Anticancer effects of crocetin in human esophageal squamous cell carcinoma KYSE-150 cells

Li, Sheng; Jiang, Sheng; Jiang, Wei; Zhou, Yue; Shen, Xing‐Xing; Luo, Tao; Ling-ping, Kong; Wang, Huaqiao

doi:10.3892/ol.2015.2869

Cited by 38 publications

(27 citation statements)

References 45 publications

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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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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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“…Increased incidence of esophageal cancer is due to obesity, smoking, consumption of hot beverages and red meat, increased alcohol intake and a decreased intake of fresh vegetables or fruit (22). The morbidity of squamous cell carcinoma is increasing in developing countries, particularly in China (23). According to the cancer stem cell theory, malignant tumors develop from a cancer stem cell, which has the capability of pluripotency and self-renewal (24).…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of ALDH1 combined with DAPI expression in patients with esophageal carcinoma

et al. 2017

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Abstract. Esophageal carcinoma is the most common type of tumor, with the incidence in China accounting for 50% of cases worldwide and the majority of patients not surviving due to tumor recurrence. According to the cancer stem cell theory, tumor development and recurrence is due to the excitation of a cancer stem cell. Aldehyde dehydrogenase 1 (ALDH1) is an appropriate marker for cancer stem cells and the present study aimed at determining the function of ALDH1 in human esophageal carcinoma. Indirect fluorescence antibody staining was used to investigate the association between the level of ALDH1 protein expression and clinicopathological parameters, including sex, age, vein invasion, degree of tumor cell differentiation and clinical stage. DAPI was used to stain the nuclei of tumor cells and exclude non-tumor cells. The results of the present study revealed that ALDH1 expression was associated with the level of tumor cell differentiation, tumor-node-metastasis stage and lymphatic invasion. In addition, increased expression of ALDH1 was identified in esophageal carcinoma tissues compared with in healthy esophageal tissues. Therefore, ALDH1 may be used as a parameter for the pathology of esophageal carcinoma.

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“…It also has anticancer effects. Growing evidence has indicated that crocetin can inhibit the proliferation of cancer cells in vitro [16,17] and regress the growth and metastases of tumors in vivo [16,18]. Moreover, the in vivo and in vitro showed that crocetin has no cytotoxic effects on normal cells [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

“…The cell proliferation was determined using MTT assay, as reported in our previous study [17]. To summarize briefly, cells were plated in 96 well plates at 6,000 cells/well.…”

Section: Mtt Assaymentioning

confidence: 99%

Multiple Signal Pathways Involved in Crocetin-Induced Apoptosis in KYSE-150 Cells

Shen

et al. 2019

Pharmacology

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Background: Crocetin is a carotenoid extracted from the traditional Chinese medical herb saffron. Previous studies have demonstrated that crocetin possesses anticancer properties that are effective against various cancers. As an extension of our earlier study, the present study explored the underlying mechanisms in crocetin’s anticancer effect on KYSE-150 cells. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), Mitogen-activated protein kinases (MAPK), and p53/p21 signal pathways play an important role in carcinogenesis, progression, and metastasis of carcinoma cells. Thus, we investigated crocetin’s effects on the PI3K/AKT, MAPK, and p53/p21 pathways in esophageal squamous carcinoma cell line KYSE-150 cells. Methods: KYSE-150 cells were treated with various concentrations of crocetin. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide assay, Annexin V/PI stain as well as Rh123 stain were used to evaluate the cell viability, apoptosis, and MMP. Western blot was used to detect the expression of PI3K, AKT, ERK1/2, p38, c-Jun NH-terminal kinase (JNK), P53, P21, Bcl-2, Bax, and cleaved caspase-3, which were associated with cell proliferation and apoptosis. Results: Our results showed that crocetin significantly inhibited the proliferation of KYSE-150 cells in a dose- and time-dependent manner. Crocetin also markedly induced cell apoptosis. Furthermore, we have found that crocetin not only inhibited the activation of PI3K/AKT, extracellular signal–regulated kinase-1/2 (ERK1/2), and p38 but also upregulated the p53/p21 level. These regulations ultimately triggered the mitochondrial-mediated apoptosis pathway with an eventual disruption of MMP, increased levels of Bax and cleaved caspase-3, and decreased levels of Bcl-2. Conclusions: These findings suggested that crocetin interfered with multiple signal pathways in KYSE-150 cells. Therefore, this study suggested that crocetin could potentially be used as a therapeutic candidate for the treatment of esophageal cancer.

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Anticancer effects of crocetin in human esophageal squamous cell carcinoma KYSE-150 cells

Cited by 38 publications

References 45 publications

Crocetin Activates Foxp3 Through TIPE2 in Asthma-Associated Treg Cells

Crocetin Activates Foxp3 Through TIPE2 in Asthma-Associated Treg Cells

Clinical significance of ALDH1 combined with DAPI expression in patients with esophageal carcinoma

Multiple Signal Pathways Involved in Crocetin-Induced Apoptosis in KYSE-150 Cells

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