Scenario: You’re at my house for a dinner and I make you a mind-blowing chocolate tart. You ask why it is so durn good, and I pass along the fact that Nutella is the ass-kicking ingredient. Next thing you know, you’re trying to add Nutella to everything at home….and by golly, it makes (many) things taste better. Today’s image is from a paper characterizing the relationship between the many cellular changes after treatment by antimitotic drugs. Knowing how these drugs work (by analogy, finding the ass-kicking “ingredient”) can help folks develop improved anti-cancer drugs.Many anticancer drugs are antimitotic drugs, meaning they function by blocking the progress of cell division during mitosis. In addition to arresting mitosis, these drugs cause apoptosis, DNA damage, and induction of p53 (a tumor suppressor gene), and a recent paper investigates the relationship between all of these events. After treating cells with powerful antimitotic drugs, Orth and colleagues found that the resulting prolonged mitotic arrest (or slippage from that arrest) causes DNA damage, which in turn causes an induction of p53. The DNA damage was inhibited when these treated cells were prevented from launching the pathway for apoptosis, which is programmed cell death. So, Orth and colleagues concluded that the prolonged mitotic arrest caused by antimitotic drugs results in a partial activation of apoptosis. Understanding this partial apoptotic response in the context of treating tumors should help guide development of improved cancer therapies. The images above show increasing DNA damage (red spots) after prolonged treatment with an antimitotic drug, compared with an untreated cell (top left). By 16 and 48 hours of drug treatment (bottom), cells had very high levels of DNA damage. Arrows point to mitotic cells.
Orth, J., Loewer, A., Lahav, G., & Mitchison, T. (2011). Prolonged mitotic arrest triggers partial activation of apoptosis, resulting in DNA damage and p53 induction Molecular Biology of the Cell, 23 (4), 567-576 DOI: 10.1091/mbc.E11-09-0781
very cool study. I'm familiar with this area of research and no previous paper has taken it this far...not even high-profile papers. Cool work and nice image.
ReplyDeleteBest DNA damage during mitotic arrest paper I've seen. Other papers hinted at it but fell short on mechanism. The supplemental data alone represents another paper's worth of data!
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