الهام قدوسی دهنوی

Colorectal cancer is a clinically heterogeneous disease resulting from metabolome pattern alterations of many metabolites and their genetic factor interactions in man. Chemotherapy in colorectal cancer is generally followed by multiple side effects, including drug resistance; It is well established that herbal medicines are gaining worldwide interest in treating many cancers. Vitexin is an apigenin flavone glycoside present in hawthorn has exhibited therapeutic properties. This study was performed to assess the antitumor properties of Vitexin on the expression of p53, KRAS, and APC genes and the metabolome profile alterations associated with these genetic modifications.

Experimental: 

Cells were treated with different concentrations of Vitexin, and toxicity and cell growth inhibition were ascertained in vitro using the MTT assay method. Cells were treated with Vitexin, and gene expression was determined. Following metabolome 1HNMR spectroscopy with 1D NOESY protocol and the resulting spectra scrutinized to classify differentiated metabolites and their biochemical pathways. Integrative systems biology analysis software examined the metabolites and the genes, and the main pathways modulated by gene expression were identified.

Our finding revealed that a 50% inhibitory concentration for Vitexin was 16.32 μM, while the relative expression of tumor suppressor genes APC and p53 in treated cells enhanced and the expression of the KRAS oncogene gene decreased significantly compared to the control group. The crucial changes in convergent metabolic phenotype with genes were identified in this investigation.

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Our findings revealed that Vitexin exhibits antitumor properties by targeting a specific biochemical pathway in the cell's metabolome profile due to changes in genes involved in colon cancer.

In traditional medicine, Zizyphus jujuba (jujube) has been used due to its medicinal properties and various physiological functions such as antioxidant, anticancer and anti-inflammatory properties. This study was conducted to study anti-cancer and apoptotic effects of essential oil from Zizyphus jujuba seeds and to evaluate the effect of essential oils on p53, APC and KRAS genes expression in HT-29 colorectal cell line.

In this study, the essential oil of jujube seeds collected from orchards in Isfahan was prepared by Clevenger apparatus and then analyzed by GC-MS. The effects of toxicity and cell viability were determined using Trypan Blue, MTT and clonogenic methods. DNA fragmentation and apoptosis techniques were used to evaluate the mechanism of the effects of essential oil on cell death by flow cytometry. Finally, Real-time PCR was used to evaluate the expression of p53, APC and KRAS genes and their role in induction of apoptosis.

Essential oil of Zizyphus jujuba seeds reduced the viability of cells by concentration and time-dependent manner as compared to the control group. The essential oil also induced apoptosis by increasing gene expression p53 and suppressing gene expression KRAS.

The present results indicated that essential oil of Zizyphus jujuba seeds induces apoptosis by targeting genes involved in colon carcinogenesis. However, further investigations on signaling pathways are needed to fully confirm the results of this study.

Fermented beverage, traditionally the result of the fermentation of sweet tea by Kombucha fungus, has beneficial effects in the treatment of many diseases, especially cancer. The present study is aimed at assessing the effect of different fractions of Kombucha tea on proliferation and apoptosis on colon cancer cell line HT-29. In the present experimental study, the survival rate and cell proliferation of Kumbucha tea solvent fractions including chloroform, ethyl acetate, butanol, hexane, and the final aqueous phase at concentrations of 0-900 μg/ ml were investigated by MTT and clonogenic assay. The rate of apoptosis induction was assessed by DNA fragmentation assay and flowcytometry. The aqueous and butanol fractions had no cytotoxic effects. After 24 hours, the IC50 for ethyl acetate, chloroform, and hexane was determined 213/49±1/63, 296/70±2/11 and 563/2±83/29 μg/ml, respectively. The results revealed that inhibition of cell growth was dose-dependent. The concentration of IC50 in these fractions caused the DNA to fragment. Apoptosis analysis by flowcytometry with these concentrations showed that the ethyl acetate component caused apoptosis while the death caused by IC50 concentrations of chloroform and hexane fractions was more than necrosis. The dose-dependent ethyl acetate fraction of Kambucha tea induced cell death through the apoptotic pathway and it was observed to be responsible for the anti-apoptotic and anti-proliferative properties. It seems to be a good candidate to prevent the proliferation of colorectal cancer cells.

Migration and invasion features, which were associated with inflammatory response, play a vital role in the pathogenesis of osteoarthritis. Metalloproteinases (MMPs) as one of the most important catabolic bio-markers play a critical role in THP-1 invasion and migration induced by lipopolysaccharides (LPS). The aim of this study was to investigate the anti-invasive and anti-migratory properties of Zizyphus jujuba seed essential oil by inhibiting metalloproteinase 1, 2, 3, and 9, which are expressed during the development of osteoarthritis. The seeds of Z. jujuba were collected from Isfahan. The seeds were separated and the essence was extracted in the Center of Genetic Resources of Iran. The effect of Zizyphus jujuba seed essential oil on cell viability, migration, and invasion of THP-1 cells was analyzed using MTT assay and transwell chambers assay, respectively. The expression of MMP-1, 2, 3, and 9 genes was evaluated by Real-time PCR, protein expression with Western blotting and ELISA, and the activity of MMP-2 and MMP-9 was investigated by gelatin-zymography. Zizyphus jujuba seed essential oil (50 μg/ml) could remarkably suppress the migratory and invasive capacity of THP-1cells stimulated with LPS compared with the control group (P<0.05). Results showed that Zizyphus jujuba seed essential oil significantly suppressed LPS-stimulated THP-1 migration and invasion by inhibiting MMP-9 expression and activity (P<0.05). Zizyphus jujuba seed essential oil could inhibit THP-1 migration and invasion induced by LPS by suppressing MMP-9 expression, providing a theoretical foundation for the clinical treatment of osteoarthritis with Zizyphus jujuba seed essential oil.

Essential oils are complex mixtures of several components endowed with a wide range of biological activities, including anticancer properties. Due to the side effects and the resistance of synthetic drugs, plant products are considered for the treatment of cancer. This study is performed the effect of cytotoxicity of essential oil from the seeds of Zizyphus jujuba (EOSZ) on K562 cell line as a model of chronic myeloid leukemia. In this study, the seeds of Z. jujube were collected from the Isfahan city, and essential oils were extracted by Clevenger apparatus and then the combination by gas chromatography and spectrophotometry were identified. K562 cells were cultured and treated with concentrations of essential oils of 1 to 900 micrograms per milliliter (in 24h, 48h, and 72h). Cytotoxicity of essential oil from the seeds of Zizyphus jujuba (EOSZ) against K562 leukemia cells was estimated by the MTT assay. The absorbance was measured using ELISA plate reader (540 nm) were measured. Then the data were analyzed with the computer software SPSS version 15. 0 (SPSS Inc. , Chicago, USA), t. test and ANOVA. 24 compounds were identified in the essential oil, the main component of which was Eugenol. Essential oil from the seeds of Zizyphus jujuba (EOSZ), the highest cytotoxic effect in LC50 = 200 micrograms per milliliter and 72 hours after treatment. In other words, the seed essential oil from Zizyphus jujuba (EOSZ) expresses the effects of cellular toxicity on k562 cells, depending on the dose and time. Considering the toxicity of seed essential oil from Zizyphus jujuba (EOSZ), seed essential oil from Zizyphus jujubacan be considered a Potential candidate for further CML studies, and other cancer cells.