In-vitro and in-vivo investigation of amygdalin, metformin, and combination of both against doxorubicin on hepatocellular carcinoma

Mamdouh, Ahmed; Khodeer, Dina M.; Tantawy, Mohamed A.; Moustafa, Yasser M.

doi:10.1016/j.lfs.2021.119961

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…This indicates that Amy has a better effect on Sor’s toxic effects when combined, which is a promising attribute in overcoming Sor’s toxic effects. These results were consistent with several previous investigations [ 67 , 68 ].…”

Section: Discussionsupporting

confidence: 94%

Hepatocellular Carcinoma cells: activity of Amygdalin and Sorafenib in Targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death

El-Sewedy,

Salama,

Mohamed

et al. 2023

BMC Complement Med Ther

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Background Sorafenib (Sor) is the only approved multikinase inhibitor indicated for the treatment of HCC. Previous studies have shown that amygdalin (Amy) possesses anticancer activities against several cancer cell lines; we suggested that these compounds might disrupt AMPK/mTOR and BCL-2. Therefore, the current study used integrated in vitro and in silico approaches to figure out Amy and Sor’s possible synergistic activity in targeting AMPK/mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death in HepG2 cells. Results Notably, Amy demonstrated exceptional cytotoxic selectivity against HepG2 cells in comparison to normal WI-38 cells (IC50 = 5.21 mg/ml; 141.25 mg/ml), respectively. In contrast, WI-38 cells were far more sensitive to the toxicity of Sor. A substantial synergistic interaction between Amy and Sor was observed (CI50 = 0.56), which was connected to cell cycle arrest at the S and G2/M stages and increased apoptosis and potential necroptosis. Amy and Sor cotreatment resulted in the highest glutathione levels and induction of pro-autophagic genes AMPK, HGMB1, ATG5, Beclin 1, and LC3, suppressed the mTOR and BCL2 anti-apoptotic gene. Finally, the docking studies proposed that Amy binds to the active site of the AMPK enzyme, thus inhibiting its activity. This inhibition of AMPK ultimately leads to inhibition of mTOR and thus induces apoptosis in the HepG2 cells. Conclusion Although more in vivo research using animal models is needed to confirm the findings, our findings contribute to the evidence supporting Amy’s potential anticancer effectiveness as an alternative therapeutic option for HCC.

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Section: Discussionsupporting

confidence: 94%

Hepatocellular Carcinoma cells: activity of Amygdalin and Sorafenib in Targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death

El-Sewedy,

Salama,

Mohamed

et al. 2023

BMC Complement Med Ther

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“…Previously, Zhou et al (2012) studied the progress inhibition and initiation of apoptosis carried by Amygdalin and/or combined with β-D-glucosidase and verified a cyto-activity on HepG-2 cells by dosedependent induction of apoptosis. The present obtained data agreed with the recent findings of Mamdouh et al, (2021) who studied the effect of different concentrations of Amygdalin and Doxorubicin in vitro and in vivo using HepG-2 and Huh-7 cell lines for 24, 48 and 72hrs, and they found a dosedependent effect on cellular proliferation.…”

Section: The Efficiency Of Amygdalin and Doxorubicin Combination On H...supporting

confidence: 93%

The efficiency of amygdalin and doxorubicin combination on hepatocellular carcinoma and stromal myofibroblastic prostatic cells

Badr

Attia

Salim

2022

African Journal of Biological Sciences

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This study investigated the possible therapeutic potential of Amygdalin either alone or in combination with Doxorubicin against HepG-2 liver cancer cells and on normal stromal myofibroblastic prostatic (WPMY-1) cells. After determination of IC50 concentrations of Amygdalin and Doxorubicin by MTT assay, each cell line was treated for 48 hrs as follows: Untreated control cells, Amygdalin-only treatment, Doxorubicin-only treatment, and a combination of Amygdalin + Doxorubicin treatment in an equal ratio (1:1). In HepG-2 cells, the treatment with Amygdalin or Doxorubicin significantly decreased the number of surviving cells in a dose-dependent manner. In normal WPMY-1 cells, the percentages of surviving cells were constant and unaffected by increasing Amygdalin or Doxorubicin concentrations, demonstrating no IC50 dose impact threshold. In HepG-2 cells, the Amygdalin and Doxorubicin 1:1 combination at their IC50 concentrations showed a synergistic effect (combination index (CI)= 0.69153). In addition, the average normalized mRNA expression of BCL-2 was downregulated and that of BAX was found overexpressed by all treatments in HepG-2 cells, most significant with the combination treatment. In WPMY-1 cells, both BCL-2 and BAX were downregulated after all treatments, in contrast to the probable behavior against cancer cells. The flow cytometry analysis showed that the combination treatment to HepG-2 cells induced a higher percentage of early and late apoptotic cells than >Doxorubicin >Amygdalin. In WPMY-1 cells, only early apoptotic cells were significantly enhanced by Doxorubicin either alone or in combination with Amygdalin, with no intergroup significant changes in apoptotic cell numbers. The study indicates that Amygdalin synergistically enhances the chemotherapeutic potential of Doxorubicin against malignant cells when used in combination through the induction of apoptosis.

