Anti-tumor effects of Atractylenolide I on bladder cancer cells

Yu, Ran; Yu, Bixia; Chen, Junfeng; Lv, Xiu‐Yi; Yan, Zejun; Cheng, Yufeng; Ma, Qi

doi:10.1186/s13046-016-0312-4

Cited by 83 publications

(76 citation statements)

References 34 publications

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“…Atractylenolide 1 (ATL-1), ATL-2, and ATL-3 are the major bioactive components of medicinal herb Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala) and demonstrate anti-inflammatory and anticancer activities. However, the in-depth molecular mechanism underlying the anti-cancer effects of the major active compound, ATL-1, still remained unclear [8, 45, 48]. In the present study, we provided evidence demonstrating the anti-lung cancer effects of ATL-l.…”

Section: Discussionsupporting

confidence: 64%

“…In the present study, we provided evidence demonstrating the anti-lung cancer effects of ATL-l. The doses of ATL-1 in the current study were similar or even lower than those reported by others demonstrating substantial anti-cancer responses in several cancer types [13, 45, 49]. Our results showed that ATL-1 inhibited lung cancer cell growth through ERK1/2-mediated suppression of Stat3 and SP1 protein expressions.…”

Section: Discussionmentioning

confidence: 41%

“…Mice bearing xenografted tumor was given by intraperitoneal different doses of ATL-1 daily (25 and 75 mg/kg, respectively) [45] for up to 20 days. We found that the high dose ATL-1-treated mice showed a significant delayed tumor growth without any severe adverse events as compared to that in the control group (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…A549-Luc cells (1x10 6 cells) were given subcutaneously into mice and the xenografts were allowed to grow for 5 days when the initial measurement was available (1000-1500 mm 3 ). The mice were randomly divided into three groups: control, low (25 mg/kg) and high doses (75 mg/kg) of ATL-1 groups, which were given daily intraperitoneal injection for up to 20 days (n=10/group) as reported in other study [45]. …”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 41%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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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“…and exerts a wide range of pharmacological activities, including anti-inflammatory (11,12), anti-tumor (13,14) and anti-angiogenic effects (15). A previous study has implied a potential anti-depressive activity of AT-I (16).…”

Section: Introductionmentioning

confidence: 99%

Anti-depressant-like effect of atractylenolide I in a mouse model of depression induced by chronic unpredictable mild stress

Gao

Zhu

et al. 2017

Exp Ther Med

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Abstract. Atractylenolide I (AT-I), a major component of the rhizoma of Atractylodes macrocephala Koidz., exerts a wide range of activities. The purpose of the present study was to investigate the anti-depressant-like effect of AT-I in a mouse model of chronic unpredictable mild stress (CUMS), and to explore the possible molecular mechanism involved. It was revealed that AT-I significantly ameliorated CUMS-induced depressive-like behaviors, as evidenced by increased sucrose preference as well as shortened immobility time in the forced swimming and the tail suspension test. In addition, AT-I reduced CUMS-induced decreases in the concentrations of serotonin and norepinephrine in the hippocampus. Furthermore, AT-I inhibited the activation of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome as well as the concentration of the pro-inflammatory cytokine interleukin (IL)-1β in the hippocampi of mice subjected to CUMS. In conclusion, the results of the present study suggested that AT-I exerts anti-depressant-like effects in a CUMS-induced model of depression in mice, the molecular mechanism of which is associated with the inhibition of NLRP3 inflammasome activation to decrease IL-1β production.

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OSU‐T315 and doxorubicin synergistically induce apoptosis via mitochondrial pathway in bladder cancer cells

Ren

Chen

et al. 2022

Cell Biology International

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Bladder cancer (BC) is a common urological malignancy that still lacks an effective treatment. Doxorubicin (Dox) has been widely used in the treatment of various cancers, including BC. However, chemoresistance often hampers the clinical application of Dox, therefore, it is necessary to develop effective strategies to improve its efficacy. By using high-throughput screening, we identified OSU-T315, an integrin-linked kinase (ILK) inhibitor, that can augment the cytotoxicity of Dox against BC cells. We found that OSU-T315 and Dox synergistically induce apoptosis of BC cells via mitochondrial pathway in a caspase-dependent. Mechanically, it was found that OSU-T315 and Dox synergistically induced activation of Bax which is critical for the induction of apoptosis. Moreover, it was also found that the downregulation of BCL-2 and MCL-1 is essential for the activation of BAX induced by OSU-T315 and Dox.OSU-T315 was found to downregulate MCL-1 via the GSK-3β/FBXW7 axis in BC cells. Our findings suggest that combined treatment with OSU-T315 and Dox may be a promising strategy to treat BC.

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Anti-tumor effects of Atractylenolide I on bladder cancer cells

Cited by 83 publications

References 34 publications

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

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

Anti-depressant-like effect of atractylenolide I in a mouse model of depression induced by chronic unpredictable mild stress

OSU‐T315 and doxorubicin synergistically induce apoptosis via mitochondrial pathway in bladder cancer cells

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