Crocin has pharmacological effects against the pathological behavior of colon cancer cells by interacting with the STAT3 signaling pathway

Wang, Jun; Ke, Yupei; Shu, Tao

doi:10.3892/etm.2019.8329

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…The significant changes compared with vehicle-treated (0 mg/kg of crocin) mice marked as^p value. (Wang et al, 2020) and 3 mM (24 h IC 50 ) in CT-26 cells (Amerizadeh et al, 2018). In SW480 cells, our data is consistent with previous research (Li et al, 2012).…”

Section: Discussionsupporting

confidence: 92%

“…This study has some limitations. According to previous studies, crocin reduced the cell viability at different concentrations in different cells, such as 271.18 μM (48 h IC 50 ) in HCT116 cells ( Wang et al, 2020 ) and 3 mM (24 h IC 50 ) in CT-26 cells ( Amerizadeh et al, 2018 ). In SW480 cells, our data is consistent with previous research ( Li et al, 2012 ).…”

Section: Discussionmentioning

confidence: 87%

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The Protection of Crocin Against Ulcerative Colitis and Colorectal Cancer via Suppression of NF-κB-Mediated Inflammation

Teng

Hao

et al. 2021

Front. Pharmacol.

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Background: In China, the incidence of ulcerative colitis (UC) is increasing every year, but the etiology of UC remains unclear. UC is known to increase the risk of colorectal cancer (CRC). The aim of this study was to investigate the protective effects of crocin against UC and CRC in mouse models.Methods: Crocin was used to treat the dextran sodium sulfate (DSS)-induced UC mice for 3 weeks, and ApcMinC/Gpt mice with colorectal cancer for 8 weeks. Proteomics screening was used to detect changes in the protein profiles of colon tissues of UC mice. Enzyme-linked immunosorbent assays and western blot were used to verify these changes.Results: Crocin strongly reduced the disease activity index scores of UC mice, and improved the pathological symptoms of the colonic epithelium. The anti-inflammatory effects of crocin were indicated by its regulation of the activity of various cytokines, such as interleukins, via the modulation of nuclear factor kappa-B (NF-κB) signaling. Crocin significantly suppressed tumor growth in ApcMinC/Gpt mice and ameliorated pathological alterations in the colon and liver, but had no effects on spleen and kidney. Additionally, crocin significantly decreased the concentrations of interleukins and tumor necrosis factor-α in the sera and colon tissues, suggesting its anti-inflammatory effects related to NF-κB signaling. Finally, 12-h incubation of SW480 cells with crocin caused cell cycle arrest, enhanced the apoptotic rate, promoted the dissipation of mitochondrial membrane potential, and the over-accumulation of reactive oxygen species. From the theoretical analyses, phosphorylated residues on S536 may enhance the protein-protein interactions which may influence the conformational changes in the secondary structure of NF-κB.Conclusion: The protective effects of crocin on UC and CRC were due to its suppression of NF-κB-mediated inflammation.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 87%

The Protection of Crocin Against Ulcerative Colitis and Colorectal Cancer via Suppression of NF-κB-Mediated Inflammation

Teng

Hao

et al. 2021

Front. Pharmacol.

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“…On treatment with safranal and crocin, the cells exhibited a dose-dependent cell viability inhibition pattern, similar to saffron (Figures 3 and 4). Safranal and crocin dose ranges in our study are close to the effective doses published for other cancers [9,18,19]. Malaekeh-Nikouei et al have reported safranal's effective dose range to be much higher for other cells suggesting that HCT116 cells have a higher susceptibility [20].…”

Section: Discussionsupporting

confidence: 86%

“…The results of crocin treatment are also consistent with the previous findings where the crocin treatment has inhibited invasion of different cell lines including HUVEC (human umbilical vein endothelial cells), AGS and HGS-27 (gastric cancer cells), and MG63 (osteosarcoma) [22,23]. Interestingly, Wang et al reported crocin's inability to inhibit the invasion of HCT116 cells, at 271.18 µM, but comparing it with the present findings suggests that a higher dose is required to inhibit invasiveness (Figure 5) [19]. In patients with CRC, recurrence and metastasis are the most common causes of cancer-related death.…”

