*4.15. N-Phenethylacetamide*

N-Phenethylacetamide (NPA) is found in the *Aquamarina Sp.* (MC085). Three compounds, two diketopiperazines [cyclo(L-Pro-L-Leu) (1) and cyclo(L-Pro-L-Ile) (2), and one NPA (3)] isolated with anti-cancer activity. By altering TGF-induced E.M.T., NPA inhibits the TGF/Smad pathway and suppresses A549 cell metastasis. It prevents Snail and Slug expression by inhibiting Smad 2/3 phosphorylation. It also suppresses Snail and Slug, which upregulates the epithelial markers E-cadherin, Zo-1, and claudin-1 while downregulating VIM, FN1, CDH2, and MMP-2 expression, preventing metastasis [101]. The mechanism of NPA is shown in Figure 4.

#### *4.16. α-Solanine*

α-Solanin (AS), a steroidal glycoalkaloid obtained from nightshade (Solanum nigrum Linn.), suppresses tumor cell growth and causes apoptosis in colon, liver, cervical, lymphoma, and stomach cancer cells. However, the mechanism by which it blocks cancer cell metastasis remains unknown. An animal model of BC induces cell death and inhibits cell proliferation and angiogenesis, resulting in chemotherapeutic actions [103,104]. It also increases E-cadherin expression, reducing VIM expression and cell invasion, which inhibits EMT. It also decreases extracellular inducer of matrix metalloproteinase (EMM-PRIN), MMP-2, and MMP-9, increasing Cysteine-rich protein with Kazal motifs (RECK), TIMP-1, and TIMP-2 mRNA expression levels. It downregulated the phosphorylation of Akt, ERK1/2, and PI3K. Furthermore, it increases tumor suppressor miR-138 expression while decreasing oncogenic miR-21 expression [6,105].

#### *4.17. Baicalein, Wogonin (WG), and Oroxylin-A (ORA)*

Baicalein (BAI), wogonin (WG), and oroxylin-A (ORA) are present in a plant, namely *Scutellaria baicalensis* [105]. It has been reported that the extract of *Scutellaria baicalensis* has anti-tumor activity. A study reported that using the combination of BAI (65.8%), WG (21.2%), and ORA (13.0%) compounds against A549 lung adenoma cancer cells inhibited the EMT process significantly [105]. The Total Flavonoid Aglycones Extract (TFAE) isolated from *Scutellaria baicalensis* has shown inhibition against tumors by inducing apoptosis, mainly BAI, WG, and ORA [106]. It was reported that the TFAE of *Scutellaria baicalensis* has inhibited the EMT of A549 cells via PI3K/AKT-TWIST1 axis [105].
