Making light work of a cell's skeleton.

Cancer therapy rarely has a light touch. In the battle against malignant tumors, physicians arm themselves with surgery, radiation, and chemotherapy, treatments potentially as dangerous as cancer itself.

Hoping for a gentler alternative, some researchers have spent more than 2 decades pursuing photodynamic therapy, a strategy in which light kills dye-infused cancer cells (SN: 1/14/89, p.26).

Now, a group from the Dana-Farber Cancer Institute in Boston suggests the method, which has enjoyed limited success, aim for a novel target in the cell: microtubules, the intracellular filaments made from the protein tubulin.

"If you wipe out microtubules, it's a very effective way of killing cancer cells,'' asserts Lan Bo Chen, who heads the Boston team. He notes that many current cancer drugs break up microtubules and that taxol, another well-known anticancer agent, stiffens the filaments. In either case, cells can no longer divide or perform basic maintenance functions, so they rapidly die.

Microtubules began to interest Chen when he, along with Christopher Lee, now at Stanford University, and Samuel S. Wu, now at Stanford University Medical School, investigated cyanine dyes, a class of light-sensitive compounds used in photography.

One such dye, when added to kidney cells grown in the laboratory, concentrates inside the cells in organelles such as mitochondria and the endoplasmic reticulum, they report in the May 15 Cancer Research. When they shine blue light on these cells, it destroys the microtubules but leaves other parts of the cells' skeleton intact.

One reason for the selective destruction may be that microtubules gather near or attach to the endoplasmic reticulum. Chen believes the endoplasmic reticulum releases its dye onto microtubules and free-floating tubulin. The dye, when activated by light, breaks down microtubules and prevents new filaments from forming. "The detailed mechanism we do not know," admits Chen.

Questions remain about the dye's toxicity, whether it can target cancer cells over healthy cells, and whether it can be modified to respond to longer wavelengths of light, which penetrate the body more easily, cautions James W. Foley of the Rowland Institute for Science in Cambridge, Mass.

"At this stage, as far as cancer therapy, I don't think it's very valuable,'' he says. Foley suggests that the dye may hold more immediate interest for cell biologists interested in the function of microtubules.