Pentoxifylline induces apoptosis of HepG2 cells by reducing reactive oxygen species production and activating the MAPK signaling

Wang, Yan; Liu, Dong; Li, Jing; Luo, Miaosha; Shang, Boxin

doi:10.1016/j.lfs.2017.05.029

Cited by 16 publications

(9 citation statements)

References 50 publications

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“…PTX also down-regulated FAS-mediated apoptosis-related proteins, FASL, FAS, FADD, PARP, and caspase 8 were down-regulated by PTX treatment. PTX inhibited the extrinsic apoptotic pathway, which is in contrast to a previous study [48]. In this in vitro study, it was found that PTX suppressed the proliferation of RAW 264.7 cells and also suppressed the expression of proteins related to cellular apoptosis.…”

Section: Discussioncontrasting

confidence: 95%

Immunomodulatory Effects of Pentoxifylline: Profiling Data Based on RAW 264.7 Cellular Signaling

Seo

Nguyen

et al. 2021

Applied Sciences

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Pentoxifylline (PTX) is a methylxanthine derivative that has been developed as an immunomodulatory agent and an improvement of microcirculation. Osteoradionecrosis (ORN) is a serious complication of radiation therapy due to hypovascularity. Coronavirus disease 2019 (COVID-19) has spread globally. Symptoms for this disease include self-limiting respiratory tract illness to severe pneumonia and acute respiratory distress. In this study, the effects of PTX on RAW 264.7 cells were investigated to reveal the possibility of PTX as a therapeutic agent for ORN and COVID-19. To reveal PTX effects at the cellular level, protein expression profiles were analyzed in the PTX-treated RAW 264.7 cells by using immunoprecipitation high-performance liquid chromatography (IP-HPLC). PTX-treated RAW 264.7 cells showed increases in immunity- and osteogenesis-related proteins and concurrent decreases in proliferation-, matrix inflammation-, and cellular apoptosis-related proteins expressions. The IP-HPLC results indicate that PTX plays immunomodulatory roles in RAW 264.7 cells by regulating anti-inflammation-, proliferation-, immunity-, apoptosis-, and osteogenesis-related proteins. These results suggest that PTX may be used as supplement medications for ORN as well as for COVID-19.

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Section: Discussioncontrasting

confidence: 95%

Immunomodulatory Effects of Pentoxifylline: Profiling Data Based on RAW 264.7 Cellular Signaling

Seo

Nguyen

et al. 2021

Applied Sciences

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“…Various studies have reported the antitumor effects of PTXF, particularly in reducing metastasis and enhancing the effects of chemotherapy and radiation [ 11 , 19 , 21 , 22 , 24 ]. For example, Wang et al injected 50, 100, and 200 mg/kg of PTXF intraperitoneally into different groups of xenograft mice with established human hepatocellular carcinoma for 28 days and found that tumor growth was significantly reduced up to 60% in all treatment groups compared to the control group, regardless of the PTXF dose [ 25 ]. Therefore, it may be postulated that continuous treatment with PTXF is more crucial than the dose, which requires further investigation in future studies.…”

Section: Discussionmentioning

confidence: 99%

Pentoxifylline changes the balance of immune cell population in breast tumor-infiltrating lymphocytes

et al. 2023

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Immunotherapy utilizing tumor-infiltrating lymphocytes (TILs) is a promising approach for cancer treatment. Pentoxifylline (PTXF), a xanthine derivative, exhibits antitumor properties. This study aimed to investigate the impact of PTXF on the phenotype and function of TILs and splenocytes in a triple-negative breast cancer (TNBC) mouse model. TNBC was subcutaneously induced in BALB/c mice, followed by nine intraperitoneal injections of 100 mg/kg PTXF. TILs were then isolated by enzymatic digestion of tumors and cocultured with 4T1 cells. The proportion of regulatory T cells (Tregs) and cytotoxic T cells in TILs and splenocytes was assessed using flow cytometry. Transforming growth factor (TGF)-β and interferon (IFN)-γ production in TILs and splenocytes cultures was measured by ELISA. Relative expression of t-bet, foxp3, gata-3, and ror-γt in TILs and splenocytes was evaluated using real-time PCR. Tumor growth in PTXF-treated mice was significantly lower than that in the controls (P < 0.01). The frequency of regulatory and cytotoxic TILs in PTXF-treated mice was approximately half (P < 0.01) and twice (P < 0.05) that of the control group, respectively. The level of TGF-β and IFN-γ in the supernatant of PTXF-treated TILs was decreased and increased, respectively (P < 0.05). The relative expression of t-bet and foxp3 in the PTXF-treated mice compared to controls was increased and decreased, respectively (P < 0.05). Changes in the immune cell balance were less significant in the spleen compared to the TILs. PTXF treatment could limit the tumor growth and modify the regulatory-to-cytotoxic TILs ratio, as well as cytokine balance of TILs, in favor of antitumor responses.

