Cell Division Aberrations Caused by Cigarette Smoke Could Help Detect Cancer Early

Consequently, centrosome amplification induces programmed cell death. But cancer cells have a clever workaround. When threatened with centrosome amplification, they are able to cluster their excess centrosomes at either pole, fooling the cell division machinery into pseudo normalcy. Thus, cell division continues, and the cancer cell is able to continue its malignancy. One of the most important causes of lung cancer is tobacco smoking. According to the American Cancer society, about 84% of women and 90% of men who have been newly diagnosed with lung cancer are either current smoker or have smoked in the past. Tobacco smoke contains a number of chemicals, including nicotine, tar, nitrosamines and benzo[a]pyrenes that can introduce genetic instability in the lung’s epithelial cells and initiate cancer development. Thus, El-Zein and Thaiparambil examined if exposure to cigarette smoke increases centrosome number in the lung’s epithelial cells. For their experiments, they prepared cigarette smoke condensate by exposing cell culture media to cigarette smoke. Then, the normal human lung epithelial cells were allowed to grow in this culture media cells were monitored for mitotic aberrations periodically for up to 72 hours. Consistent with previous studies, they found that the chemicals in cigarette smoke-induced centrosome amplification. But they also found that cigarette smoke also caused centrosome clustering in normal epithelial cells. “When a cell sustains DNA damage, its repair machinery will fix it. When it can’t, then there is an accumulation of problems like centrosome amplification,” said Thaiparambil. “And then if the centrosomes begin to cluster and the cell divides, the normal cell begins to turn into a cancer cell.” Next, the researchers investigated if turning off certain genes could arrest centrosome amplification and thereby rescue the cells from a path toward cancer. In their previous study, they showed that when lung epithelial cells are exposed to nitrosamines and benzo[a]pyrenes, two chemicals in cigarette smoke, the sonic hedgehog, FOXM1 and CCND2 were overexpressed. For the current study, they silenced these genes in the lung epithelial cells and then re-exposed the cells to the cigarette smoke condensate. When Thaiparambil examined these cells, they neither had centrosome amplification or clustering. The researchers noted that their results are a promising avenue for both detecting very early stages of lung cancer and possible intervention. “There are several drugs actually out there that can target certain genes and reduce their overexpression,” said El-Zein. “So, the genes that are involved in centrosome amplification could be targeted to prevent the cancer from taking hold among high-risk smokers.”