Deguelin inhibits proliferation and migration of human pancreatic cancer cells in vitro targeting hedgehog pathway

Zheng, Wen; Lu, Shiliu; Cai, Haolei; Kang, Muxing; Qin, Wenjie; Li, Chao; Wu, Yulian

doi:10.3892/ol.2016.4928

Cited by 24 publications

(17 citation statements)

References 34 publications

(33 reference statements)

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“…Consistently, a recent study showed that deguelin could inhibit cancer cells growth with apoptosis being involved [17,25,26]. Furthermore, we found that deguelin promotes accumulation of autophagosomes.…”

Section: Discussionsupporting

confidence: 90%

Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin

Zhao

Zhang

et al. 2017

IJMS

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Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.

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Section: Discussionsupporting

confidence: 90%

Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin

Zhao

Zhang

et al. 2017

IJMS

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“…Non‐small cell lung cancer accounts for the major percentage of lung cancer cases and has a poor prognosis. In recent years, drug resistance in tumor treatment has been a concern for patients; however, more in‐depth studies on anti‐tumor mechanisms and components, such as deguelin, are being studied in different cancers . In this study, we demonstrated that deguelin inhibited NSCLC cell metastasis and EMT by downregulating NEK2 expression.…”

Section: Discussionmentioning

confidence: 67%

“…Deguelin, a rotenoid extracted from Mundulea sericea , has been documented to possess anti‐tumor activities for several cancers, including pancreatic, lung, breast and colon cancers . Accumulating evidences have shown that deguelin is involved in different biological processes, such as apoptosis, proliferation, and migration/invasion . A recent study showed that low‐dose deguelin inhibited oral cancer migration and invasion by regulating tumor necrosis factor‐α‐induced nuclear factor‐κB activity and matrix metallpproteinase‐2 (MMP‐2), and in human osteosarcoma cells by inhibiting MMP‐2/MMP‐9 expression .…”

Section: Introductionmentioning

confidence: 99%

Deguelin inhibits epithelial‐to‐mesenchymal transition and metastasis of human non‐small cell lung cancer cells by regulating NIMA‐related kinase 2

et al. 2017

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BackgroundNon‐small cell lung cancer is a lethal malignancy with a high mortality rate. Deguelin displays an anti‐tumor effect and inhibits metastasis in various cancers. The aberrant expression of NIMA‐related kinase 2 (NEK2) indicates poor prognosis and induces epithelial‐to‐mesenchymal transition (EMT) and metastasis processes. However, the underlying mechanism between deguelin and NEK2 has remained elusive.Methods NSCLC cell lines were treated with deguelin. Wound‐healing and invasion assays were applied to study the inhibitory effect of deguelin on NSCLC cells. EMT markers, E‐cadherin and Vimentin, were also detected by Western blot. NEK2 protein and messenger RNA expression levels were evaluated when NSCLC cells were treated with different concentrations of deguelin. The effect of NEK2 on NSCLC cell metastasis was evaluated through NEK2 knockdown. To investigate whether deguelin induced EMT by regulating NEK2, we overexpressed NEK2 in both NCI‐H520 and SK‐MES‐1 cell lines, and then used real time‐PCR to study the E‐cadherin and Vimentin messenger RNA expression in both NSCLC cells.ResultsDeguelin inhibited migration and invasion processes in NSCLC cell lines and decreased NEK2 expression in a concentration‐dependent manner. Furthermore, NEK2 knockdown inhibited NSCLC cell migration and invasion. Finally, overexpressing NEK2 in NCI‐H520 and SK‐MES‐1 cells could restore the inhibition of metastasis induced by deguelin.ConclusionsDeguelin could inhibit EMT and metastasis, while overexpression of NEK2 promotes these processes. Deguelin could decrease NEK2 expression, while NEK2 overexpression could restore deguelin‐induced inhibition of metastasis.

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“…Briefly, deguelin impedes carcinogenesis by 1) inducing cell apoptosis, 2) inhibiting tumor cell propagation, and 3) preventing malignant transformation of tumors. 16,17 Crucial oncogenic pathways likely targeted by deguelin are the phosphoinositide 3-kinase (PI3K)/Akt pathway, [18][19][20][21][22][23][24][25][26] the Wnt signaling pathway, 27,28 the epidermal growth factor receptor (EGFR) and c-Met signaling pathway, 29 the epithelial-to-mesenchymal transition (EMT) pathway, 30 the hedgehog signaling pathway, 31,32 and angiogenesis-related pathways. 33 In addition, deguelin has been identified as an Aurora B kinase inhibitor that exhibits a potent antitumor effect in human esophageal squamous cell carcinoma.…”

Section: Key Proliferative and Angiogenic Pathways Targeted By Deguelinmentioning

confidence: 99%

Biopharmacological considerations for accelerating drug development of deguelin, a rotenoid with potent chemotherapeutic and chemopreventive potential

Varughese

Lam

Marican

et al. 2019

Cancer

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Deguelin is a rotenoid compound that exists in abundant quantities in the bark, roots, and leaves of the Leguminosae family of plants. An analysis of evidence from both in vitro and in vivo studies suggests that deguelin displays potent anticancer activity against multiple cancer types and exhibits chemopreventive potential in Akt‐inducible transgenic mouse models. Deguelin appears to impede carcinogenesis by enhancing cell apoptosis and hindering malignant transformation and tumor cell propagation. Crucial oncogenic pathways likely targeted by deguelin include the epithelial‐to‐mesenchymal transition; angiogenesis‐related pathways; and the phosphoinositide 3‐kinase/Akt, Wnt, epidermal growth factor receptor, c‐Met, and hedgehog signal transduction cascades. This review article provides a comprehensive summary of current preclinical research featuring deguelin as a leading chemotherapeutic and chemopreventive compound, and it highlights the importance of identifying companion molecular biomarkers and performing systemic pharmacokinetic studies for accelerating the process of developing deguelin as a clinical anticancer agent.

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Deguelin inhibits proliferation and migration of human pancreatic cancer cells in vitro targeting hedgehog pathway

Cited by 24 publications

References 34 publications

Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin

Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin

Deguelin inhibits epithelial‐to‐mesenchymal transition and metastasis of human non‐small cell lung cancer cells by regulating NIMA‐related kinase 2

Biopharmacological considerations for accelerating drug development of deguelin, a rotenoid with potent chemotherapeutic and chemopreventive potential

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