AD-1, a novel ginsenoside derivative, shows anti-lung cancer activity via activation of p38 MAPK pathway and generation of reactive oxygen species

Zhang, Linhui; Jia, Yongyi; Lin, Xiaofeng; Zhang, Hongquan; Dong, Xiaopeng; Zhao, Jin; Shen, Jian; Shen, Huijuan; Li, Fenfen; Yan, Xiaofeng; Li, Wei; Zhao, Yuqing; Xie, Qiang-min

doi:10.1016/j.bbagen.2013.04.008

Cited by 51 publications

(36 citation statements)

References 38 publications

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“…A p38 inhibitor (5 mg/g; SB203580; Sigma Aldrich, St Louis, MO, USA) was given intraperitoneally 1 h before irradiation based on dose-response studies that showed that 5 mg/g inhibited p38 MAPK activity [40,41]. …”

Section: Methodsmentioning

confidence: 99%

Improvement of Radiotherapy-Induced Lacrimal Gland Injury by Induced Pluripotent Stem Cell-Derived Conditioned Medium via MDK and Inhibition of the p38/JNK Pathway

Zhang

Deng

Jiao

et al. 2014

IJMS

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Radiation therapy is the most widely used and effective treatment for orbital tumors, but it causes dry eye due to lacrimal gland damage. Induced pluripotent stem cell-derived conditioned medium (iPSC-CM) has been shown to rescue different types of tissue damage. The present study investigated the mechanism of the potential radioprotective effect of IPS cell-derived conditioned medium (iPSC-CM) on gamma-irradiation-induced lacrimal gland injury (RILI) in experimental mice. In this study, we found that iPSC-CM ameliorated RILI. iPSC-CM markedly decreased radiotherapy induced inflammatory processes, predominantly through suppressing p38/JNK signaling. Further signaling pathway analyses indicated that iPSC-CM could suppress Akt (Protein Kinase B, PKB) phosphorylation. High levels of midkine (MDK) were also found in iPSC-CM and could be involved in lacrimal gland regeneration by promoting cell migration and proliferation. Thus, our study indicates that inhibiting the p38/JNK pathway or increasing the MDK level might be a therapeutic target for radiation-induced lacrimal gland injury.

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Section: Methodsmentioning

confidence: 99%

Improvement of Radiotherapy-Induced Lacrimal Gland Injury by Induced Pluripotent Stem Cell-Derived Conditioned Medium via MDK and Inhibition of the p38/JNK Pathway

Zhang

Deng

Jiao

et al. 2014

IJMS

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“…Further research has shown that 25-OCH 3 -PPD concentration-dependently inhibited the lung cancer cell viability, had no effect on normal human lung epithelial cell activity, and increased the expression of p38 and the phosphorylation of ERK. The oral administration of 25-OCH 3 -PPD (10-40 mg/kg) showed a dose-dependent inhibition of xenograft tumors without affecting body weight, but reduced the expression of CD34 VEGF and MMP-9 in tumor tissue [15].…”

Section: Chemical and Biological Studies Of 25-och 3 -Ppdmentioning

confidence: 96%

“…It can inhibit the growth and proliferation of tumor cells and induce the differentiation and apoptosis of cancer cells. The cytotoxic effects of 25-OCH 3 -PPD have been reported in several human cancer cell lines, such as human prostate cancer, pancreatic cancer, lung cancer, gastric cancer, colorectal cancer, and breast cancer cells [11][12][13][14][15][16][17]. Of all known ginsenosides tested, 25-OCH 3 -PPD showed the most potent cytotoxic effects on cancer cells.…”

Section: Introductionmentioning

confidence: 99%

25-Methoxyl-Dammarane-3β, 12β, 20-Triol, A Ginseng Saponin Derivative and an Anticancer Agent: In Vitro and In Vivo Activities, Molecular Mechanism of Action, Pharmacokinetics and Structural Modification

Wu¹,

Ding²,

Wang³

et al. 2017

Med chem (Los Angeles)

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12β, -PPD), a dammarane-type triterpene sapogenin isolated from Panax notoginseng, has shown strong antitumor effects in various human cancer cell lines, including prostate cancer, lung cancer, breast cancer, gastric cancer, colorectal cancer, pancreatic cancer, and hepatic fibrosis. This review focuses on the progress of research into 25-OCH 3 -PPD and its derivatives in cancer therapy, including in vitro and in vivo activities, structure-activity relationships, and the molecular mechanisms of action. In addition, we also summarized a method to evaluate the oral subchronic toxicity, improve oral bioavailability, and establish quality control standards for 25-OCH 3 -PPD. In this review, we have provided a detailed discussion of 25-OCH 3 -PPD and supplied a scientific reference for the research and development of 25-OCH 3 -PPD as a potential anticancer drug.

