Dual role of acetaminophen in promoting hepatoma cell apoptosis and kidney fibroblast proliferation

Yu, Yung Luen; Yiang, Giou Teng; Chou, Pei Lun; Tseng, Hsu Hung; Wu, Tsai Kun; Hung, Yung‐Jr; Lin, Pei Shiuan; Lin, Shu Yu; Liu, Hsiao Chun; Chang, Wei; Wei, Chyou Wei

doi:10.3892/mmr.2014.2085

Cited by 33 publications

(47 citation statements)

References 76 publications

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“…Determination of cell viability. Cell viability was measured by the MTT assay described in previous studies (40,41). Briefly, cells were cultured into 96-well plates (5x10 3 cells/well).…”

Section: Methodsmentioning

confidence: 99%

“…Observation of DNA fragmentation and nuclear condensation. Nuclear condensation and DNA fragmentation, cardinal characteristics of apoptotic cells, were observed using Hoechst 33342 nuclear staining (40,41). Control and experimental (MTX and/or vitamin C-treated) cells were incubated in Hoechst 33342 (10 µg/ml) for 5 min.…”

Section: Measurements Of Intracellular H 2 O 2 and Omentioning

confidence: 99%

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Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Liu

et al. 2017

Oncology Reports

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Methotrexate (MTX) is widely used as both an anticancer and anti-rheumatoid arthritis drug. Although MTX has been used to inhibit the growth of many cancer cells, it cannot effectively inhibit growth of triple-negative breast cancer cells (TNBC cells). Vitamin C is an antioxidant that can prevent oxidative stress. In addition, vitamin C has been applied as adjunct treatment for growth inhibition of cancer cells. Recent studies indicated that combined treatment with vitamin C and MTX may inhibit MCF-7 and MDA-MB-231 breast cancer cell growth through G2/M elongation. However, the mechanisms remain unknown. The aim of the present study was to determine whether combined treatment with low-dose vitamin C and MTX inhibits TNBC cell growth and to investigate the mechanisms of vitamin C/MTX-induced cytotoxicity. Neither low-dose vitamin C alone nor MTX alone inhibited TNBC cell growth. However, combined low-dose vitamin C and MTX had synergistic anti-proliferative/cytotoxic effects on TNBC cells. In addition, co-treatment increased H2O2 levels and activated both caspase-3 and p38 cell death pathways.

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“…Determination of cell viability. Cell viability was measured by the MTT assay described in previous studies (40,41). Briefly, cells were cultured into 96-well plates (5x10 3 cells/well).…”

Section: Methodsmentioning

confidence: 99%

Section: Measurements Of Intracellular H 2 O 2 and Omentioning

confidence: 99%

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Liu

et al. 2017

Oncology Reports

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“…Acetaminophen is an antipyretic and analgesic agent, similar to NSAIDs, and has been shown to exert significant anticancer effects in tumor cells. However, long-term acetaminophen administration can lead to serious hepatotoxicity as a main side effect (Liang et al, 2012;Posadas et al, 2012;Yu et al, 2014). Therefore, determining the appropriate acetaminophen treatment concentration should be the main consideration in therapeutic decisions.…”

Section: Original Articlementioning

confidence: 99%

Improving Combination Cancer Therapy by Acetaminophen and Romidepsin in Non-small Cell Lung Cancer Cells

