Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines

Kim, Se Hyeuk; Lee, Jung Min; Kim, Sun Chang; Park, Chan Bae; Lee, Pyung Cheon

doi:10.1139/bcb-2013-0091

Cited by 70 publications

(44 citation statements)

References 22 publications

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“…This level increased by crocin pretreatment. Our findings are in agreement with an in vitro study which showed that crocin increases the expression and activity of Nrf2 in Hela cells [58]. Recently, in one study, authors have shown that crocin pretreatment protects the gastric mucosa against IR-induced injury through upregulating the mRNA expression and activity of antioxidant enzymes in rats [59].…”

Section: Discussionsupporting

confidence: 92%

The Hepatoprotective and MicroRNAs Downregulatory Effects of Crocin Following Hepatic Ischemia‐Reperfusion Injury in Rats

Akbari

Mard

Dianat

et al. 2017

Oxidative Medicine and Cellular Longevity

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Background. Liver ischemia-reperfusion (IR) injury is one of the chief etiologies of tissue damage during liver transplantation, hypovolemic shock, and so forth. This study aimed to evaluate hepatoprotective effect of crocin on IR injury and on microRNAs (miR-122 and miR-34a) expression. Materials and Methods. 32 rats were randomly divided into four groups: sham, IR, crocin pretreatment (Cr), and crocin pretreatment + IR (Cr + IR) groups. In sham and Cr groups, animals were given normal saline (N/S) and Cr (200 mg/Kg) for 7 consecutive days, respectively, and laparotomy without inducing IR was done. In IR and Cr + IR groups, N/S and Cr were given for 7 consecutive days and rats underwent a partial (70%) ischemia for 45 min/reperfusion for 60 min. Blood and tissue samples were taken for biochemical, molecular, and histopathological examinations. Results. The results showed decreased levels of antioxidants activity and increased levels of liver enzymes improved by crocin. The expression of miR-122, miR-34a, and p53 decreased, while Nrf2 increased by crocin. Crocin ameliorated histopathological changes. Conclusion. The results demonstrated that crocin protected the liver against IR injury through increasing the activity of antioxidant enzymes, improving serum levels of liver enzymes, downregulating miR-122, miR-34a, and p53, and upregulating Nrf2 expression.

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Section: Discussionsupporting

confidence: 92%

The Hepatoprotective and MicroRNAs Downregulatory Effects of Crocin Following Hepatic Ischemia‐Reperfusion Injury in Rats

Akbari

Mard

Dianat

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…In order to explore potential of this compound to treat this kind of tumor in more detail, we reported results regarding in vivo and in vitro models of glioma treated with crocetin. Several authors demonstrated the in vitro antiproliferative action of crocetin in different kinds of tumor cells [29][30][31][32]. In order to evaluate the antiproliferative effect of crocetin on GBM cells, four tumor lines (U251, U87, U138, and U373) were treated with 250 µM and 500 µM of crocetin and counted after 72 h of incubation.…”

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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“…Saffron is a Chinese traditional herb, and Crocetin is the major constituent of saffron, which has recently found to have multiple pharmacological effects including anticancer [15][16][17]. However, the effects of Crocetin on asthma as well as the underlying mechanisms have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Crocetin Activates Foxp3 Through TIPE2 in Asthma-Associated Treg Cells

Ding

Zhang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Regulatory T cells (Treg) are critical regulators of asthma. Crocetin is isolated from Chinese herb saffron and is a natural carotenoid dicarboxylic acid with anti-inflammatory potential. However, the effects of Crocetin on asthma as well as the underlying mechanisms have not been studied. Methods: We used Crocetin to treat mice with established ovalbumin (OVA)-induced asthma. We purified CD4+CD25+ Treg cells by flow cytometry and analyzed the levels of two immunoregulatory proteins Foxp3 and tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) in Treg cells. We depleted either Foxp3 or TIPE2 in mouse lung through lentivirus-mediated delivery of shRNA, and analyzed their effects on severity of asthma and Treg cells after Crocetin treatment. Results: Crocetin treatment significantly reduced the severity of an ovalbumin (OVA)-induced asthma in mice. Moreover, Crocetin significantly increased the levels of TIPE2 and Foxp3 in Treg cells and the number of Treg cells. Depletion of Foxp3 abolished the increased in Treg cells, and the effects of Crocetin on the severity of asthma, without affecting TIPE2 levels in Treg cells. On the other hand, depletion of TIPE2 abolished both the increased in Treg cells and the effects of Crocetin on the severity of asthma, through suppressing Foxp3. Conclusion: Crocetin may activate Foxp3 through TIPE2 in asthma-associated Treg cells to mitigate the severity of asthma.

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Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines

Cited by 70 publications

References 22 publications

The Hepatoprotective and MicroRNAs Downregulatory Effects of Crocin Following Hepatic Ischemia‐Reperfusion Injury in Rats

The Hepatoprotective and MicroRNAs Downregulatory Effects of Crocin Following Hepatic Ischemia‐Reperfusion Injury in Rats

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

Crocetin Activates Foxp3 Through TIPE2 in Asthma-Associated Treg Cells

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