*4.3. Eugenol*

A polypropanoid group of compounds is found in seeds of many plants, such as cloves, cinnamon, nutmeg, and bay leaves. It has antioxidant, anti-bacterial, anti-inflammatory, and anti-cancer activity and is widely used as a cosmetic, perfume, and culinary ingredient. It has anti-cancer potential due to its ability to increase reactive oxygen species (ROS) formation and apoptotic action, increase Cyt C's release, and inhibit the EMT process, limiting the cells' ability to metastasize [65]. It has shown anti-cancer activity against malignancies, including leukemia, lung, colon, colorectal, skin, gastric, breast, cervical, and prostate cancer, through the processes described below in Table 3.


**Table 3.** Mechanisms of Eugenol for anti-apoptotic in various cancers.

#### *4.4. Resveratrol*

Resveratrol (RES) chemically trihydroxy stilbene is a polyphenol in grapes, berries, peanuts, and wine. RES has been shown to have cardioprotective, anti-inflammatory, and

anti-aging effects. Studies also suggest that it also has anti-cancer properties. Moreover, RES has a regulatory role in EMT and the hedgehog (Hh) signaling pathway, which is critical for vertebrate development, homeostasis, and cancer. Hh is abnormally activated in breast, prostate, and pancreatic cancer (PC) and has a role in metastasis and invasion of GC via induction of the EMT. Hence, Hh signaling pathway is the center of attraction for anti-cancer activity. RES suppresses the Hh pathway, thus inhibiting cancer invasion and metastasis.

Moreover, RES has also been shown to block the Hh signaling pathway and EMT in malignancies [71]. A study proved that RES inhibited EMT in Glioblastoma (GBM) cells, as evidenced by morphological changes in the RES-treated G.B.M. cells. RES also inhibits EMTmediated migration and invasion of GBM cells and EMT-induced stem cell-like properties in GBM cells [72]. A TGF-β/Smad signaling pathway is associated with the proliferation, differentiation, and migration of the cells and promotes results in invasion and metastasis. RES inhibited the penetration and metastasis by EMT-induced phosphorylation of Smad2 and Smad3 in a dose-dependent manner, suggesting the function of RES on EMT is related to Smad-dependent signaling [72].
