## 4 Role of Triterpenoids in Cancer Prevention
### Role of Triterpenoids in Tumor Cell Survival, Apoptosis, and Proliferation  
Apoptosis, which in Greek literally means \"falling away,\" is a process of programmed cell death that occurs normally in multicellular organisms. Apoptosis is a natural, organized process that plays an important role in embryonic development and adult tissue equilibrium by adjusting the physiological processes involved. The human body is made up of six trillion cells, with approximately three billion cells replaced every minute. Through the process of apoptosis, the body can eliminate damaged or unneeded cells without local inflammation from the leakage of cell contents [178]. Because deregulation of apoptosis is one of the most important factors involved in tumor cell progression, a number of scientific studies have been done on this process to determine if it can be exploited in cancer treatment. Apoptosis is the human body's mechanism for destroying any cell that has abnormalities such as DNA damage, oncogene activation, nutrient deficiency, or hypoxia. But cancer cells have the ability to escape apoptosis, allowing tumors to grow rapidly and uncontrollably. Apoptosis in cancer cells can be triggered by the activation of proteases such as caspases, leading to the cells' destruction. There are two different pathways by which this apoptosis can be stimulated in cancer cells. The first is the intrinsic pathway through mitochondria, which releases cytochrome C proteins such as second mitochondria derived activator of caspases (SMACs) that bind to and deactivate inhibitor of apoptosis proteins (IAPs), allowing apoptosis to proceed. Apoptotic signals in this pathway may come in the form of members of the Bcl-2 family of proteins such as pro-apoptotic Bax, which can be upregulated by tumor suppressor protein p53 in response to DNA damage [179]. The second pathway is the extrinsic pathway, in which apoptosis is triggered by the activation of proapoptotic receptors such as death receptors 4 and 5 (DR4 and DR5) and Fas, which are present on the cell surface. The activation of the death receptor pathway leads to receptor aggregation, which then initiates the recruitment and activation of initiator caspase-8. While p53 is involved in the intrinsic pathway, it has no role in the extrinsic pathway [178, 180, 181, 182]. STAT3 activation has been associated with cell survival, proliferation, and invasion in various human cancers. Some members of the Bcl-2 family of proteins, such as Bcl-2 and Bcl-xL, also play a role in apoptosis and have been found to be elevated in different types of cancer cells. These proteins cause some cells to develop resistance to drugs used in cancer treatment. Another protein, survivin, may play a role in tumor progression as it has been found at excessive levels in cancer cells. Targets for the treatment of cancer could be those that cause downregulation of the Bcl-2, Bcl-xL, and survivin proteins and upregulation of the p53, Bax, and caspase proteins. Triterpenoids have been found to act through the intrinsic apoptosis pathway to prevent tumor progression. For example, many spice derived triterpenoids have been shown to induce apoptosis in different types of cancer cells through a wide variety of mechanisms. Among the most important of these are asiatic acid, astragaloside, celastrol, cucurbitacin, diosgenin, gypenoside, hederagenin, lupeol, and momordin (Table 2). These triterpenoids have a common target, the antiapoptotic protein Bcl-2, which can induce apoptosis in cancer cells. Pristimerin has been shown to induce mitochondrial cell death in human cancer cells, and the ROS dependent activation of both Bax and poly (ADP-ribose) polymerase-1 (PARP-1) is critically required for mitochondrial dysfunction [117, 183]. In human HL-60 cells, pristimerin also showed antiproliferative effects, with an IC\({}_{50}\) of 0.88 uM [184].