Section: Discussionsupporting

confidence: 77%

Saffron and Its Major Ingredients’ Effect on Colon Cancer Cells with Mismatch Repair Deficiency and Microsatellite Instability

et al. 2021

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Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. One of its subtypes is associated with defective mismatch repair (dMMR) genes. Saffron has many potentially protective roles against colon malignancy. However, these roles in the context of dMMR tumors have not been explored. In this study, we aimed to investigate the effects of saffron and its constituents in CRC cell lines with dMMR. Methods: Saffron crude extracts and specific compounds (safranal and crocin) were used in the human colorectal cancer cell lines HCT116, HCT116+3 (inserted MLH1), HCT116+5 (inserted MSH3), and HCT116+3+5 (inserted MLH1 and MSH3). CDC25b, p-H2AX, TPDP1, and GAPDH were analyzed by Western blot. Proliferation and cytotoxicity were analyzed by MTT. The scratch wound assay was also performed. Results: Saffron crude extracts restricted (up to 70%) the proliferation in colon cells with deficient MMR (HCT116) compared to proficient MMR. The wound healing assay indicates that deficient MMR cells are doing better (up to 90%) than proficient MMR cells when treated with saffron. CDC25b and TDP1 downregulated (up to 20-fold) in proficient MMR cells compared to deficient MMR cells, while p.H2AX was significantly upregulated in both cell types, particularly at >10 mg/mL saffron in a concentration-dependent manner. The reduction in cellular proliferation was accompanied with upregulation of caspase 3 and 7. The major active saffron compounds, safranal and crocin reproduced most of the saffron crude extracts’ effects. Conclusions: Saffron’s anti-proliferative effect is significant in cells with deficient MMR. This novel effect may have therapeutic implications and benefits for MSI CRC patients who are generally not recommended for the 5-fluorouracil-based treatment.

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“…Previous research suggested that crocin promoted the phosphorylation of STAT3 in the colon cancer cells. [ 39,40 ] Previous studies have revealed a similar pattern of inhibition of breast cancer cells in Riccardin D induced apoptosis. [ 41 ] Altogether, these results suggested that following NF‐κB inhibition, crocin may induce apoptosis via modulating the MAPK‐regulated apoptotic signaling pathway.…”

Section: Discussionmentioning

confidence: 84%

Crocin treatment promotes the oxidative stress and apoptosis in human thyroid cancer cells FTC‐133 through the inhibition of STAT/JAK signaling pathway

Zhang

Zhu

Mohan³

et al. 2020

J Biochem & Molecular Tox

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Thyroid cancer is the most frequent endocrine malignancy, which accounts for nearly 1% of all the cancer worldwide. Crocin has a diverse biological function, such as anti‐cancer, anti‐inflammatory and antioxidant functions, specifically in the respiratory related diseases. Using in vitro techniques, this work was intended to illuminate the anti‐cancer effect of crocin in follicular thyroid carcinoma (FTC) (FT 133 cells), and the potential molecular mechanism convoluted. The outcome of the present work showed that crocin was able to prevent the proliferation and triggering the apoptosis in a dose‐dependent mode, of FTC‐133 cells by methyl thiazolyldiphenyl‐tetrazolium bromide and staining assay (acridine orange/propiduim iodide [PI], 4′,6‐diamidino‐2‐phenylindole, and PI dye). Crocin did not show toxicity to the normal thyroid (PCCL3) cells. Crocin‐induced reactive oxygen species, mitochondrial membrane potential activity, caspase‐8 and ‐9, lipid peroxidation (thiobarbituric acid reactive substances) activity while suppressing antioxidant activity (superoxide dismutase, catalase, and glutathione) in FTC‐133 cells. In addition, crocin was also participated in a halting of the proteins related to cell cycle, cyclin D1, and pro‐apoptotic proteins; Bax and caspase‐3 expression, together with the elevation of anti‐apoptotic factor Bcl‐2. Further, crocin have a dual inhibition of two major pathways, nuclear factor‐κB, extracellular signal‐regulated kinase, and janus kinase‐signal transducer and activator of transcription signaling pathways. In conclusion, crocin can inhibit follicular thyroid carcinoma proliferation and promote cell apoptosis.

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Crocin has pharmacological effects against the pathological behavior of colon cancer cells by interacting with the STAT3 signaling pathway

Cited by 12 publications

References 30 publications

The Protection of Crocin Against Ulcerative Colitis and Colorectal Cancer via Suppression of NF-κB-Mediated Inflammation

The Protection of Crocin Against Ulcerative Colitis and Colorectal Cancer via Suppression of NF-κB-Mediated Inflammation

Saffron and Its Major Ingredients’ Effect on Colon Cancer Cells with Mismatch Repair Deficiency and Microsatellite Instability

Crocin treatment promotes the oxidative stress and apoptosis in human thyroid cancer cells FTC‐133 through the inhibition of STAT/JAK signaling pathway

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