Light-Activated Molecules Trigger Double Stranded DNA Damage That Kills Cancer Cells

Cancer researchers have developed a panel of chemotherapeutic agents that induce apoptosis in tumor cells by causing damage to the cancer cells' double stranded DNA when exposed to light.

Investigators at Florida State University (Tallahassee, USA) worked with a class of reagents known as simple lysine conjugates. These small molecules were known to be capable of selective DNA damage at sites approximating a variety of naturally occurring DNA-damage patterns. This process transformed single-strand DNA cleavage into double-strand cleavage. Cells are incapable of repairing double-strand damage, which triggers apoptotic pathways.

An essential property of lysine conjugates is their activation by certain wavelengths of light. Thus, the molecules' photoactivated cancer-killing properties are expressed upon demand only when the reagents are in exactly the right place and when their concentration is high inside the cancer cells. Results published in the August 7, 2007, online edition of the Proceedings of the [U.S.] National Academy of Sciences revealed that, while several lysine conjugates demonstrated little effect upon cultured cancer cells -- in this case, metastatic human kidney cancer cells -- without light, upon phototherapy activation they killed more than 90% of the cancer cells with a single treatment.

"When one of the two strands of our cellular DNA is broken, intricate cell machinery is mobilized to repair the damage,” said contributing author Dr. Igor V. Alabugin, associate professor of chemistry and biochemistry at Florida State University. "Only because this process is efficient can humans function in an environment full of ultraviolet irradiation, heavy metals, and other factors that constantly damage our cells. In our research, we are re working on ways to induce apoptosis in cancer cells by damaging both of their DNA strands. We have found that a group of cancer-killing molecules known as lysine conjugates can identify a damaged spot in a single strand of DNA and then induce cleavage on the DNA strand opposite the damage site. This double cleavage of the DNA is very difficult for the cell to repair and typically leads to apoptosis.”


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