Lee

Park

Kim

2019

BSL

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Combination chemotherapy is more effective than mono-chemotherapy and is widely used in clinical practice for enhanced cancer treatment. In this study, we investigated the potential synergistic effects of acetaminophen, a common component in many cold medicines, and romidepsin, a histone deacetylase (HDAC) inhibitor, in the A549 non-small cell lung cancer (NSCLC) cell line. The combination of acetaminophen and romidepsin also exerted significant cytotoxicity and apoptosis induced by activation of caspase-3 on tumor cells in vitro. Moreover, combination therapy significantly induced increased production of chemokines that stimulate migration of activated T-cells into tumor cells. This mechanism can lead to active T-cell mediated anti-tumor immunity in addition to the direct cytotoxic chemotherapeutic effect. Activated T-cells led to enhanced cytotoxicity in drug-treated A549 cells through interaction with tumor cells. These results suggested that the interaction between the two drugs is synergistic and significant. In conclusion, our data showed that the use of romidepsin and low concentrations acetaminophen could induce effective anti-tumor effects via enhanced tumor immune and direct cytotoxic chemotherapeutic responses. The combination of acetaminophen with romidepsin should be considered as a promising strategy for the treatment of lung cancer.

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“…Oxidative stress has been shown to be one of the important factors in APAP‐induced AKI (Yu et al, ). The ROS in the human body accumulates through the enzyme and non‐enzymatic systems (Pejin et al, ).…”

Section: Introductionmentioning

confidence: 99%

Sika deer antler protein against acetaminophen‐induced oxidative stress and apoptosis in HK‐2 cells via activating Nrf2/keap1/HO‐1 pathway

Ruan

Wang

et al. 2019

J Food Biochem

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Nf-E2-related transcription factor 2 (Nrf2) helps cells fight oxidative stress events in vivo and in vitro by promoting the expression of antioxidants and detoxification enzymes. The necessary factors regulating Nrf2 activity and stability during analgesic nephropathy are not fully understood. Our results suggest that acetaminophen produces nephrotoxicity in HK-2 cells by inhibiting keap1 degradation. APAP subsided Nrf2 nuclear accumulation by inhibition of keap1 degradation, thereby reducing the binding of Nrf2 to ARE, leading to the loss of expression of antioxidant proteins such as HO-1, inducing a series of oxidative stress and apoptosis events. Therefore, Nrf2/ keap1/HO-1 signal transduction pathway has a poor prognosis during analgesic nephrotoxicity. Sika deer antler protein (SDAPR) significantly prevented APAP-induced HK-2 cell damage by constitutively stabilized Nrf2 nuclear retention. Excess APAP leads to a decrease in Nrf2 nuclear translocation, leading to severe oxidative stress, increasing the levels of GSH and MDA in HK-2 cells, and reducing the enzyme activities of SOD and CAT in HK-2 cells. Increased biomarker levels of acute kidney injury (AKI) in HK-2 cells, including kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and cystatin C, decrease the mitochondrial membrane potential in HK-2 cells, and cause mitochondrial dysfunction, it also reduced the ratio of mitochondria-associated apoptotic protein Bax/Bcl-2, leading to cell apoptosis. SDAPR dose dependently accorded protection against acetaminophen-induced nephrotoxicity, oxidative damage, and cell apoptosis by its molecular intervention with Nrf2/ keap1/HO-1 pathway via keap1 degradation. Practical applicationsIn this paper, we investigated the protective effect of SDAPR on APAP-induced AKI in HK-2 cells, and briefly explained its possible mechanism of action, providing a basis for future clinical trials and the development of anti-APAP AKI drugs. K E Y W O R D S acetaminophen, apoptosis, HK-2 cell, Nrf2/keap1/HO-1 pathway, oxidative stress, sika deer antler protein How to cite this article: Ruan H, Wang L, Wang J, et al. Sika deer antler protein against acetaminophen-induced oxidative stress and apoptosis in HK-2 cells via activating Nrf2/keap1/ HO-1 pathway. J Food Biochem. 2019;43:e13067.

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Dual role of acetaminophen in promoting hepatoma cell apoptosis and kidney fibroblast proliferation

Cited by 33 publications

References 76 publications

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Improving Combination Cancer Therapy by Acetaminophen and Romidepsin in Non-small Cell Lung Cancer Cells

Sika deer antler protein against acetaminophen‐induced oxidative stress and apoptosis in HK‐2 cells via activating Nrf2/keap1/HO‐1 pathway

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