Dataset Information

Selective in vitro cytotoxicity effect of Drimia calcarata bulb extracts against p53 mutant HT-29 and p53 wild-type Caco-2 colorectal cancer cells through STAT5B regulation.

ABSTRACT: Colorectal cancer is the fourth leading cause of oncological-related deaths and the third most diagnosed malignancy, worldwide. The emergence of chemoresistance is a fundamental drawback of colorectal cancer therapies and there is an urgent need for novel plant-derived therapeutics. In this regard, other compounds are needed to improve the efficacy of treatment against colorectal cancer. Medicinal plants have been effectively used by traditional doctors for decades to treat various ailments with little to no side effects. Drimia calcarata (D. calcarata) is one of the plants used by Pedi people in South Africa to treat a plethora of ailments. However, the anticancer therapeutic use of D. calcarata is less understood. Thus, this study was aimed at evaluating the potential anticancer activities of D. calcarata extracts against human colorectal cancer cells. The phytochemical analysis and antioxidant activity were analysed using LC-MS, DPPH, and FRAP. The inhibitory effects and IC50 values of D. calcarata extracts were determined using the MTT assay. Induction of cellular apoptosis was assessed using fluorescence microscopy, the Muse® Cell Analyser, and gene expression analysis by Polymerase Chain Reaction (PCR). Water extract (WE) demonstrated high phenolic, tannin, and flavonoid contents than the methanol extract (ME). LC-MS data demonstrated strong differences between the ME and WE. Moreover, WE showed the best antioxidant activity than ME. The MTT data showed that both ME and WE had no significant activity against human embryonic kidney Hek 293 cell line that served as non-cancer control cells. Caco-2 cells demonstrated high sensitivity to the ME and demonstrated resistance toward the WE, while HT-29 cells exhibited sensitivity to both D. calcarata extracts. The expression of apoptosis regulatory genes assessed by PCR revealed an upregulation of p53 by ME, accompanied by downregulation of Bcl-2 and high expression of Bax after treatment with curcumin. The Bax gene was undetected in HT-29 cells. The methanol extract induced mitochondrial-mediated apoptosis in colorectal Caco-2 and HT-29 cells and WE induced the extrinsic apoptotic pathway in HT-29 cells. ME downregulated STAT1, 3, and 5B in HT-29 cells. The D. calcarata bulb extracts, therefore, contain potential anticancer agents that can be further targeted for cancer therapeutics.

SUBMITTER: Laka K

PROVIDER: S-EPMC8233163 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Functional foods, beyond basic nutrition, offer health benefits to consumers thanks to the presence of bioactive compounds such as some phytochemicals [1,2]. Today, these foods are of particular interest in biomedical research due to their chemopreventive potential, as they have been shown to induce various biological effects on tumor cells, including the ability to inhibit cell proliferation, induce apoptosis, arrest cell cycle progression, and increase reactive oxygen species [3,4]. Multiple studies have confirmed the relationship between diet and the onset and progression of colorectal cancer (CRC), a malignant neoplasm that arises in the lining of the colon and/or rectum. Therefore, finding foods that can intervene in the carcinogenesis process is an important avenue of research [5,6]. Chlorogenic acid (CGA) is one of the most abundant phenolic compounds in coffee and is also found in fruits and vegetables. Scientific evidence suggests that CGA has chemopreventive potential on CRC cells [7], [8], [9]. For example, in previous studies conducted by our research group, green and roasted coffee extracts were characterized, and this compound was identified as the most abundant [7]. In addition, it was found to significantly decrease cell viability, reduce migration capacity, cause DNA fragmentation, and induce the production of reactive oxygen species in colorectal adenocarcinoma cells cultured in monolayer and treated with different doses of CGA. Furthermore, the mechanism underlying this biological activity has been related to CGA's ability to modulate the Wnt- /β-catenin pathway, which is implicated in the development and progression of CRC [7,10,11]. This paper presents data on the cytotoxic response of CGA treatments on HT-29 cells cultured in a 3D model. To this end, morphological changes in cell spheroids, propidium iodide and DiOC6 uptake, quantification of reactive oxygen species (ROS) production, phosphatidylserine exposure, and cell cycle progression were evaluated by flow cytometry.

Project description:Aloe arborescens is a relevant species largely used in traditional medicine of several countries. In particular, the decoction of leaves is prepared for various medicinal purposes including antidiabetic care. The aim of this research was the study of the antiglycation activity of two A. arborescens leaf extracts and isolated compounds: aloin and aloe-emodin. These phytoconstituents were quantitatively assessed in methanolic and hydroalcoholic extracts using high performance liquid chromatography (HPLC) analysis. In addition, the total phenolic and flavonoid contents were detected. In order to study their potential use in diabetic conditions, the antiglycation and antiradical properties of the two extracts and aloin and aloe-emodin were investigated by means of bovine serum albumin (BSA) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) assays; further, their cytotoxicity in HT-29 human colon adenocarcinoma cells was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, the ability of aloin and aloe-emodin to permeate the cellular membranes of HT-29 cells was determined in order to estimate their potential in vivo absorption. This assessment indicated that aloe-emodin can substantially pass through cell membranes (~20%), whereas aloin did not permeate into HT-29 cells. Overall, the data show that both the methanolic and the hydroalcoholic A. arborescens extracts determine significant inhibition of glycation and free-radical persistence, without any cytotoxic activity. The data also show that the antiglycation and the antiradical activities of aloin and aloe-emodin are lower than those of the two extracts. In relation to the permeability study, only aloe-emodin is able to cross HT-29 cellular membranes, showing the attitude to pass through the intestinal layer. Overall, the present data surely support the traditional use of A. arborescens leaf extracts against hyperglycemic conditions, while aloin and aloe-emodin as potential drugs need further study.

Dataset Information

Selective in vitro cytotoxicity effect of Drimia calcarata bulb extracts against p53 mutant HT-29 and p53 wild-type Caco-2 colorectal cancer cells through STAT5B regulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets