## 4 Bioactive Properties
### Antitumor Effects  
In the past few decades, the cytotoxicity of sesquiterpenes and sesquiterpene derivatives from the _Ferula_ species, especially sesquiterpene counarins, has been studied extensively. These compounds have shown significant cytotoxicity against various tumor cell lines, including HCT116 and HT-29 human colon cancer cells; AGS, BGC-823, and MGC-803 human gastric cancer cells; M4 Beu human melanoma cells; BxPC3, PANC-1, and Capan-1 human pancreatic cancer cells; HeLa human cervical cancer cells; and MCF-7 and MDA-MB-231 human breast cancer cells. The IC\({}_{50}\) values of these compounds against different cancer cell lines in vitro are listed in Table 6.  
Umbelliprennin (**150**) is one of the most widely studied sesquiterpene counarins with antitumor potential. Promoting tumor cell apoptosis is one of the important mechanisms in antitumor therapy. Researchers discovered that umbelliprennin (**150**) could promote apoptosis in tumor cells by annexin V-FITC/PI staining. In the meanwhile, umbelliprennin (**150**) activated caspase-3, -8, and -9 and the proapoptotic protein Bax and reduced the expression of the antiapoptotic protein Bcl-2, caspase-3, -8, and -9, and the proapoptotic protein Bax and reduced the expression of the antiapoptotic protein Bcl2 [230; 231], which promoted apoptosis in the Jurkat T-CLL and Raji B-CLL cell lines in a time- and dose-dependent manner [232]. In addition, it could activate the mitochondrial apoptotic pathway and lead to apoptosis of the cancer cells by decreasing the mitochondrial membrane potential, enhancing the P53, P27, P16, and Rb protein expression and diminishing the expression of the proteins of cyclin E, cyclin D, Cdk4, and Cdk6 as well as cell cycle arrest in the G0/G1 phase [233]. Apart from this, umbelliprennin (**150**) could attenuate cell migration through the Wnt signaling pathway by decreasing the expression levels of Wnt-2, \(\beta\)-catenin, GSK-3\(\beta\), p-GSK-3\(\beta\), survivin, and c-myc [193]. In another study, umbelliprennin was found to induce cytoprotective autophagy by reducing the phosphorylation levels of AKT and mTOR and blocking the Akt signaling pathway [230]. In brief, umbelliprennin (**150**) could exert its antitumor property by inducing apoptosis and autophagy, inhibiting the cell cycle, and attenuating the migration and invasion of cancer cells. In an in vivo study, a double-stage carcinogenicity assay of mouse skin tumors was performed to investigate the cancer chemoprerevity of umbelliprenin (**150**). The results showed that mice treated with umbelliprenin (**150**) together with peroxynitrtite (initiator)/TPA (promoter) had delayed papillary tumor formation, with effects comparable to those of the curcumin control. Furthermore, the tumor development pattern was slower in umbelliprenin-treated mice compared with curcumin treatment. Thus, umbelliprenin (**150**) may be a potential cancer chemoprereentive agent [234]. Galbanic acid (**213**) is another extensively studied sesquiterpene coumarin. [PERSON] et al. [235] revealed the potential molecular mechanism of galbanic acid (**213**) in overcoming chemotherapy resistance in drug-resistant lung cancer. As an effective TNF-related apoptosis-inducing ligand (TRAIL) sensitizer, galbanic acid (**213**) enhanced TRAILIL-induced cell apoptosis by inhibiting multidrug resistance 1 (MDR1) and activating caspase and death receptor 5 (DR5) in cisplatin-resistant H460/R non-small-cell lung cancer cells. Galbanic acid (**213**) induced tumor cell-cycle arrest at G1, which is associated with the inhibition of the cyclin/cyclin-dependent kinase (CDK)4/6 pathway, particularly cyclin D1. [236]. It also inhibited tumor cell metastasis. Neoangiogenesis and the activation of matrix metalloproteinases (MMPs) play a crucial role in tumor generation and metastasis. Neovessels are formed during tumor generation and metastasis [237], so the inhibition of angiogenesis may promote cancer cell death [238]. [PERSON] et al.