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“…The saponin exhibited 10- to 100-fold greater antitumor activities against several cancer cell lines than ginsenoside-Rg 3 , which has been listed as an adjuvant chemotherapy drug in the People’s Republic of China 11–13. The compound 25-OCH 3 -PPD has also shown inhibition of growth and proliferation, especially in breast cancer cell lines, inducing apoptosis and cell cycle arrest in the G1 phase 14.…”

Section: Introductionmentioning

confidence: 99%

Improved oral bioavailability of 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol using nanoemulsion based on phospholipid complex: design, characterization, and in vivo pharmacokinetics in rats

Zhang¹,

Zhang²,

Guo³

et al. 2016

DDDT

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The aim of the study was to improve the oral absorption of the compound 25-OCH3-PPD with poor hydrophilicity and lipophilicity. 25-OCH3-PPD-phospholipid complex was prepared by solvent evaporation, then characterized by differential scanning calorimetry, scanning electron microscopy, and infrared absorption spectroscopy. The aqueous solubility and oil–water partition coefficient were compared with the free compound. A nanoemulsion loaded with 25-OCH3-PPD-phospholipid complex was developed by dissolving the complex in water in the presence of hydrophilic surfactant under sonication. After oral administration of the nanoemulsion and the suspension of 25-OCH3-PPD in rats, the concentrations of 25-OCH3-PPD in plasma were determined by high-performance liquid chromatography–tandem mass spectrometry method. The results showed that the solubility of the complex in water and n-octanol was enhanced. The oil–water partition coefficient improved 1.7 times. Peak plasma concentration and area under the curve(0–24 h) of the nanoemulsion of 25-OCH3-PPD-phospholipid complex were higher than that of free compound by 3.9- and 3.5-folds.

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AD-1, a novel ginsenoside derivative, shows anti-lung cancer activity via activation of p38 MAPK pathway and generation of reactive oxygen species

Cited by 51 publications

References 38 publications

Improvement of Radiotherapy-Induced Lacrimal Gland Injury by Induced Pluripotent Stem Cell-Derived Conditioned Medium via MDK and Inhibition of the p38/JNK Pathway

Improvement of Radiotherapy-Induced Lacrimal Gland Injury by Induced Pluripotent Stem Cell-Derived Conditioned Medium via MDK and Inhibition of the p38/JNK Pathway

25-Methoxyl-Dammarane-3β, 12β, 20-Triol, A Ginseng Saponin Derivative and an Anticancer Agent: In Vitro and In Vivo Activities, Molecular Mechanism of Action, Pharmacokinetics and Structural Modification

Improved oral bioavailability of 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol using nanoemulsion based on phospholipid complex: design, characterization, and in vivo pharmacokinetics in rats

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AD-1, a novel ginsenoside derivative, shows anti-lung cancer activity via activation of p38 MAPK pathway and generation of reactive oxygen species

Cited by 51 publications

References 38 publications

Improvement of Radiotherapy-Induced Lacrimal Gland Injury by Induced Pluripotent Stem Cell-Derived Conditioned Medium via MDK and Inhibition of the p38/JNK Pathway

Improvement of Radiotherapy-Induced Lacrimal Gland Injury by Induced Pluripotent Stem Cell-Derived Conditioned Medium via MDK and Inhibition of the p38/JNK Pathway

25-Methoxyl-Dammarane-3β, 12β, 20-Triol, A Ginseng Saponin Derivative and an Anticancer Agent: In Vitro and In Vivo Activities, Molecular Mechanism of Action, Pharmacokinetics and Structural Modification

Improved oral bioavailability of 20(R)-25-methoxyl-dammarane-3&beta;, 12&beta;, 20-triol using nanoemulsion based on phospholipid complex: design, characterization, and in vivo pharmacokinetics in rats

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Improved oral bioavailability of 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol using nanoemulsion based on phospholipid complex: design, characterization, and in vivo pharmacokinetics in rats