Involvement of Reactive Oxygen Species in the Hepatorenal Toxicity of Actinomycin V In Vitro and In Vivo

Jia, Fu-Juan; Han, Ze‐Guang; Ma, Jiahui; Jiang, Shengbing; Zhao, Xing‐Ming; Ruan, Hang; Xie, Wenrui; Li, Xia

doi:10.3390/md18080428

Cited by 4 publications

(4 citation statements)

References 27 publications

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“…It also induced apoptosis in a p53-mediated manner in the human non-small-cell lung cancer cell line A549 [5]. Further studies proved that Act V presented considerably stronger efficacy for cancer cells and less hepatorenal toxicity compared with Act D in vitro and in vivo, making Act V a more potent candidate to replace Act D [6]. Moreover, supercritical fluid chromatography has been applied to isolate Act V from Act D with higher efficacy and less time, making Act V a more accessible and economical drug candidate [7].…”

Section: Introductionmentioning

confidence: 97%

Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells

et al. 2021

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Actinomycin (Act) V, an analogue of Act D, presented stronger antitumor activity and less hepatorenal toxicity than Act D in our previous studies, which is worthy of further investigation. We hereby report that Act V induces apoptosis via mitochondrial and PI3K/AKT pathways in colorectal cancer (CRC) cells. Act V-induced apoptosis was characterized by mitochondrial dysfunction, with loss of mitochondria membrane potential (MMP) and cytochrome c release, which then activated cleaved caspase-9, cleaved caspase-3, and cleaved PARP, revealing that it was related to the mitochondrial pathway, and the apoptotic trendency can be reversed by caspase inhibitor Z-VAD-FMK. Furthermore, we proved that Act V significantly inhibited PI3K/AKT signalling in HCT-116 cells using cell experiments in vitro, and it also presented a potential targeted PI3Kα inhibition using computer docking models. Further elucidation revealed that it exhibited a 28-fold greater potency than the PI3K inhibitor LY294002 on PI3K inhibition efficacy. Taken together, Act V, as a superior potential replacement of Act D, is a potential candidate for inhibiting the PI3K/AKT pathway and is worthy of more pre-clinical studies in the therapy of CRC.

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Section: Introductionmentioning

confidence: 97%

Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells

et al. 2021

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“…Furthermore, quinones are also known to boost reactive oxygen species (ROS), which are a proven source of tight junction protein degradation. ROS release was directly proportional to cell tight junction damage and lower than usual TEER values in a previous study [19,28].…”

Section: Real-time Monitoring Of Liver Tumor Mpsmentioning

confidence: 54%

“…Life 2022, 12, x FOR PEER REVIEW 6 of 11 source of tight junction protein degradation. ROS release was directly proportional to cell tight junction damage and lower than usual TEER values in a previous study [19,28].…”

Section: Effect Of a Cappadocicum On Liver Function Testsmentioning

confidence: 54%

Study of the Anticancer Potential of Plant Extracts Using Liver Tumor Microphysiological System

Farooqi

Sammantasinghar

Kausar

et al. 2022

Life

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Background: Plants have been considered a vital source of modern pharmaceutics since the paleolithic age. Contemporary chemotherapeutic drugs for cancer therapy are chemical entities sourced from plants. However, synthetic drugs or their derivatives come with severe to moderate side effects for human health. Hence, the quest to explore and discover plant-based novel anticancer drugs is ongoing. Anticancer activities are the primary method to estimate the potential and efficacy of an extract or compound for drug discovery. However, traditional in vitro anticancer activity assays often show poor efficacy due to the lack of in-vivo-like cellular environment. In comparison, the animal-based in vivo assays lack human genetic makeup and have ethical concerns. Aim: This study aimed to overcome the limitations of traditional cell-culture-based anticancer assays and find the most suitable assay for anticancer activity of plant extracts. We first reported utilizing a liver tumor microphysiological system in the anticancer effect assessment of plant extracts. Methodology: Methanolic extracts of Acer cappadocicum Gled were used to assess anticancer activity against liver tumor microphysiological system (MPS), and cell viability, liver function tests, and antioxidant enzyme activities were performed. Additionally, an embedded transepithelial electrical resistance sensor was utilized for the real-time monitoring of the liver tumor MPS. The results were also compared with the traditional cell culture model. Results: The study demonstrated the superiority of the TEER sensor-based liver tumor MPS by its better anticancer activity based on cell viability and biomarker analysis compared to the traditional in vitro cell culture model. The anticancer effects of the plant extracts were successfully observed in real time, and methanolic extracts of Acer cappadocicum Gled increased the alanine transaminase and aspartate aminotransferase secretion, which may reveal the different mechanisms of these extracts and suggest a clue for the future molecular study of the anticancer pathways. Conclusion: Our results show that the liver tumor microphysiological system could be a better platform for plant-based anticancer activity assessment than traditional cell culture models.

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“…Exogenous BmApoD1 addition to BmN cells (B. mori ovary cells) also increased survival upon challenge with 1mM H 2 O 2 treatment and also inhibited actinomycin D-induced apoptosis [26]. The mechanism preventing cell death upon Actinomycin-D treatment might be linked to the reduction in lipid oxidation as treatment of HEK293T and LO-2 cells with actinomycin-D increases LPO, which is decreased by ApoD overexpression in many cell types [113]…”

Section: Insect Modelsmentioning

confidence: 99%

Apolipoprotein D in Oxidative Stress and Inflammation

et al. 2023

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Apolipoprotein D (ApoD) is lipocalin able to bind hydrophobic ligands. The APOD gene is upregulated in a number of pathologies, including Alzheimer’s disease, Parkinson’s disease, cancer, and hypothyroidism. Upregulation of ApoD is linked to decreased oxidative stress and inflammation in several models, including humans, mice, Drosophila melanogaster and plants. Studies suggest that the mechanism through which ApoD modulates oxidative stress and regulate inflammation is via its capacity to bind arachidonic acid (ARA). This polyunsaturated omega-6 fatty acid can be metabolised to generate large variety of pro-inflammatory mediators. ApoD serves as a sequester, blocking and/or altering arachidonic metabolism. In recent studies of diet-induced obesity, ApoD has been shown to modulate lipid mediators derived from ARA, but also from eicosapentaenoic acid and docosahexaenoic acid in an anti-inflammatory way. High levels of ApoD have also been linked to better metabolic health and inflammatory state in the round ligament of morbidly obese women. Since ApoD expression is upregulated in numerous diseases, it might serve as a therapeutic agent against pathologies aggravated by OS and inflammation such as many obesity comorbidities. This review will present the most recent findings underlying the central role of ApoD in the modulation of both OS and inflammation.

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Involvement of Reactive Oxygen Species in the Hepatorenal Toxicity of Actinomycin V In Vitro and In Vivo

Cited by 4 publications

References 27 publications

Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells

Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells

Study of the Anticancer Potential of Plant Extracts Using Liver Tumor Microphysiological System

Apolipoprotein D in Oxidative Stress and Inflammation

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