Investigation Of Small Molecule-Induced Apoptosis And The Apoptosis-Molecular Mechanisms In A549 Human Lung Cancer Cells

BACKGROUND AND OBJECTIVEIn recent years, lung cancer is the leading category of cancer threatening the health of the people in many countries. In lung carcinomagenesis, China has ranked the first in the world. Lung cancer mortality stands the first within all kinds of cancer death. Moreover, among all types of lung cancer, adenocarcinoma occurs most commonly and its incident rate is the highest. Therefore, to cure lung adenocarcinoma is the key to reduce lung cancer mortality rate.However, no effective treatments for lung adenocarcinoma could be available now, because the molecular mechanisms underlying lung adenocarcinoma apoptosis have not been clarified. So, it is in urgent need of elucidating the apoptotic mechanisms.Chemical genetics provides a new strategy for studying the mechanisms underlying tumor apoptosis. For example, according to chemical genetics, small molecule PRIMA-1 was used to interfere signal transduction net- work in malignant colon cell lines. The results showed that PRIMA-1 increased p21 and GADD45 expression selectively in the mutant p53 cells, blocked cell cycle at G₂ phase, and JNK pathway played an important role in PRIMA-1-induced apoptosis. However, Fas, Bcl-2 family proteins, and caspases were not involved in the cell death. Furthermore, small molecule HA14-1 promoted apoptosis in several types of cancer cell lines, including breast cancer (MDA-MB-468), by interrupting the function of Bcl-2 protein, decrease of mitochondria membrane potential, activation of casapse-9, -3. Many reports show that small molecules can directly bind with their target proteins, and can be used to realize the real-time investigation of the dynamic changes in cells. Moreover, small molecules are powerful tool used to study the signal transduction in cells.