Nigericin selectively targets cancer stem cells in nasopharyngeal carcinoma

Deng, Chang‐Mi; Lv, Yi; Wu, Man; Feng, Fu Tuo; Hu, Wen; Chen, Li Zhen; Feng, Qi Sheng; Bei, Jin Xin; Zeng, Yi Xin

doi:10.1016/j.biocel.2013.06.023

Cited by 47 publications

(33 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Phenolic compounds resveratrol suppresses stemness of NPC CSCs[31], and the epithelial mesenchymal transition (EMT) which is considered as one of the origin of CSCs[32]. Nigericin, an antibiotic derived from Streptomyces hygroscopicus targets NPC CSC both in vitro and in vivo [33]. Recently, a specific Skp2 inhibitor is identified using high-throughput screening from large and diverse chemical libraries.…”

Section: Discussionmentioning

confidence: 99%

E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma

et al. 2014

View full text Add to dashboard Cite

Nasopharyngeal carcinoma (NPC) is one of the severe head and neck carcinomas, which is rare in west countries but has high incidence in Southern Asia especially South China. Although NPC is relatively sensitive to radiotherapy, the prognosis of patients is poor due to the advanced stage at the time of diagnosis. Therefore, it is important to understand the mechanisms involved in tumorigenesis and develop early diagnostic techniques. S-phase kinase associated protein 2 (Skp2) is overexpressed in several human cancers and associates with poor prognosis. However, its function in NPC has not been fully addressed. In this study we found Skp2 was highly expressed in NPC specimen and correlated with poor prognosis. We generated Skp2 knockdown cells to further delineate its role in NPC development. Knockdown of Skp2 partially reduced cell proliferation, promoted cellular senescence, and decreased the population of stem cell like aldehyde dehydrogenase1 positive cells as well as their self-renewal ability. Our study not only interprets the predictive role of Skp2 in the poor prognosis of NPC patients, but also reveals that Skp2 regulates the NPC cancer stem cell maintenance, which shed lights on the target therapy and early diagnosis of NPC in clinical application.

show abstract

Section: Discussionmentioning

confidence: 99%

E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Residual foci detected by clinical or imaging methods may be composed of cancer parenchyma-like cancer stem cells and delayed reproductive-dead cells, as well as other cell types including interstitial tissue-like fibrosis and mononuclear cells [3]. While reproductive-dead cells will disappear within several months, radio-resistant cancer stem cells are thought to be the root cause of relapse and metastasis [4], and the radio-response of the interstitial tissue is also associated with recurrence [3]. Given these possibilities, clinicians need to decide whether or not to increase the local dosage or provide timely additional adjuvant chemotherapy for patients with radiographically-visible residual tumors at the end of radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

A retrospective study of the prognostic value of MRI-derived residual tumors at the end of intensity-modulated radiotherapy in 358 patients with locally-advanced nasopharyngeal carcinoma

Zhou

Shen

et al. 2015

Radiat Oncol

View full text Add to dashboard Cite

ObjectiveTo retrospectively analyze the prognostic value of magnetic resonance imaging (MRI)-derived residual tumors after intensity-modulated radiation therapy (IMRT) in the patients with locally-advanced nasopharyngeal carcinoma.MethodsA total of 358 patients with locally-advanced nasopharyngeal carcinoma who received IMRT were classified as having residual tumors or no residual tumor based on MRI at the end of radiotherapy. The χ2 test, log-rank test, Cox proportional hazards regression model and Kaplan-Meir survival curves were used to investigate the relationship of clinicopathological features and residual tumors and to assess the prognostic value of residual tumors.ResultsThe 3-year overall survival (OS) rate was 73% in the residual tumor group and 90% in the no residual tumor group (HR 2.15, 95% CI 1.21-3.82,, P = 0.007); 3-year local relapse-free survival (LRFS) was 89% in the residual tumor group and 97% in the no residual tumor group (HR 4.46, 95% CI 1.61-12.38, P = 0.002); 3-year disease free survival (DFS) was 67% in the residual tumor group and 82% in the no residual tumor group (HR 2.21, 95% CI 1.40-3.48, P = 0.001). A high prescribed radiation dose (>73.92 Gy) did not increase the percentage volume of the GTVnx receiving 95% of the prescribed dose (GTVnx V95%) or improve any survival outcome.ConclusionThe presence of a residual tumor after IMRT was a significant negative independent prognostic factor for OS, LRFS and DFS. Although IMRT have improved the distribution of radiotherapy doses into the tumors, residual tumors detected by MRI after IMRT are still associated with poor prognosis in patients with advanced nasopharyngeal carcinoma.

show abstract

“…Western blotting was performed as previously described (27). Briefly, cells were lysed in RIPA lysis buffer on ice, and the clarified lysates were resolved by SDS-PAGE and transferred to polyvinylidenedifluoride membranes for Western blotting using ECL detection reagents (Beyotime).…”

Section: Western Blot Analysismentioning

confidence: 99%

Unconjugated Bilirubin Is a Novel Prognostic Biomarker for Nasopharyngeal Carcinoma and Inhibits Its Metastasis via Antioxidation Activity

Deng

et al. 2016

Cancer Prevention Research

Self Cite

View full text Add to dashboard Cite

Distant metastasis is the most common cause of treatment failure and mortality in nasopharyngeal carcinoma (NPC) patients. Thus, it is important to understand the mechanism of NPC metastasis and identify reliable prognostic factors. In this study, we investigated the prognostic value of unconjugated bilirubin (UCB), which was previously considered a byproduct of heme catabolism, in NPC patients and examined the effects of UCB on NPC metastasis. The receiver operating characteristic analysis-generated UCB cutoff point for DMFS was 9.7 mmol/L. We found that higher UCB levels were significantly associated with favorable distant metastasis-free survival (DMFS, 93.3% vs. 84.2%, P < 0.001) in NPC patients and was an independent predictor for DMFS (HR, 0.416; 95% confidence interval, 0.280-0.618; P < 0.001). We next found that UCB treatment impaired the invasion capability of NPC cells and potently inhibited lung metastasis of NPC cells in nude mice. Further investigation showed that UCB inhibited reactive oxygen species production, which is involved in the repression of ERK1/2 activation and matrix metalloproteinase-2 (MMP-2) expression. Moreover, lower levels of ERK1/2 phosphorylation and MMP-2 expression were observed in the NPC lung metastases of nude mice administered UCB. Taken together, our results indicate that UCB is a significantly favorable factor for DMFS in NPC patients and may play an important role in NPC chemoprevention. Cancer Prev Res; 9(2);

show abstract

Nigericin selectively targets cancer stem cells in nasopharyngeal carcinoma

Cited by 47 publications

References 39 publications

E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma

E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma

A retrospective study of the prognostic value of MRI-derived residual tumors at the end of intensity-modulated radiotherapy in 358 patients with locally-advanced nasopharyngeal carcinoma

Unconjugated Bilirubin Is a Novel Prognostic Biomarker for Nasopharyngeal Carcinoma and Inhibits Its Metastasis via Antioxidation Activity

Contact Info

Product

Resources

About