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Anticancer activities of selected Emirati Date (Phoenix dactylifera L.) varieties pits in human triple negative breast cancer MDA-MB-231 cells.

ABSTRACT: The date palm (Phoenix dactylifera L.) is an important fruit crop with significant pharmaceutical potential. Little data are available on comparative pharmaceutical importance of the date pits. We designed this study to assess the antitumorigenic effects of date palm pits extracts from different Emiratis varieties. We used MDA-MB-231 cells derived from triple negative breasts cancer tissues as a model. We found that out of the 17 date pits extracts from 6 Emiratis varieties, three (Khalas extract in water + acetone (1:1), Abu-Maan extract in MeOH + Chloroform (1:1) and Mabroom extract in water + acetone (1:1)) were found effectively cytotoxic and changed morphology of cells in dose and time dependent manner. We found the maximum effect at 2.5 mg/mL concentration at 72 h. We calculated IC50 values for these varieties at 24 h. IC50 values for Khalas, Abu-Maan and Mabroom were 0.982 mg/mL, 1.149 mg/mL and 2.213 mg/mL respectively. We treated the cells with IC50 values of extracts and observed changes in protein profile using human kinase array kit. After analyzing the results, we suggest that EGFR/ERK/FAK pathway, eNOS and src family proteins are targets of these extracts. We conclude that date pits extracts can be a possible therapeutic agent against cancer and we suggest further studies.

SUBMITTER: Khattak MNK

PROVIDER: S-EPMC7715048 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Anticancer activities of selected Emirati Date (<i>Phoenix dactylifera</i> L.) varieties pits in human triple negative breast cancer MDA-MB-231 cells.

Khattak Muhammad Nasir Khan MNK Shanableh Abdallah A Hussain Muhammad Iftikhar MI Khan Amir Ali AA Abdulwahab Muhammad M Radeef Wameed W Samreen Mohammad Harb MH

Saudi journal of biological sciences 20200906 12

The date palm (<i>Phoenix dactylifera</i> L.) is an important fruit crop with significant pharmaceutical potential. Little data are available on comparative pharmaceutical importance of the date pits. We designed this study to assess the antitumorigenic effects of date palm pits extracts from different Emiratis varieties. We used MDA-MB-231 cells derived from triple negative breasts cancer tissues as a model. We found that out of the 17 date pits extracts from 6 Emiratis varieties, three (Khalas ...[more]

PMID: 33304147

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Project description:Due to its nutritional value and health benefits, the date palm (Phoenix dactylifera L.) is an essential dietary food crop throughout Middle Eastern and African countries. Consumers are concerned about the possible microbial contamination of dates, especially since most dates arriving in local markets are unprocessed. The absence of processing increases the possibility of microbial contamination, which raises the probability of microbial contamination. This study aims to analyze and evaluate the variability of fungal and bacterial microbiota identified in the most popular date palm fruits in Saudi Arabia. The study assessed ten date variety fruits from the most popular date palm varieties for consumption in Saudi Arabia and analyzed the microbial count. Morphological and molecular characterization and comparison of nuclear ribosomal DNA internal transcribed spacer (ITS) sequences identified 78 fungi, including 36 distinct species across 15 fungal genera. Alternaria, Fusarium, Curvilaria, Aspergillus, and Penicillium were the most frequent genera among the ten fruit cultivars studied, according to ITS-rDNA sequence analysis. Furthermore, 36 bacterial isolates were obtained from ten date varieties studied, each with a unique colony morphology. These isolates were identified based on sequence alignment and comparison of their 16S rDNA internal spacer regions to those available in public databases. The results showed that the bacterial isolates included 15 species from five bacterial genera. The results suggested that Bacillus, Stenotrophomonas, and Brucella were the prevailing genera among the ten tested fruit varieties. Some bacterial genera, such as Brucella, Achromobacter, and Stenotrophomonas, are well-known potential human pathogens. Chaetomium globosum was also recognized as air pollution causing adverse health effects such as allergies and as the causal agent of human fungal infections among the tested date varieties; the Rashodiah type exhibited the highest fungal contamination, whereas the Sagai variety displayed the lowest fungal contamination. Conversely, the Sukkari, Barhi, and Mejdool varieties were the most contaminated with bacteria among the ten tested varieties, while the Khalas variety showed the least bacterial contamination. To the best of the authors' knowledge, this study provides the initial comprehensive account of the molecular and morphological identification of all fungal and bacterial genera associated with date palm (P. dactylifera) fruits.

Project description:Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions. Parental MDA-MB-231 cells and MDA-MB-231(SA) cells were cultured in cell culture flasks. RNA was isolated in order to compare the gene expression profiles of these cell variants. Total of two samples. No replicates.

