Crocin inhibits proliferation and induces apoptosis through suppressing MYCN expression in retinoblastoma

Deng, Liya; Li, Jincun; Lü, Shiyou; Su, Yan

doi:10.1002/jbt.22292

Cited by 17 publications

(9 citation statements)

References 36 publications

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“…Immunoblot analyses of ADSCs and iSCs after 7 and 19 days of induction were performed with precast gradient gels using standard methods (Deng et al 2019). Briefly, cells were lysed in radioimmunoprecipitation assay (RIPA) buffer and normalized using a BCA protein assay kit (Ther-moFisher Scientific, Carlsbad, CA, USA).…”

Section: Detecting the Effect Of Different Induction Times On Proliferation Senescence And Apoptosis Of Iscsmentioning

confidence: 99%

Effect of Induction Time on the Proliferation and Differentiation of Induced Schwann-Like Cells from Adipose-Derived Stem Cells

Wong

Liu

et al. 2020

Cell Mol Neurobiol

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To compare how different induction time takes effect on the proliferation and secretion ability of adipose-derived stem cell (ADSC)-induced Schwann-like cells (iSCs), ADSCs were isolated from healthy adult female rats. Flow cytometry (FCM) was performed to detect the ADSC-positive markers CD29, CD44, and CD90 and the negative marker CD45. iSC induction medium was used to culture the ADSCs. S-100, GFAP, MBP, and P75 were detected by immunofluorescence staining to identify iSC differentiation. Cell morphological changes were observed by an inverted microscope after induction. An MTS assay was used to evaluate the cell proliferation ability. Western blot analyses of caspase-3/cleaved caspase-3 and FCM were applied to assess cell apoptosis. Co-culture system of PC12 and ADSCs or iSCs was established to analyse the biological function of iSCs. Among the examined proteins, S-100, GFAP, MBP, and P75 were expressed in iSCs. After day 7, the cell proliferation rate was significantly lower than that before induction, and on day 19, the proliferation rate of iSCs was lower than 50% of the proliferation rate before induction (OD value = 0.016 ± 0.003 vs. 0.400 ± 0.004, p < 0.01). Starting from day 19, P21, P53, Apoj, S100, Gdnf, and Mbp all consistently showed a trend toward increased expression. Secretion of NGF, MBP, and BDNF was more enhanced at 19 days than that at 7 days. In co-culture system, the induction effect of iSCs was more pronounced at 19 days than that at 7 days, and the difference was statistically significant (55.40 ± 4.50 μm vs 37.15 ± 3.75 μm, p < 0.01). In conclusion, the proliferation ability of ADSC-derived iSCs was negatively correlated with the induction time, while the expression of SC marker proteins was positively correlated. Therefore, iSCs are suitable for use at 19 days after induction.

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Section: Detecting the Effect Of Different Induction Times On Proliferation Senescence And Apoptosis Of Iscsmentioning

confidence: 99%

Effect of Induction Time on the Proliferation and Differentiation of Induced Schwann-Like Cells from Adipose-Derived Stem Cells

Wong

Liu

et al. 2020

Cell Mol Neurobiol

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“…In recent years, many authors studied the effects of different natural compounds on GBM [22]; among these, SE raised great interest. Crocetin is the major active product of SE and has an elevated capacity to counteract the survival and progression of different cancer types [24,[26][27][28]. However, the effects of crocetin on GBM are poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma