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“…High levels of ROS trigger tumor cell apoptosis (Dasgupta et al., 2019). Apoptosis is a process regulated by a series of enzymes and genes under physiological or pathological conditions (Wang et al., 2017). It is characterized by specific morphological changes, such as a condensation of chromatin, a loss of microvilli, blebbing formation, and the appearance of apoptotic bodies (Wang et al., 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis can be activated by signaling of mitogen‐activated protein kinases (MAPK; Wang et al., 2017). MAPKs contain extracellular signal‐related kinases (ERKs), stress‐activated p38 kinases, and c‐jun NH2‐terminal kinases (JNKs; Li, Li, et al., 2017; Li, Lin, et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

Intracellular ethanol‐mediated oxidation and apoptosis in HepG2/CYP2E1 cells impaired by two active peptides from seahorse (Hippocampus kuda bleeler) protein hydrolysates via the Nrf2/HO‐1 and akt pathways

Qian

Chen

Chen³

et al. 2021

Food Science & Nutrition

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Seahorse (Hippocampus kuda Bleeler) are representative marine species in aquaculture, with special value of medicine and food. In this study, the protective effects of two peptides from seahorse hydrolysates (SHP‐1 and SHP‐2) against ethanol‐mediated oxidative stress in HepG2/CYP2E1 cells were investigated. Firstly, SHP‐1 and SHP‐2 presented no cytotoxicity. Compared with the ethanol‐treated groups, SHP‐1 and SHP‐2 increased cell viability in a concentration‐dependent manner. Secondly, SHP‐1 and SHP‐2 markedly reduced intracellular reactive oxygen species (ROS) generation, gamma‐glutamyltranspeptidase (GGT) activity, and tumor necrosis factor‐α (TNF‐α) levels and remarkably enhanced superoxide dismutase (SOD) and glutathione (GSH) activities. SHP‐1 and SHP‐2 also down‐regulated the expressions of GGT, bax, c‐caspase‐8/‐9/‐3, p‐Akt, p‐IκB‐α, p‐p65, p‐ERK, and p‐p38 but up‐regulated SOD, GSH, NF‐E2‐related factor 2 (Nrf2), heme oxygenase‐1 (HO‐1), and bcl‐2 levels, as revealed by Western blot analysis. Moreover, SHP‐1 and SHP‐2 increased the mitochondrial membrane potential (MMP), reduced DNA damage, and suppressed the nuclear translocation of p65. These results suggest that two peptides from seahorse hydrolysates can be considered a potential functional biomaterial and further improve the use value of seahorse in aquaculture.

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Pentoxifylline induces apoptosis of HepG2 cells by reducing reactive oxygen species production and activating the MAPK signaling

Cited by 16 publications

References 50 publications

Immunomodulatory Effects of Pentoxifylline: Profiling Data Based on RAW 264.7 Cellular Signaling

Immunomodulatory Effects of Pentoxifylline: Profiling Data Based on RAW 264.7 Cellular Signaling

Pentoxifylline changes the balance of immune cell population in breast tumor-infiltrating lymphocytes

Intracellular ethanol‐mediated oxidation and apoptosis in HepG2/CYP2E1 cells impaired by two active peptides from seahorse (Hippocampus kuda bleeler) protein hydrolysates via the Nrf2/HO‐1 and akt pathways

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