The ester derivatives obtained by C-ring modification of podophyllotoxin induce apoptosis and inhibited proliferation in PC-3M cells via down-regulation of PI3K/Akt signaling pathway

Zhao, Yan; Li, Danyao; Wei, Minggang; Du, Rui; Yan, Zhaowei

doi:10.1016/j.bmcl.2021.128174

Cited by 11 publications

(12 citation statements)

References 18 publications

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“…Importantly, Akt, as a key protein in the downstream signaling pathway of PI3K, participates in the regulation of cell proliferation, metabolism, apoptosis, and migration. 31 Much research has suggested that excessive accumulation of ROS promotes the translocation of apoptotic proteins to mitochondria by inhibiting the activation of the PI3K/Akt signaling pathway. 32 After Akt is activated, its downstream target proteins (such as Bcl-2 and Bax) are regulated, while inhibiting the activity of the proteolytic enzyme caspase 9, preventing the initiation of the apoptotic cascade and inhibiting cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…ABL treatment gradually restored abnormal nuclear morphology and inhibited hepatocyte apoptosis. Importantly, Akt, as a key protein in the downstream signaling pathway of PI3K, participates in the regulation of cell proliferation, metabolism, apoptosis, and migration . Much research has suggested that excessive accumulation of ROS promotes the translocation of apoptotic proteins to mitochondria by inhibiting the activation of the PI3K/Akt signaling pathway .…”

Section: Discussionmentioning

confidence: 99%

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1-O-Actylbritannilactone Ameliorates Alcohol-Induced Hepatotoxicity through Regulation of ROS/Akt/NF-κB-Mediated Apoptosis and Inflammation

et al. 2022

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1- O -Acetylbritannilactone (ABL) is a marker component of Inula britannica L. and is reported to exhibit multiple pharmacological activities, including antiaging, anti-inflammatory, and antidiabetic properties. Although the protective effect of Inula britannica L. on animal models of liver injury has been widely reported, the effect of ABL on alcohol-induced liver damage has not been confirmed. The present study was designed to investigate the protective effect of ABL against alcohol-induced LO2 human normal liver cell injury and to further clarify the underlying mechanism. Our results revealed that ABL at concentrations of 0.5, 1, and 2 μM could remarkably suppress the decreased viability of LO2 cells stimulated by alcohol. In addition, ABL pretreatment improved alcohol-induced oxidative damage by decreasing the level of reactive oxygen species (ROS) and the excessive consumption of glutathione peroxidase (GSH-Px), while increasing the level of catalase (CAT) in LO2 cells. Moreover, Western blotting analysis showed that ABL pretreatment activated protein kinase B (Akt) phosphorylation, increased downstream antiapoptotic protein Bcl-2 expression, and decreased the phosphorylation level of the caspase family including caspase 9 and caspase 3 proteins, thereby attenuating LO2 cell apoptosis. Importantly, we also found that ABL significantly inhibits the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the secretion of proinflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin (IL-1β). In conclusion, the current research clearly suggests that the protective effect of ABL on alcohol-induced hepatotoxicity may be achieved in part through regulation of the ROS/Akt/NF-κB signaling pathway to inhibit inflammation and apoptosis in LO2 cells. (The article path map has not been seen.)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

1-O-Actylbritannilactone Ameliorates Alcohol-Induced Hepatotoxicity through Regulation of ROS/Akt/NF-κB-Mediated Apoptosis and Inflammation

et al. 2022

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“…Besides, AKT is a key protein in the downstream signaling pathway of phosphoinositide 3-kinase that regulates cell proliferation, metabolism, apoptosis, and motivation. 46 It was reported that chlormethiazole, a CYP2E1 inhibitor, and N-acetyl-L-cysteine, a precursor of glutathione, could reduce lipid accumulation in livers via an upregulation of P-AKT. 47 Previous studies also reported that hesperidin and CLHs could downregulate proinflammatory/profibrotic responses and stimulate anti-inflammatory cytokine secretion in livers of CCl 4 treated rats, 48 thioacetamide treated rats, 34 and high-fat diet-fed mice.…”

Section: Effects Of Clh-based Supplement On Growth Performance Organ ...mentioning

confidence: 99%

A functional chicken‐liver hydrolysate‐based supplement ameliorates alcohol liver disease via regulation of antioxidation, anti‐inflammation, and antiapoptosis

Wu,

Lin,

Kao

et al. 2023

Environmental Toxicology

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Tons of broiler livers are produced yearly in Taiwan but always considered waste. Our team has successfully patented and characterized a chicken‐liver hydrolysate (CLH) with several biofunctions. Chronic alcohol consumption causes hepatosteatosis or even hepatitis, cirrhosis, and cancers. This study was to investigate the hepatoprotection of CLH‐based supplement (GBHP01™) against chronic alcohol consumption. Results showed that GBHP01™ could reduce (p < .05) enlarged liver size, lipid accumulation/steatosis scores, and higher serum AST, ALT, γ‐GT, triglyceride, and cholesterol levels induced by an alcoholic liquid diet. GBHP01™ reduced liver inflammation and apoptosis in alcoholic liquid‐diet‐fed mice via decreasing TBARS, interleukin‐6, interleukin‐1β, and tumor necrosis factor‐α levels, increasing reduced GSH/TEAC levels and activities of SOD, CAT and GPx, as well as downregulating CYP2E1, BAX/BCL2, Cleaved CASPASE‐9/Total CASPASE‐9 and Active CASPASE‐3/Pro‐CASPASE‐3 (p < .05). Furthermore, GBHP01™ elevated hepatic alcohol metabolism (ADH and ALDH activities) (p < .05). In conclusion, this study prove the hepatoprotection of GBHP01™ against alcohol consumption.

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“…However, clinical therapy is severely limited because of systemic toxicity effects. Recently, modification of podophyllotoxin has enabled clinical application; the most clinically used drugs are etoposide and teniposide, which are glycosylated at the C-4 position 59 , 60 . Because podophyllotoxin is an effective targeted microtubule drug, drug development has continued.…”

Section: Microtubulementioning

confidence: 99%

Anti-tumor pharmacology of natural products targeting mitosis

et al. 2022

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Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation of cancer cells is one of cancer’s main characteristics, which is closely associated with abnormal mitosis. Targeting mitosis is an effective method for cancer treatment. This review summarizes several natural products with anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, the main disadvantages of several typical compounds, including drug resistance, toxicity to non-tumor tissues, and poor aqueous solubility and pharmacokinetic properties, are also discussed, together with strategies to address them. Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer.

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The ester derivatives obtained by C-ring modification of podophyllotoxin induce apoptosis and inhibited proliferation in PC-3M cells via down-regulation of PI3K/Akt signaling pathway

Cited by 11 publications

References 18 publications

1-O-Actylbritannilactone Ameliorates Alcohol-Induced Hepatotoxicity through Regulation of ROS/Akt/NF-κB-Mediated Apoptosis and Inflammation

1-O-Actylbritannilactone Ameliorates Alcohol-Induced Hepatotoxicity through Regulation of ROS/Akt/NF-κB-Mediated Apoptosis and Inflammation

A functional chicken‐liver hydrolysate‐based supplement ameliorates alcohol liver disease via regulation of antioxidation, anti‐inflammation, and antiapoptosis

Anti-tumor pharmacology of natural products targeting mitosis

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