Colapietro

Mancini

Vitale

et al. 2020

IJMS

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Over recent years, many authors discussed the effects of different natural compounds on glioblastoma (GBM). Due to its capacity to impair survival and progression of different cancer types, saffron extract (SE), named crocetin (CCT), is particularly noteworthy. In this work, we elucidated the antitumor properties of crocetin in glioma in vivo and in vitro models for the first time. The in vitro results showed that the four tumor cell lines observed in this study (U251, U87, U138, and U373), which were treated with increasing doses of crocetin, showed antiproliferative and pro-differentiative effects as demonstrated by a significant reduction in the number of viable cells, deep changes in cell morphology, and the modulation of mesenchymal and neuronal markers. Indeed, crocetin decreased the expression of Cluster of Differentiation CD44, CD90, CXCR4, and OCT3/4 mesenchymal markers, but increased the expression of βIII-Tubulin and neurofilaments (NFH) neuronal linage-related markers. Epigenetic mechanisms may modulate these changes, since Histone Deacetylase, HDAC1 and HDAC3 were downmodulated in U251 and U87 cells, whereas HDAC1 expression was downmodulated in U138 and U373 cells. Western blotting analyses of Fatty Acid Synthase, FASN, and CD44 resulted in effective inhibition of these markers after CCT treatment, which was associated with important activation of the apoptosis program and reduced glioma cell movement and wound repair. The in vivo studies aligned with the results obtained in vitro. Indeed, crocetin was demonstrated to inhibit the growth of U251 and U87 cells that were subcutaneously injected into animal models. In particular, the Tumor To Progression or TTP values and Kaplan–Meier curves indicated that crocetin had more major effects than radiotherapy alone, but similar effects to temozolomide (TMZ). An intra-brain cell inoculation of a small number of luciferase-transfected U251 cells provided a model that was able to recapitulate recurrence after surgical tumor removal. The results obtained from the orthotopic intra-brain model indicated that CCT treatment increased the disease-free survival (DFS) and overall survival (OS) rates, inducing a delay in appearance of a detectable bioluminescent lesion. CCT showed greater efficacy than Radio Therapy (RT) but comparable efficacy to temozolomide in xenograft models. Therefore, we aimed to continue the study of crocetin’s effects in glioma disease, focusing our attention on the radiosensitizing properties of the natural compound and highlighting the ways in which this was realized.

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“…Crocin is a natural carotenoid extracted from saffron that is known to have various biological activity including renoprotective (10), anti-oxidant (11), anti-depressant (12) and anti-inflammatory (13) effects. Further, a growing number of papers have confirmed that Crocin also inhibits the progression of multiple cancers (14)(15)(16). Zhou et al reported that Crocin inhibited migration, invasion, and epithelial-mesenchymal transition (EMT) in GC cells (17).…”

Section: Original Articlementioning

confidence: 99%

Crocin reverses 1-methyl-3-nitroso-1-nitroguanidine (MNNG)-induced malignant transformation in GES-1 cells through the Nrf2/Hippo signaling pathway

Wu¹,

Hui²

2020

J Gastrointest Oncol

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Background: Crocin, an active constituent of saffron, has anticancer activity. In this study, we investigated the relationship of Crocin with human gastric epithelial cells induced by 1-methyl-3-nitroso-1-nitroguanidine (MNNG), and explored the underlying mechanism. Methods: In vivo, the animal growth and atypical hyperplasia were observed in Sprague-Dawley rats. A cell model was established by treating the human gastric mucosa epithelial cell line GES-1 with MNNG.The effects of Crocin on proliferation, cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT) in GES-1 cells were analyzed using Cell Counting Kit-8, colony formation, flow cytometry, and Transwell assay, respectively. Western blot was used to explore the potential mechanism.. Results: The gastric mucosa of animal model deteriorated obviously, the weight growth rate slowed down, and the atypical hyperplasia of gastric mucosa increased. The GES-1 cells had characteristics of malignant cells such as proliferation, apoptosis, and metastasis ability. It was found that Crocin suppressed the cell proliferation, increased apoptosis, and blocked the cycle arrest in G0/G1 phase simultaneously. Furthermore, Crocin negatively regulated the invasion ability of MNNG-treated GES-1 cells and EMT process. Crocin also increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), decreased TAZ in MNNG-treated GES-1 cells. Interestingly, Crocin regulated the expression of TAZ and yes-associated protein (YAP) by increasing Nrf2 level, as well as their upstream targets, mercaptopyruvate sulfurtransferase (MST) and large tumor suppressor (LATS). Conclusions: Crocin protected against MNNG-induced malignant transformation through the Nrf2/ Hippo signaling pathway, which might be a drug candidate for clinical gastric cancer management.

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Crocin inhibits proliferation and induces apoptosis through suppressing MYCN expression in retinoblastoma

Cited by 17 publications

References 36 publications

Effect of Induction Time on the Proliferation and Differentiation of Induced Schwann-Like Cells from Adipose-Derived Stem Cells

Effect of Induction Time on the Proliferation and Differentiation of Induced Schwann-Like Cells from Adipose-Derived Stem Cells

Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma

Crocin reverses 1-methyl-3-nitroso-1-nitroguanidine (MNNG)-induced malignant transformation in GES-1 cells through the Nrf2/Hippo signaling pathway

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