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“…The generation of ROS in the case of Pb-induced toxicity occurs through one of the following mechanisms: (i) inhibition of δ-ALAD by Pb and accumulation of the substrate δ-ALA, which can be oxidized to produce ROS [ 15 , 43 ], and (ii) stimulation of ferrous ion-induced membrane lipid peroxidation due to Pb treatment [ 50 ]. Consistent with recent studies [ 51 , 52 ], the results of this study confirmed a remarkable inhibition of the antioxidant enzymes (SOD, GSH-PX, and GST) in rats after 6 weeks of Pb-acetate treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Glutathione plays a vital role in the scavenging of reactive oxygen radicals. The treatment of animals with Pb oxidized both GSH and GSSG enzymes and reduced the GSH/GSSG ratio, which acts as a good marker of oxidative stress [ 15 ]. The levels of reduced glutathione, GSH, in fish treated with Pb were decreased by the binding of Pb to SH groups in GSH, which affects the antioxidant activity of GSH [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Glycine Betaine Relieves Lead-Induced Hepatic and Renal Toxicity in Albino Rats

Abdelrazek

Salama

Alharthi

et al. 2022

Toxics

Self Cite

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Lead (Pb) is a widespread and nondegradable environmental pollutant and affects several organs through oxidative mechanisms. This study was conducted to investigate the antioxidant protective effect of glycine betaine (GB) against Pb-induced renal and hepatic injury. Male albino rats (n = 45) were divided into three groups: G1 untreated control, G2 Pb-acetate (50 mg/kg/day), and G3 Pb-acetate (50 mg/kg/day) plus GB (250 mg/kg/day) administered for 6 weeks. For G3, Pb-acetate was administered first and followed by GB at least 4 h after. Pb-acetate treatment (G2) resulted in a significant decrease in renal function, including elevated creatinine and urea levels by 17.4% and 23.7%, respectively, and nonsignificant changes in serum uric acid levels. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphates (ALP) activities were significantly increased with Pb treatment by 37.6%, 59.3%, and 55.1%, respectively. Lipid peroxidation level was significantly increased by 7.8 times after 6 weeks of Pb-acetate treatment. The level of reduced glutathione (GSH-R) significantly declined after Pb-acetate treatment. Pb-acetate treatment also reduced the activities of superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GSH-PX) by 74.1%, 85.0%, and 40.8%, respectively. Treatment of Pb-intoxicated rats with GB resulted in a significant reduction in creatinine, urea, ALT, AST, and lipid peroxidation, as well as a significant increase in the level of GSH-R and in the activities of ALP, SOD, GST, and GSH-PX. The molecular interaction between GB and GSH-PX indicated that the activation of GSH-PX in Pb-intoxicated rats was not the result of GB binding to the catalytic site of GSH-PX. The affinity of GB to bind to the catalytic site of GSH-PX is lower than that of H2O2. Thus, GB significantly mitigates Pb-induced renal and liver injury through the activation of antioxidant enzymes and the prevention of Pb-induced oxidative damage in the kidney and liver.

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In-vitro and in-vivo investigation of amygdalin, metformin, and combination of both against doxorubicin on hepatocellular carcinoma

Cited by 7 publications

References 31 publications

Hepatocellular Carcinoma cells: activity of Amygdalin and Sorafenib in Targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death

Hepatocellular Carcinoma cells: activity of Amygdalin and Sorafenib in Targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death

The efficiency of amygdalin and doxorubicin combination on hepatocellular carcinoma and stromal myofibroblastic prostatic cells

Glycine Betaine Relieves Lead-Induced Hepatic and Renal Toxicity in Albino Rats

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