C. spinosa L. subsp. rupestris Phytochemical Profile and Effect on Oxidative Stress in Normal and Cancer Cells

Abstract

Spices, widely used to improve the sensory characteristics of food, contain several bioactive compounds as well, including polyphenols, carotenoids, and glucosynolates. Acting through multiple pathways, these bioactive molecules affect a wide variety of cellular processes involved in molecular mechanisms important in the onset and progress of human diseases. Capparis spinosa L. is an aromatic plant characteristic of the Mediterranean diet. Previous studies have reported that different parts (aerial parts, roots, and seeds) of C. spinosa exert various pharmacological activities. Flower buds of C. spinosa contain several bioactive compounds, including polyphenols and glucosinolates. Two different subspecies of C. spinosa L., namely, C. spinosa L. subsp. spinosa, and C. spinosa L. subsp. rupestris, have been reported. Few studies have been carried out in C. spinosa L. subsp. rupestris. The aim of our study was to investigate the phytochemical profile of floral buds of the less investigated species C. spinosa subsp. rupestris. Moreover, we investigated the effect of the extract from buds of C. spinosa subsp. rupestris (CSE) on cell proliferation, intracellular ROS levels, and expression of the antioxidant and anti-apoptotic enzyme paraoxonase-2 (PON2) in normal and cancer cells. T24 cells and Caco-2 cells were selected as models of advanced-stage human bladder cancer and human colorectal adenocarcinoma, respectively. The immortalized human urothelial cell line (UROtsa) and human dermal fibroblast (HuDe) were chosen as normal cell models. Through an untargeted metabolomic approach based on ultra-high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS), our results demonstrate that C. spinosa subsp. rupestris flower buds contain polyphenols and glucosinolates able to exert a higher cytotoxic effect and higher intracellular reactive oxygen species (ROS) production in cancer cells compared to normal cells. Moreover, upregulation of the expression of the enzyme PON2 was observed in cancer cells. In conclusion, our data demonstrate that normal and cancer cells are differentially sensitive to CSE, which has different effects on PON2 gene expression as well. The overexpression of PON2 in T24 cells treated with CSE could represent a mechanism by which tumor cells protect themselves from the apoptotic process induced by glucosinolates and polyphenols.

The Role of NQO1 in Ovarian Cancer

“…Nuclear Factor Erythroid 2-Related Factor 2 (NFE2L2 or NRF2)/Kelch Like ECH Associated Protein 1 (KEAP1) signalling is one of the most important pathways involved in chemoresistance onset and cancer progression [14,57,58]. In fact, NRF2 can bind the antioxidant response element (AREs) regions present in the promoter of several antioxidant genes such as NQO1, superoxide dismutase (SOD), catalases (CATs), thioredoxins (Trxs), peroxiredoxins (Prxs), reductases and peroxidases inducing their expression and counteracting the oxidant effects of platinum-based chemotherapeutics, then leading to chemoresistance in these cells [14,57,[59][60][61].…”

The Contribution of Oxidative Stress to NF1-Altered Tumors

“…The potential enhanced effect of chemotherapeutic drugs in the presence of antioxidants is interesting. Different compounds (nutrients, extracts from plants, enzymes) known to be relevant sources of antioxidants have been tested in order to increase the activity of anticancer drugs, both to enhance cytotoxicity and alleviate unwanted toxicity to vital tissues [ 81 , 82 , 83 , 84 , 85 ]. However, the beneficial role of antioxidants associated with chemotherapy is still debated, regarding their alleged and already mentioned protective role towards cancer cells [ 86 ]…”

Redox Regulation of Autophagy in Cancer: Mechanism, Prevention and Therapy

“…PON2 reduces the release of O 2 – from the inner mitochondrial membrane, thus protecting cells from oxidative stress [ 23 , 24 ]. Studies have proved that PON2 is overexpressed in some solid tumors, and it has been proposed as a therapeutic target for several malignant tumors such as glioblastoma multiforme, bladder cancer and melanoma [ 25 , 26 , 27 , 28 ]. The source and conversion of active oxygen are shown in Figure 1 .…”