Altered Cell to Cell Communication, Autophagy and Mitochondrial Dysfunction in a Model of Hepatocellular Carcinoma: Potential Protective Effects of Curcumin and Stem Cell Therapy

Tork, Ola M.; Khaleel, Eman F.; Abdelmaqsoud, Omnia M

doi:10.7314/apjcp.2015.16.18.8271

Cited by 23 publications

(16 citation statements)

References 47 publications

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“…Furthermore, they release, among other proinflammatory cytokines, TNF-α which is one of the early events in many types of liver damage and can activate HSCs and modulate innate immune and inflammatory responses ( Gupta et al, 2019 ). In the present study, liver content of both TGF-1β and TNF-α were significantly increased upon administration of DEN+CCl4, the results that are in accordance with that reported by Tork et al (2016) , Elguindy et al (2016) and Knight et al (2017) .…”

Section: Discussionsupporting

confidence: 93%

Antisense Tissue Factor Oligodeoxynucleotides Protected Diethyl Nitrosamine/Carbon Tetrachloride-Induced Liver Fibrosis Through Toll Like Receptor4-Tissue Factor-Protease Activated Receptor1 Pathway

et al. 2021

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Tissue factor (TF) is a blood coagulation factor that has several roles in many non-coagulant pathways involved in different pathological conditions such as angiogenesis, inflammation and fibrogenesis. Coagulation and inflammation are crosslinked with liver fibrosis where protease-activated receptor1 (PAR1) and toll-like receptor4 (TLR4) play a key role. Antisense oligodeoxynucleotides are strong modulators of gene expression. In the present study, antisense TF oligodeoxynucleotides (TFAS) was evaluated in treating liver fibrosis via suppression of TF gene expression. Liver fibrosis was induced in rats by a single administration of N-diethyl nitrosamine (DEN, 200 mg/kg; i. p.) followed by carbon tetrachloride (CCl4, 3 ml/kg; s. c.) once weekly for 6 weeks. Following fibrosis induction, liver TF expression was significantly upregulated along with liver enzymes activities and liver histopathological deterioration. Alpha smooth muscle actin (α-SMA) and transforming growth factor-1beta (TGF-1β) expression, tumor necrosis factor-alpha (TNF-α) and hydroxyproline content and collagen deposition were significantly elevated in the liver. Blocking of TF expression by TFAS injection (2.8 mg/kg; s. c.) once weekly for 6 weeks significantly restored liver enzymes activities and improved histopathological features along with decreasing the elevated α-SMA, TGF-1β, TNF-α, hydroxyproline and collagen. Moreover, TFAS decreased the expression of both PAR1 and TLR4 that were induced by liver fibrosis. In conclusion, we reported that blockage of TF expression by TFAS improved inflammatory and fibrotic changes associated with CCl4+DEN intoxication. In addition, we explored the potential crosslink between the TF, PAR1 and TLR4 in liver fibrogenesis. These findings offer a platform on which recovery from liver fibrosis could be mediated through targeting TF expression.

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Section: Discussionsupporting

confidence: 93%

Antisense Tissue Factor Oligodeoxynucleotides Protected Diethyl Nitrosamine/Carbon Tetrachloride-Induced Liver Fibrosis Through Toll Like Receptor4-Tissue Factor-Protease Activated Receptor1 Pathway

et al. 2021

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“…For example, curcumin treatment of prostate, colon, and lung cancer cells causes apoptosis (11)(12)(13), while causing mitotic catastrophe in pancreatic and esophageal tumor-derived cells (14,15). Furthermore, curcumin exposure was related to autophagy in melanoma and hepatocellular carcinoma cell lines (16,17).…”

Section: Introductionmentioning

confidence: 99%

Curcumin differentially affects cell cycle and cell death in acute and chronic myeloid leukemia cells

Martínez-Castillo¹,

Villegas‐Sepúlveda²,

Meraz-Ríos³

et al. 2018

Oncol Lett

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Curcumin is a phytochemical with potent anti-neoplastic properties. The antitumoral effects of curcumin in cells derived from chronic or acute myeloid leukemia have been already described. However, a comparative study of the cytostatic and cytotoxic effects of curcumin on chronic and acute myeloid leukemia cells has not yet been performed. In the present study, the cellular effects of curcumin on cell lines derived from chronic or acute myeloid leukemia were examined. Dose and time-response assays were performed with curcumin on HL-60 and K562 cells. Cell viability was evaluated with trypan blue exclusion test and cell death by flow cytometry using a fluorescent molecular probe. A cell cycle profile was analyzed, and protein markers of cell cycle progression and cell death were investigated. In the present study, the K562 cells showed a higher sensitivity to the cytostatic and cytotoxic effects of curcumin compared with HL-60. In addition, curcumin induced G1 phase arrest in HL-60 cells and G2/M phase arrest in K562 cells. Furthermore, curcumin-related cell death in HL-60 was associated with the processed forms of caspases-9 and -3 proteins, whereas in K562 cells, both the processed and the unprocessed forms were present. Accordingly, activity of these caspases was significantly higher in HL-60 cells compared with that in K562. In conclusion, curcumin elicits different cellular mechanisms in chronic or acute myeloid leukemia cells and the powerful antitumoral effect was more potent in K562 compared with HL-60 cells.

