crocin and Colorectal-Neoplasms

Colorectal cancer is one of the most common types of cancer in the world and the study of the role of nutrients in preventing or inhibiting the growth of this cancer is of interest to scientists. In this article, the synergistic effect of deuterium-depleted water(DDW) and crocin at specific concentrations on HT-29 cells was investigated. In this regard, HT-29 cells were grown in RPMI medium containing DDW, alone and in combination with crocin for 24, 48 and 72 h. Cell viability, cell cycle changes and antioxidant enzymes status were determined by MTT assay, flow cytometry and quantitative luminescence methods, respectively. The results of these analyses proved the cell growth inhibitory effect of deuterium alone and its synergistic effect in combination with crocin. The cell cycle analysis showed an increase in the number of cells in the G0 and G1 phases whereas there was a decrease in the number of cells in the S, G2 and M phases. The activities of superoxide dismutase and catalase enzymes also decreased compared to the control group that is a reason to increase Malonyl dialdehyde factor. The results suggested that a combination of DDW and crocin can open a new strategic approach in the prevention and treatment of colorectal cancer.

Topics: Colorectal Neoplasms; Deuterium; HT29 Cells; Humans; Water

As a chemoprevention agent, crocin effectively decreases the risk of human cancers, including colorectal cancer (CRC). However, the mechanism underlying the anti-cancer effects of crocin is not entirely explained. Considering that in this study, we investigated the crocin effect on miR-143/145 and related signaling pathways in CRC cells.. HCT-116 and HT-29 CRC cells were treated with different concentrations of crocin and then were subjected to MTT and qRT-PCR assays to investigate cell viability and miR-143/miR-145,. Our results showed that treating CRC cells with crocin decreases cell viability by upregulating miR-143/145 expression and reducing. This study suggests that crocin may inhibit CRC cell proliferation by modulating KRAS, REEB1, and AKT signaling pathways mediated through miR-143/145 upregulation.

Topics: Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins p21(ras); Transcription Factors

Curcumin, a polyphenol compound derived from the Curcuma longa L, and crocin, a hydrophilic carotenoid from Crocus Sativus Linnaeus, are traditionally used in food preparations in many countries and could act as chemopreventive compounds against several diseases, including cancer. In this study, the synergistic effect of curcumin and crocin was investigated for the first time on inducing apoptosis and suppressing colorectal cancer cells (SW-480 cell line).. MTT, Annexin V-FITC/PI, and DAPI staining tests were employed to evaluate cell viability and apoptosis induction, respectively. The combined effect of curcumin and crocin on the expression of genes involved in apoptosis and proliferation was quantified using real-time PCR. The combination therapy effect on cell cycle progression was also evaluated by flow cytometry. Based on the obtained results, curcumin and crocin treatment could cooperatively reduce cell viability and induce apoptosis in SW-480 cells by modulating the expression of Bax, Bcl-2, Caspase-3, Caspase-8, Caspase-9, Jak2, Stat3, and Akt1 genes. Besides, curcumin and crocin were able to synergistically increase the cell cycle arrest at the sub G1 phase, induce autophagy and decrease the clonogenic ability of SW-480 cells.. These results suggested that curcumin and crocin combination could be considered a more effective therapeutic strategy for inhibiting colorectal cancer.

Topics: Apoptosis; Carotenoids; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Curcumin; Humans

The high mortality rate of colorectal cancer (CRC) patients is directly associated with metastatic dissemination. However, therapeutic options specifically for metastasis are still limited. We previously identified Metastasis-Associated in Colon Cancer 1 (MACC1) as a major causal metastasis-inducing gene. Numerous studies confirmed its value as a biomarker for metastasis risk. We investigated the inhibitory impact of saffron on MACC1-induced cancer cell growth and motility. Saffron crudes restricted the proliferation and migration of MACC1-expressing CRC cells in a concentration- and MACC1-dependent manner. Saffron delays cell cycle progression at G2/M-phase and does not induce apoptosis. Rescue experiments showed that these effects are reversible. Analysis of active saffron compounds elucidated that crocin was the main compound that reproduced total saffron crudes effects. We showed the interaction of MACC1 with the cancer stem cell (CSC) marker DCLK1, which contributes to metastasis formation in different tumor entities. Saffron extracts reduced DCLK1 with crocin being responsible for this reduction. Saffron's anti-proliferative and anti-migratory effects in MACC1-expressing cells are mediated by crocin through DCLK1 down-regulation. This research is the first identification of saffron-based compounds restricting cancer cell proliferation and motility progression via the novel target MACC1.

