# COX2-Inhibitory and Cytotoxic Activities of Phytoconstituents of _Matricaria chamomilla_ L.
## 4 Discussion  
Chamomile tea has been widely utilized as a spice for food preservation and in traditional medicine. Its phenolic and flavonoid attributes offer anti-inflammatory and antioxidant properties [58]. Extensive research has been conducted on the cellular and molecular mechanisms of chamomile tea constituents against cancer, such as apigenin [59]. Since inflammation is related to carcinogenesis [60], we focused this study on the phytochemical constituents of chamomile tea and their effects against COX2, as well as their anti-inflammatory and cytotoxic activities on cancer cells. In understanding the beneficial effect, phytochemistry plays a crucial role in characterizing the composition of secondary plant metabolites [61]. In chamomile tea, more than 200 substances have been identified from the classes of flavonoids, terpenoids, alkaloids, tannins, and polyphenols [62]. Other teas also contain compounds of these chemical classes, with differences in the specific types and quantities of their substances. For example, chamomile tea does not contain caffeine, while black, green, pu-erh, and oolong teas contain varying high amounts of caffeine [63]. Catechin is found in a very high quantity in green tea due to its minimized antioxidant capacity compared to chamomile, black, and peppermint tea [64; 65], and chamomile tea is also the richest in apigenin in contrast to peppermint tea [66]. The question is whether or not the interaction between these different substances may be synergetic or additive. We suggest that the death of cancer cells is more probable if exposed to a combination of various substances in an additive manner rather than surrendering in a synergistic way, which means that the cell has an evolutionary mechanism predisposed to it. Moreover, the concept has been explored as to whether phytochemicals may act synergistically or additively as chemopreverting agents or if combined with cancer drugs for therapeutic intervention. This has been documented in several studies [67; 68; 69]. COX2 is an enzyme that plays a major role in inflammation and carcinogenesis. Since it is produced only during inflammation to catalyze the conversion of arachidonic acid to different prostaglandandins [70]. Furthermore, arachidonic acid derivatives, including endocannabinoids such as 2-arachidonyl-glycerol, are capable of selectively binding to COX2 to undergo oxygenation and catalysis, resulting in the synthesis of hydroxyl-endoperoxide analogs. The prostaglandin H analog is then converted into glyceryl prostaglandandins, including prostaglandin E2 and prostaglandin I2, which have anti-inflammatory and proliferative properties [71; 72]. Figure 9: Kaplan–Meier statistics of overall survival time (months) for renal clear cell carcinoma correlating with the expression of _COX2_ mRNA obtained from the KMPlotter database. (**A**) All patient profiles: _COX2_ mRNA expression correlates significantly with overall survival time, \(p=1.2\times 10^{-4}\). (**B**) Female patients’ profile: _COX2_ mRNA expression correlates significantly with overall survival time, \(p=3\times 10^{-5}\). (**C**) Patients with low neoantigen load and high _COX2_ expression in their renal clear cell tumors had a worse survival prognosis than those with high _COX2_ expression, \(p=3\times 10^{-5}\). The positive feedback loop between COX2 expression and PGE2 production is involved in multiple cellular mechanisms and pathways, which, among other functions, can contribute to the promotion of tumor growth [73]. Hence, the development of COX2 inhibitors is crucial for treating both inflammation and cancer. Unlike traditional nonsteroidal anti-inflammatory drugs (NSAIDs) that can have severe gastrointestinal side effects due to the suppression of COX1, COX2 selective inhibitors celecoxib, rofecoxib, and valdecoxib have fewer side effects. Nevertheless, it has been observed clinically that COXBs can lead to cardiovascular toxicity [74].