# COX2-Inhibitory and Cytotoxic Activities of Phytoconstituents of _Matricaria chamomilla_ L.
## 4 Discussion
The main concept of our research efforts is to find cytotoxic compounds that can be used as functional food ingredients with negative side effects and that are able to bypass multidrug resistance or even provoke collateral sensitivity in resistant tumor cells [112; 113; 114; 115]. Myricetin is a flavonoid present in tea, wine, fruits, and vegetables [116]. For decades, myricetin has been recognized for its antioxidant, anticancer, antidiabetic, and anti-inflammatory activities [117; 118; 119; 120]. Furthermore, it has been reported that myricetin reduces resistance to anticancer drugs and other cytotoxic agents. Among them were camptothecin and podophyllotoxin by inducing topoisomerase I/II-DNA complex, cisplatin in ovarian and colon cancer cells by inducing apoptosis through Bax/Bcl-2 proteins, resveratrol in an additive manner by inhibiting 12-O-tetradcanoyl phorod-13-acetate (TPA) and EGF, as well as vincristine by blocking ABCC1 (MRP1) and ABCC2 (MRP2) [119; 121; 122]. There are findings that suggest that exposure to carcinogens may not only initiate carcinogenesis but also confer resistance to the very agents used to treat tumors [123; 124; 125; 126]. Moreover, inflammation plays a significant role in the process of carcinogenesis, particularly in prostate and colon cancer. It is common sense that chronic inflammation leads to DNA damage, tissue damage, and abnormal cell growth that can ultimately result in cancer. Chemoprevention is a promising approach to preventing cancer by using natural or synthetic compounds to inhibit the development of cancer at its earliest stages. Several studies have demonstrated that anti-inflammatory agents prevent the initiation, promotion, and progression of cancer by modulating various molecular targets. Therefore, targeting inflammation through chemoprevation may represent a promising strategy for preventing cancer development and progression [127, 128, 129, 130, 131]. Therefore, it is straightforward to elaborate on chamomile, which contains not only myricetin but also various other bioactive compounds, including apigenin, famesol, quercetin, and luteolin, to act as chemoprevents. This notion was supported by our growth inhibition assay, where the chamomile extract demonstrated significant activity against several cancer cell lines. It could, thus, be hypothesized that chamomile tea may help to prevent cancer and also suppress cancer cell growth at the early stages of tumor development. For this reason, we used proteome analysis to gain more insights into the molecular mechanisms underlying the sensitivity and resistance of cancer cell lines to myricetin. The expression of 3171 proteins was determined in the NCI cell line panel [42] and correlated with the log\({}_{10}\)IC\({}_{50}\) values of these cell lines for myricetin in the present investigation. The top 20 directly correlating proteins (indicating myricetin resistance) and the top 20 inversely correlating proteins (indicating myricetin sensitivity) were subjected to hierarchical cluster analysis. The distribution of the myricetin-resistant cell lines in clusters 1 and 2 and the myricetin-sensitive cell lines in cluster 3 was statistically significant (\(p=0.00049\)). The 40 relevant proteins associated with cellular myricetin responsiveness are involved in a variety of multifactorial interactions. The formation of clusters A-D has been performed to better illustrate the distribution of protein expression in clusters 1-4 (i.e., red and green fields). The assembly of proteins in clusters A-D occurred according to their degrees of protein up- or downregulation in the specific tumor cell lines. A preferential assembly of the molecular and cellular functions of these proteins was not observed in clusters A-D.