Targeting signal transducer and activator of transcription 3 contributes to the solamargine-inhibited growth and -induced apoptosis of human lung cancer cells

Zhou, Yan; Tang, Qing; Zhao, Shunyu; Zhang, Fang; Li, Liuning; Wu, Wanyin; Wang, Zhiyu; Hann, Swei Sunny

doi:10.1007/s13277-014-2047-1

Cited by 30 publications

(30 citation statements)

References 27 publications

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“…46,47 A detailed mechanistic study 48 revealed that solamargine inhibited growth and induced apoptosis of non-small-cell lung cancer cells in a time-and dose-dependent manner and increased phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in a time-dependent manner. It also inhibited phosphorylation and protein expression of signal transducer and activator of transcription 3 (Stat3), which was abrogated by SB203580, a specific inhibitor of p38 MAPK, and induced protein expression of the p21 cyclin-dependent kinase inhibitors.…”

Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

Chemistry and Anticarcinogenic Mechanisms of Glycoalkaloids Produced by Eggplants, Potatoes, and Tomatoes

Friedman¹

2015

J. Agric. Food Chem.

158

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Inhibition of cancer can occur via apoptosis, a genetically directed process of cell self-destruction that involves numerous biomarkers and signaling pathways. Glycoalkaloids are nitrogen-containing secondary plant metabolites found in numerous Solanaceous plants including eggplants, potatoes, and tomatoes. Exposure of cancer cells to glycoalkaloids produced by eggplants (α-solamargine and α-solasonine), potatoes (α-chaconine and α-solanine), and tomatoes (α-tomatine) or their hydrolysis products (mono-, di-, and trisaccharide derivatives and the aglycones solasodine, solanidine, and tomatidine) inhibits the growth of the cells in culture (in vitro) as well as tumor growth in vivo. This overview comprehensively surveys and consolidates worldwide efforts to define the following aspects of these natural compounds: (a) their prevalence in the three foods; (b) their chemistry and structure-activity relationships; (c) the reported factors (biomarkers, signaling pathways) associated with apoptosis of bone, breast, cervical, colon, gastric, glioblastoma, leukemia, liver, lung, lymphoma, melanoma, pancreas, prostate, and squamous cell carcinoma cell lines in vitro and the in vivo inhibition of tumor formation and growth in fish and mice and in human skin cancers; and (d) future research needs. The described results may make it possible to better relate the structures of the active compounds to their health-promoting function, individually, in combination, and in food, and allow the consumer to select glycoalkaloid-containing food with the optimal content of nontoxic beneficial compounds. The described findings are expected to be a valuable record and resource for further investigation of the health benefits of food-related natural compounds.

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Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

Chemistry and Anticarcinogenic Mechanisms of Glycoalkaloids Produced by Eggplants, Potatoes, and Tomatoes

Friedman¹

2015

J. Agric. Food Chem.

158

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“…Compared with 6-paradol which found in grains of paradise seeds, 6-shogaol was more effective [8]. 6-shogaol may also prevent the growth of human pancreatic tumors and has a high responsive to gemcitabine by suppressing inflammatory pathways linked to tumorigenesis [9].…”

Section: Introductionmentioning

confidence: 97%

Extraction of Phytochemicals from Grains of Paradise Using Supercritical Carbon Dioxide

Ono¹,

Kawamoto²,

Uemori³

et al. 2017

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Abstract. Supercritical carbon dioxide (SCCO2) is one of the green methods to extract plant matters substances. In this study, SCCO2 has been applied as a media to extract the grains of paradise seeds substances at temperatures of 40 -80 o C and pressures of 20 -40 MPa using a semi-continuous flow-type system. Results of FT-IR spectra analysis showed that the grains of paradise seeds substances were extracted by SCCO2. The SEM images of the grains of paradise seeds residues also showed that the physical changes of the grains of paradise seeds surface occurred after SCCO2 extraction. The main compounds in extracts were gingerols, shogaols, and paradols. However, the GC-MS may only identify paradol compounds due to gingerols, shogaols, and paradols are homologous series of phenolic ketones and paradols was more stable than gingerols and shogaols. The yields of gingerols, shogaols, and paradols were 9.12, 3.90, and 4.42 mg/g sample, respectively and affected by extraction temperatures and/or extraction pressures.

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“…Several reports showed that inhibition of Stat3 suppressed the growth of cancer cells and enhanced the sensitivity to anticancer agents in several cancer types [16-18]. Thus, targeting Stat3 has potential for prevention and treatment of cancers [17, 19]. Stat3 is persistently activated in NSCLC [14, 20], overexpression of Stat3 resulted in poor prognosis, thus, high activation of p-Stat3 was considered as a diagnostic marker in patients with NSCLC [16].…”

Section: Introductionmentioning

confidence: 99%

Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells

Xiao¹,

Zheng²,

Wu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Atractylodes macrocephula Koidz is an important ingredient in traditional Chinese herbs. One major bioactive compound, atractylenolide-1 (ATL-1), was reported to have anti-inflammatory and anti-tumor activities. However, the underlying molecular mechanism associated to this has not been well elucidated. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Western blot analysis was performed to examine the phosphorylation and protein expression of extracellular signaling-regulated kinase 1/2 (ERK1/2), signal transducer and activator of transcription 3 (Stat3), 3-phosphoinositide dependent protein kinase-1 (PDK1) and transcription factor SP1. QRT-PCR was used to examine the mRNA levels of PDK1 gene. Exogenously expressions of Stat3, PDK1 and SP1 were carried out by transient transfection assays. PDK1 promoter activity was measured by Secrete-Pair Dual Luminescence Assay Kit. A nude mice xenograft model was used to confirm the findings in vitro. Results: We showed that ATL-1 inhibited human lung cancer cell growth and induced cell cycle arrest. Furthermore, we found that ATL-1 stimulated phosphorylation of ERK1/2, inhibited phosphorylation and protein expressions of Stat3 and SP1; the latter were abrogated in the presence of MEK/ERK inhibitor PD98059. Moreover, ATL-1 reduced the protein, mRNA expression and promoter activity of PDK1. Intriguingly, exogenously expressed Stat3 and SP1 overcame ATL-1-inhibited SP1 and Stat3, and PDK1 protein expressions, respectively. Moreover, overexpression of PDK1 resisted the ATL-1-inhibited lung cancer cell growth. In consistent with the results in vitro, ATL-1 inhibited tumor growth, protein expressions of Stat3, SP1 and PDK1, and induced phosphorylation of ERK1/2 in vivo. Conclusion: In summary, our results show that ATL-1 inhibits lung cancer cell growth through activation of ERK1/2, followed by suppressing SP1 protein expression. ATL-1 also reduces phosphorylation and protein levels of Stat3. These are mutual regulation between Stat3 and SP1 proteins affected by ATL-1. This ultimately suppresses PDK1 gene expression. This study reveals a novel mechanism by which ATL-1 inhibits growth of lung cancer cells. Thus, targeting PDK1 pinpoints a potential in the lung cancer treatment.

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Targeting signal transducer and activator of transcription 3 contributes to the solamargine-inhibited growth and -induced apoptosis of human lung cancer cells

Cited by 30 publications

References 27 publications

Chemistry and Anticarcinogenic Mechanisms of Glycoalkaloids Produced by Eggplants, Potatoes, and Tomatoes

Chemistry and Anticarcinogenic Mechanisms of Glycoalkaloids Produced by Eggplants, Potatoes, and Tomatoes

Extraction of Phytochemicals from Grains of Paradise Using Supercritical Carbon Dioxide

Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells

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