Project description:Breast cancer remains a leading cause of death in women worldwide. Although breast cancer therapies have greatly advanced in recent years, many patients still develop tumour recurrence and metastasis, and eventually succumb to the disease due to chemoresistance. Citral has been reported to show cytotoxic effect on various cancer cell lines. However, the potential of citral to specifically target the drug resistant breast cancer cells has not yet been tested, which was the focus of our current study.The cytotoxic activity of citral was first tested on MDA-MB-231 cells in vitro by MTT assay. Subsequently, spheroids of MDA-MB-231 breast cancer cells were developed and treated with citral at different concentrations. Doxorubicin, cisplatin and tamoxifen were used as positive controls to evaluate the drug resistance phenotype of MDA-MB-231 spheroids. In addition, apoptosis study was performed using AnnexinV/7AAD flowcytometry. Aldefluor assay was also carried out to examine whether citral could inhibit the ALDH-positive population, while the potential mechanism of the effect of citral was carried out by using quantitative real time- PCR followed by western blotting analysis.Citral was able to inhibit the growth of the MDA-MB-231 spheroids when compared to a monolayer culture of MDA-MB-231 cells at a lower IC50 value. To confirm the inhibition of spheroid self-renewal capacity, the primary spheroids were then cultured to additional passages in the absence of citral. A significant reduction in the number of secondary spheroids were formed, suggesting the reduction of self-renewal capacity of these aldehyde dehydrogenase positive (ALDH+) drug resistant spheroids. Moreover, the AnnexinV/7AAD results demonstrated that citral induced both early and late apoptotic changes in a dose-dependent manner compared to the vehicle control. Furthermore, citral treated spheroids showed lower cell renewal capacity compared to the vehicle control spheroids in the mammosphere formation assay. Gene expression studies using quantitative real time PCR and Western blotting assays showed that citral was able to suppress the self-renewal capacity of spheroids and downregulate the Wnt/?-catenin pathway.The results suggest that citral could be a potential new agent which can eliminate drug-resistant breast cancer cells in a spheroid model via inducing apoptosis.

Project description:The present study was carried out to assess the status of various hormones responsible for the flower induction of Nagal, Lulu, and Khalas date palm varieties in UAE. The nonenzymatic antioxidant compounds and the antioxidant enzymatic activities at preflowering, flowering, and postflowering stages of the date palm varieties were quantified. The ABA and zeatin concentrations were found to be significantly higher during the preflowering stage but gradually decreased during the flowering period and then increased after the flowering stage. Gibberellic acid (GA) concentrations were significantly higher in the early flowering varieties and higher levels of ABA may contribute to the delayed flowering in mid and late varieties. The results on hormone profiling displayed a significant variation between seasons (preflowering, flowering, and postflowering) and also between the three date palms (early, mid, and late flowering varieties). Ascorbic acid (AA) concentration was low at the preflowering stage in the early flowering Nagal (0.694 mg/g dw), which is similar with the late flowering Lulu variety (0.862 mg/g dw). However, Khalas variety showed significantly higher amount of AA content (7.494 mg/g dw) at the preflowering stage when compared to other varieties. In flowering stage, Nagal (0.814 mg/g dw) and Lulu (0.963 mg/g dw) were similar with respect to the production of AA, while the mid flowering variety showed significantly higher amount of AA (9.358 mg/g dw). The Khalas variety produced the highest tocopherol at 4.78 mg/g dw compared to Nagal and Lulu, at 1.997 and 1.908 mg/g dw, respectively, during the preflowering stage. In Nagal variety, the content of reduced glutathione (GSH) at the preflowering stage was 0.507 mg/g dw, which was not significantly different from the flowering and postflowering stages at 0.4 and 0.45 mg/g dw, respectively. The GSH was significantly higher in Khalas compared to Nagal and Lulu varieties, at 1.321 mg/g w in the preflowering phase followed by 3.347 mg/g dw and 2.349 mg/g dw at the flowering and postflowering phases, respectively. Catalase activity increased with different stages of growth. The lowest catalase activity was observed at the preflowering stage in Khalas (0.116), with similar observations noted during flowering (0.110) and postflowering stage. This study provides an insight into the possible roles of endogenous hormones and antioxidants and in the activities of antioxidant enzymes in the regulation of flower development in date palm varieties.

Dataset Information

Anticancer activities of selected Emirati Date (Phoenix dactylifera L.) varieties pits in human triple negative breast cancer MDA-MB-231 cells.

Publications

Anticancer activities of selected Emirati Date (<i>Phoenix dactylifera</i> L.) varieties pits in human triple negative breast cancer MDA-MB-231 cells.

Similar Datasets

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