Youssef

et al. 2017

Clin Exp Pharma Physio

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Currently, the outcomes of conventional chemotherapeutic approaches are unsatisfactory. Clinical application of nanoparticles seems promising. We aim to evaluate the possible antitumor activity of zinc oxide nanoparticles (ZnONPs) as a chemotherapeutic approach in in vitro and in vivo experimental models. An in vitro study was performed on three different cell lines, namely human hepatocellular carcinoma (HEPG2), human prostate cancer (PC3), and none-small cell lung cancer (A549) cell lines. An in vivo study using diethylnitrosamine (DENA)-induced HCC in adult male Wistar rats was conducted to investigate the potential antitumor activity of ZnONPs in HCC and the possible underlying mechanisms. Hepatocellular carcinoma (HCC) was induced by oral administration of DENA given in drinking water (100 mg/L) for 8 weeks. Rats were allocated into four groups, namely a control group, an HCC control group receiving DENA alone, a ZnONPs (10 μg/kg per week, intravenous (i.v.) for 1 month) control group, and a ZnONPs treatment group (receiving ZnONPs + DENA). ZnONPs significantly reduced the elevated serum levels of HCC-related tumor markers alphafetoprotein and alpha-l-fucosidase and the apoptotic marker caspase-3 compared with the untreated HCC rats. In addition, treatment with ZnONPs significantly decreased the elevated levels of hepatocyte integrity and oxidative stress markers as compared with the untreated HCC control group. Furthermore, the histopathological study revealed anaplasia and fibrous degenerations which were significantly corrected by ZnONPs treatment. In conclusion, administration of ZnONPs exhibited a promising preclinical anticancer efficacy in HCC and could be considered as a novel strategy for the treatment HCC in clinical practices.

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Section: Discussionmentioning

confidence: 99%

Zinc oxide nanoparticles as a novel anticancer approach; in vitro and in vivo evidence

Hassan

Mansour

Abo-Youssef

et al. 2017

Clin Exp Pharma Physio

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“…Behaving synergistically, the second agent enhances the curcumin's anti-cancer activity. Doxorubicin (Zhao et al, 2015;Lv et al, 2016;Dash and Konkimalla, 2017a); docetaxel (Bayet-Robert et al, 2010;Yan et al, 2016); gemcitabine (Dhillon et al, 2008;Epelbaum et al, 2010;Kanai et al, 2011), celebrex (Lev-Ari et al, 2005;Abdallah et al, 2018), paclitaxel (Ganta and Amiji, 2009;Boztas et al, 2013;Abouzeid et al, 2014;Sarisozen et al, 2014;Kim et al, 2016;Yang et al, 2017;Calaf et al, 2018), campthotecin (Xiao et al, 2015), cisplatin (Li et al, 2017), resveratrol (Du et al, 2013), epigallocatechin gallate (EGCG) (Vivar-Quintana et al, 2006;Jin et al, 2017), sulforaphane (Danafar et al, 2018) and piperine (Shaikh et al, 2009;Kakarala et al, 2010;Patial et al, 2015;Vecchione et al, 2016;Tang et al, 2017;Baspinar et al, 2018) are among the active molecules studied in combination with curcumin for their synergistic anticancer behavior.…”

Section: Introductionmentioning

confidence: 99%

Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model

Bolat

İşlek

Demir

et al. 2020

Front. Bioeng. Biotechnol.

123

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Combination chemotherapy, administrating two chemotherapeutic agents concurrently, comes into prominence, as the heterogeneity or the level of the disease necessitates a collaborative action. Curcumin, isolated from turmeric, and piperine, isolated from black long pepper, are two dietary polyphenols studied for their intrinsic anti-cancer properties against various cancer types including colorectal cancer (CRC). Furthermore, piperine improves the therapeutic effect of curcumin. Addressing this mutual behavior, this study combines curcumin and piperine within emulsome nanoformulations. Curcumin-(CurcuEmulsomes) and piperine-loaded emulsomes (PiperineEmulsomes) have established a uniform, stable, spherical dispersion with average diameters of 184.21 and 248.76 nm, respectively. The solid tripalmitin inner core achieved encapsulation capacities of up to 0.10 mg/ml curcumin and 0.09 mg/ml piperine content. While piperine treatment alone-in its both free and emulsome forms-showed no inhibition in the proliferation of HCT116 cells in vitro, its presence as the second drug agent enhanced curcumin's effect. Combination of 7 µM PiperineEmulsome and 25 µM CurcuEmulsome concentrations was found to be most effective with an inhibition of cell proliferation of about 50% viability. Cell cycle arrest at G2/M phase and induced apoptosis verified the improved anti-cancer characteristics of the therapy. While CurcuEmulsomes achieved a fourfold increase in Caspase 3 level, combination of treatment with PiperineEulsomes achieved a sixfold increase in the level of this apoptotic marker. Combinational treatment of HCT116 cells with CurcuEmulsomes and PiperineEmulsomes improved the anticancer activity of the compounds and highlighted the potential of the approach for further in vivo studies.

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“…In our study, HCC was induced chemically in rats by the well‐established DENA model . In this model, administration of DENA to Wistar rats in the drinking water for 8 weeks was reported as a complete hepatocarcinogen for HCC induction in which DENA can function as both tumour initiator and promoter simultaneously .…”

Section: Discussionmentioning

confidence: 90%

“…In our study, HCC was induced chemically in rats by the well-established DENA model. 28,29 In this model, administration of DENA to Wistar rats in the drinking water for 8 weeks was reported as a complete hepatocarcinogen for HCC induction in which DENA can function as both tumour initiator and promoter simultaneously. 13,30 We employed this particular model due to its ease of applicability over the other routes of administration such as oral gavage 31 or intraperitoneal injection of DENA 32,33 in which the latter may additionally produce a drug-drug interaction with the intraperitoneally injected tiopronin or combining DENA with other drugs as sodium phenobarbital or thioacetamide.…”

Section: Discussionmentioning

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

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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.

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Synergistic effect of curcumin and piperine in suppression of DENA-induced hepatocellular carcinoma in rats

Cited by 60 publications

References 36 publications

Zinc oxide nanoparticles as a novel anticancer approach; in vitro and in vivo evidence

Zinc oxide nanoparticles as a novel anticancer approach; in vitro and in vivo evidence

Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model

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

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