Deguelin, a novel anti-tumorigenic agent targeting apoptosis, cell cycle arrest and anti-angiogenesis for cancer chemoprevention

Wang, Ying; Ma, Wenxue; Wen-ling, Zheng

doi:10.3892/mco.2012.36

Cited by 73 publications

(53 citation statements)

References 36 publications

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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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“…Although the suppression of multiple protein kinases, transcription factors and signal transduction pathways are involved in deguelin-mediated anti-tumor activities, the underlying mechanisms of how deguelin utilizes the tumor suppression effect through the metabolic pathways, were not fully understood [30]. Here, for the first time, we demonstrated that along with the down-regulation of HK2, the glycolysis in NSCLC was significantly inhibited after deguelin treatment.…”

Section: Discussionmentioning

confidence: 87%

Deguelin inhibits non-small cell lung cancer via down-regulating Hexokinases II-mediated glycolysis

Gao

et al. 2017

Oncotarget

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Hexokinases II (HK2) is a hub in the regulation of cancer cell glycolysis. Here we reported deguelin, a natural compound which has been studied in various tumor types, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via directly down-regulating of glycolysis. In NSCLC cell lines and primary NSCLC tissue, we found HK2 is overexpressed. Deguelin treatment markedly inhibited anchorage-dependent and independent growth of NSCLC cell lines. We revealed that deguelin exposure impaired glucose metabolism by inhibiting Akt-mediated Hexokinase II expression, overexpression of constitutively activated Akt1 substantially rescued deguelin-induced glycolysis suppression. Moreover, deguelin suppressed HK2 presence on mitochondrial outer membrane and induced apoptosis. The in vivo data indicated that deguelin prominently restrained tumor development in a xenograft mouse model. Thus, deguelin appears to be a promising new therapeutic agent for lung cancer and may be considered for further studies in other animal models and in clinical trials.

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“…deguelin (Figure 2F) and (−)-epigallocatechin-3-gallate (ECGT) (Figure 2G). Deguelin is a rotenoid molecule initially isolated from the African plant Mundulea sericea (Leguminosae) and later from other plants, which displayed potent and selective apoptotic and antiangiogenic effects on a variety of cancer cells (lung, prostate, gastric, and breast cancer) [122]. ECGT is the major polyphenol extracted from green tea, widely investigated for its antioxidant properties and for its possible effects in cancer prevention [123].…”

Section: Atra/arsenic Oxide Deguelin and (−)-Epigallocatechin-3-gallatementioning

confidence: 99%

Molecules that target nucleophosmin for cancer treatment: an update

et al. 2016

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Nucleophosmin is a highly and ubiquitously expressed protein, mainly localized in nucleoli but able to shuttle between nucleus and cytoplasm. Nucleophosmin plays crucial roles in ribosome maturation and export, centrosome duplication, cell cycle progression, histone assembly and response to a variety of stress stimuli. Much interest in this protein has arisen in the past ten years, since the discovery of heterozygous mutations in the terminal exon of the NPM1 gene, which are the most frequent genetic alteration in acute myeloid leukemia. Nucleophosmin is also frequently overexpressed in solid tumours and, in many cases, its overexpression correlates with mitotic index and metastatization. Therefore it is considered as a promising target for the treatment of both haematologic and solid malignancies. NPM1 targeting molecules may suppress different functions of the protein, interfere with its subcellular localization, with its oligomerization properties or drive its degradation. In the recent years, several such molecules have been described and here we review what is currently known about them, their interaction with nucleophosmin and the mechanistic basis of their toxicity. Collectively, these molecules exemplify a number of different strategies that can be adopted to target nucleophosmin and we summarize them at the end of the review.

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Deguelin, a novel anti-tumorigenic agent targeting apoptosis, cell cycle arrest and anti-angiogenesis for cancer chemoprevention

Cited by 73 publications

References 36 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 non-small cell lung cancer via down-regulating Hexokinases II-mediated glycolysis

Molecules that target nucleophosmin for cancer treatment: an update

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