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“…This tumor is the fourth cause of cancer-associated mortality, ranking second in men and sixth in women, with >250,000 mortalities annually (1,(3)(4)(5). At present, surgical resection is the major therapeutic strategy for liver cancer, although a high rate of recurrence remains (6,7).…”

Section: Introductionmentioning

confidence: 99%

Curcumin inhibits the growth of liver cancer stem cells through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

Wang

2018

Exp Ther Med

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Abstract. Cancer stem cells are considered as a main cause of cancer recurrence. In the present study, the effects of curcumin on the growth of liver cancer stem cells (LCSCs) were investigated. The proliferation and apoptosis of LCSCs were assessed by MTT assays and flow cytometry. Changes in the expression of apoptosis-related proteins were identified by western blotting.The results of the study demonstrated that curcumin treatment inhibited the growth of LCSCs, induced cell apoptosis, as well as regulated the expression of apoptosis-associated proteins and the release of cytochrome c. Further experiments revealed that treatment with curcumin inhibited that the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Treatment with an activator of PI3K/AKT reversed the curcumin-induced growth inhibition of LCSCs. These results demonstrated that curcumin inhibited the growth of LCSCs through the PI3K/AKT/mTOR signaling pathway. Thus, the present study suggested that curcumin may be a potentially efficient agent in the treatment of liver cancer. IntroductionLiver cancer is one of the most common malignancies worldwide, with ~600,000 new cases diagnosed annually (1). However, the 5-year survival rate of liver cancer is <9% (2). This tumor is the fourth cause of cancer-associated mortality, ranking second in men and sixth in women, with >250,000 mortalities annually (1,3-5). At present, surgical resection is the major therapeutic strategy for liver cancer, although a high rate of recurrence remains (6,7).Stem cells are a type of cells harboring the ability to self-renew and differentiate (8). Cancer stem cells are a subset of cancer cells with stem cell properties. Although radiotherapy and chemotherapy can eliminate the majority of tumor cells, cancer stem cells have the ability to self-renew and differentiate to generate tumor cell heterogeneity, and thus resist these therapies (9). Liver cancer stem cells (LCSCs) are considered to account for the chemotherapy resistance and recurrence of liver cancer (10,11). Multiple signals pathways, including Notch and Wnt/β-catenin, are found to serve important roles in the stemness of LCSCs (12). The regulation of LCSCs via the manipulation of internal signaling pathways may become a feasible treatment for patients with liver cancer.Curcumin is a yellow natural compound derived from Rhizoma curcumae longae and is widely used as a spice in Asia. Curcumin has been demonstrated to exert anti-inflammatory, antioxidant and antiangiogenic effects (13-15), while it also exerts a potential antitumor effect (15-17). However, the effects of curcumin on LCSCs remain unclear. Therefore, the aim of the present study was to examine the effects of curcumin on the growth of LCSCs, as well as the underlying mechanism of its action. The study demonstrated that treatment with curcumin is able to inhibit the growth of LCSCs, and this compound may be a promising treatment agent for liver cancer. Materials and methodsC...

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Altered Cell to Cell Communication, Autophagy and Mitochondrial Dysfunction in a Model of Hepatocellular Carcinoma: Potential Protective Effects of Curcumin and Stem Cell Therapy

Cited by 23 publications

References 47 publications

Antisense Tissue Factor Oligodeoxynucleotides Protected Diethyl Nitrosamine/Carbon Tetrachloride-Induced Liver Fibrosis Through Toll Like Receptor4-Tissue Factor-Protease Activated Receptor1 Pathway

Antisense Tissue Factor Oligodeoxynucleotides Protected Diethyl Nitrosamine/Carbon Tetrachloride-Induced Liver Fibrosis Through Toll Like Receptor4-Tissue Factor-Protease Activated Receptor1 Pathway

Curcumin differentially affects cell cycle and cell death in acute and chronic myeloid leukemia cells

Curcumin inhibits the growth of liver cancer stem cells through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

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