Topics: Antineoplastic Agents; Carotenoids; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Crocus; Doublecortin-Like Kinases; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Plant Extracts; Protein Serine-Threonine Kinases; Trans-Activators

Colorectal cancer (CRC) is the third most common cause of cancer-related death, and hence there is a need for the identification of novel-agents to improve the efficacy of existing therapies. There is growing evidence for the antitumor activity of crocin, although its activity and molecular mechanisms in CRC remains to be elucidated. Here we explored the therapeutic application of crocin or its combination with 5-flurouracil in a mouse model of colitis-associated colon cancer. The antiproliferative activity of crocin was assessed in two-dimensional and three-dimensional cell-culture models. The migratory behaviors were determined, while the expression levels of several genes were assessed by quantitative reverse transcriptase polymerase chain reaction/Western blot analysis. We examined the anti-inflammatory properties of crocin by pathological evaluation and disease-activity index as well as oxidative or antioxidant markers: malondialdehyde (MDA) and total-thiols (T-SH) levels and superoxide dismutase (SOD) and catalase (CAT) activity. Crocin suppressed cell-growth and the invasive behavior of CRC cells through modulation of the Wnt-pathway and E-cadherin. Moreover, administration of crocin alone, or in combination with 5-FU dramatically reduced the tumor number and tumor size in both distal/mid-colon followed by reduction in disease-activity index. Crocin also suppressed the colonic inflammation induced by dextran-sulfate-sodium and notably recovered the increased levels of MDA, decreased thiol levels and activity of CAT levels. Crocin was able to ameliorate the severe inflammation with mucosal ulcers and high-grade dysplastic crypts as detected by inflammation score, crypt loss, pathological changes and histology scores. We demonstrated an antitumor activity of crocin in CRC and its potential role in improvement of inflammation with mucosal ulcers and high-grade dysplastic crypts, supporting the desireability of further investigations on the therapeutic potential of this approach in CRC.

Topics: Animals; Antioxidants; Carotenoids; Cell Proliferation; Colitis; Colorectal Neoplasms; Dextran Sulfate; Disease Models, Animal; Drug Synergism; Fluorouracil; Humans; Malondialdehyde; Mice; Oxidative Stress; Phosphatidylinositol 3-Kinases; Superoxide Dismutase; Wnt Signaling Pathway

Crocin, a bioactive molecule of saffron, inhibited proliferation of both HCT116 wild-type and HCT116 p53(-/-) cell lines at a concentration of 10 mM. Flow cytometric analysis of cell cycle distribution revealed that there was an accumulation of HCT116 wild-type cells in G1 (55.9%, 56.1%) compared to the control (30.4%) after 24 and 48 h of crocin treatment, respectively. However, crocin induced only mild G2 arrest in HCT116 p53(-/-) after 24 h. Crocin induced inefficient autophagy in HCT116 p53(-/-) cells, where crocin induced the formation of LC3-II, which was combined with a decrease in the protein levels of Beclin 1 and Atg7 and no clear p62 degradation. Autophagosome formation was not detected in HCT116 p53(-/-) after crocin treatment predicting a nonfunctional autophagosome formation. There was a significant increase of p62 after treating the cells with Bafilomycin A1 (Baf) and crocin compared to crocin exposure alone. Annexin V staining showed that Baf-pretreatment enhanced the induction of apoptosis in HCT116 wild-type cells. Baf-exposed HCT116 p53(-/-) cells did not, however, show any enhancement of apoptosis induction despite an increase in the DNA damage-sensor accumulation, γH2AX indicating that crocin induced an autophagy-independent classical programmed cell death.

Topics: Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Autophagy-Related Protein 7; Beclin-1; Carotenoids; Colorectal Neoplasms; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; HCT116 Cells; Humans; Membrane Proteins; Microtubule-Associated Proteins; RNA-Binding Proteins; Tumor Suppressor Protein p53; Ubiquitin-Activating Enzymes

To investigate the anti-proliferative effects of Crocus sativus extract and its major constituent, crocin, on three colorectal cancer cell lines (HCT-116, SW-480, and HT-29). The cell growth inhibition effect was compared to that of non-small cell lung cancer (NSCLC) cells. In addition, Crocus sativus' effect on non-cancer cells was evaluated.. Using high performance liquid chromatography (HPLC), the purity of crocin and the content of crocin extract were determined. Anti-proliferative effects of Crocus sativus extract and crocin on test cells was evaluated by MTS assay.. The purity of crocin was found to be 95.9% and the content of crocin in the extract was 22.9%. Significant concentration-related inhibition effects of the extract on all three colorectal cancer cell lines were observed (P<0.01). The proliferation was reduced most significantly in HCT-116 cells, to 45.5% at 1.0 mg/ml and to 6.8% at 3.0 mg/ml. Crocin at 1.0 mM, significantly reduced HCT-116, SW-480, and HT-29 cell proliferation to 2.8%, 52%, and 16.8%, respectively (P<0.01). Since 3.0 mg/ml Crocus sativus extract contained approximately 0.6 mM crocin, the observed effects suggest that crocin is a major responsible constituent in the extract. Significant anti-proliferative effects were also observed in non-small cell lung cancer cells. However, Crocus sativus extract did not significantly affect the growth of non-cancer young adult mouse colon cells.. Data from this study demonstrated that Crocus sativus extract and its major constituent, crocin, significantly inhibited the growth of colorectal cancer cells while not affecting normal cells. Crocus sativus extract should be investigated further as a viable option in the treatment of colorectal cancer.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Carotenoids; Cell Line, Tumor; Cell Proliferation; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Crocus; Drug Screening Assays, Antitumor; Humans; Intestinal Mucosa; Lung Neoplasms; Mice; Plant Extracts