The developers of a compound that makes bladder cancer cells sensitive to light say inhibiting autophagy in the cells before treatment makes them even more susceptible to the drug.
The photosensitizing agent chlorophyllin e4 is a semi-synthetic compound mixture of sodium copper salts derived from chlorophyll. A 2012 study by scientists at Fudan University in Shaghai found that chlorophyllin e4 “exhibited significant photocytotoxicity” in two kinds of bladder cancer cells, killing 82% of one kind an 85% of another when exposed to a strong laser light in the laboratory.
In their newest studies published in the Journal of Photochemistry and Photobiology and in Lasers in Surgery and Medicine, the same team found that inhibiting the process by which cells breaks down dysfunctional cellular components (authophagy) made them more sensitive to the cytotoxic effects of both chlorophyllin e4 and a similar compound they called chlorophyllin f.
Noting that the chlorophyllin e4 tended to collect in the lysosome and mitochondria, they found that bladder cancer cells were able to help protect themselves against chlorophyllin-induced light sensitivity by destroying these cell components through autophagy. When autophagy was inhibited with a drug, the bladder cancer cells exhibited “much lower cell viability and higher apoptotic cell death”.
Summarizing their results, lead researcher Lihuan Du of the Department of Urology at Fudan University writes, “Thus, these data imply that the combination of PDT, when mediated by our new photosensitizer chlorophyllin e4 and an autophagy inhibitor, might be a promising approach to the elimination of non-muscle invasive bladder cancer.”
Bladder cancer is the sixth most common cancer in the US and is more common among diabetics, especially if they have been treated with the drug Actos. People with diabetes already have an elevated risk of bladder cancer and several studies have indicated that Actos compounds the risk. Whether or not Actos use was the cause, most cases of bladder cancer in diabetics are transitional cell carcinomas that begin in the lining of the bladder. Fortunately, bladder cancer in diabetics usually responds to treatment.
Du, L et al, “Autophagy inhibition sensitizes bladder cancer cells to the photodynamic effects of the novel photosensitizer chlorophyllin e4”, February 27, 2014, Journal of Photochemistry and Photobiology, Epub ahead of print
Du, L, et al, “Photodynamic therapy with the noel photosensitizer chlorophyllin f induces apoptosis and autophagy in human bladder cancer cells”, January 24, 2014, Lasers in Surgery and Medicine, Epub ahead of print