University researchers use innovative strategies to kill prostate cancer cells without harming healthy cells
TUSKEGEE, Ala. (May 26, 2011) — In the United States, the lives of many families are forever altered by the diagnosis of a loved one with cancer. This diagnosis is even more devastating for the at-risk black community. Currently, prostate cancer is the most commonly diagnosed cancer and the second-leading cause of cancer death in men in the United States. A more in-depth look reveals the incidence and death rates for black men are more than doubled those of white men. Black men also have the highest incidence rates of prostate cancer in the world. Although substantial research efforts focus on identifying anti-cancer therapeutic agents, few treatment options (including classical chemotherapeutic agents) have proven to be effective especially in cancer’s most advanced stage, metastasis. This scarcity of treatment options has been the driving force behind the efforts of a group of Tuskegee University cancer researchers to come up with innovative approaches to combat this dreaded disease.
The team of Tuskegee University scientists, anchored by Timothy Turner and Clayton Yates, utilized an innovative strategy that both targets and kills prostate cancer cells by combining synthetically designed lytic peptides with a prostate cancer targeting entity, LHRH (luteinizing hormone releasing hormone) to ensure specificity. Because a majority of prostate cancer cells express receptors for LHRH, this makes for an excellent target site. Lytic peptides, a universally produced product of nearly all multi- and some single-cellular life forms, have been shown to have a variety of uses, including the ability to kill cancer cells. However, the major reoccurring drawback associated with using these naturally produced peptides as a cancer therapeutic has been their indiscriminant toxicity to both non-cancerous and cancerous cells.
Team member and expert small peptide design biochemist Jesse Jaynes has been able to overcome this problem by synthetically designing different variations of cancer destroying lytic peptides.
“Our ability to design novel peptides that are capable of destroying cancer in a targeted way will be useful in the development of new drugs to treat many different types of cancer” he said.
These creative designs help enhance the peptides’ ability to kill prostate cancer cells at low concentrations, while simultaneously being less toxic to normal cells. The research team added the targeting element to these peptides to make the resulting compounds specific for prostate cancer cells. Utilizing this new innovative approach, the team was able to evaluate by real-time video imaging the efficacy of these newly constructed peptides to inhibit cancer growth. In six hours time, the cancer cells started to burst and explode, resulting in approximately 100 percent cell death after 24 hours in the most aggressive types of prostate cancer cells.
The Tuskegee team believes that their findings will be translatable into in vivo models systems, and ultimately have clinical utility in the fight against prostate cancer.
“The ability to selectively target and kill cancer cells, while sparing the normal cells has the potential to limit the harsh number of side effects caused by existing chemotherapeutic drugs,” Yates said.
The mere fact that the low concentration and fast action of these compounds differ from other classical chemotherapeutic agents, gives hope that directed therapies such as these would enhance therapeutic options for prostate cancer patients suffering from advanced disease.
Turner reiterates the team’s desire: “We want to use everything at our disposal to change the landscape of prostate cancer treatment forever and to reduce the impact this disease causes on all people.”
In April, Tuskegee University President Gilbert L. Rochon signed a memorandum of understanding to collaborate with the Curtis D. Robinson Men’s Health Institute at St. Francis Hospital in Hartford, Conn. The two institutions will also join to create a faith-based outreach and educational marketing campaign about the disease, and study why prostate cancer has a disproportionately high death rate among black men.
The Tuskegee University biology department will receive tissue samples from prostate cancer surgeries, in support of their research on development of therapeutic interventions for prostate cancer. The collaboration will include scientific research and testing to determine how prostate cancer is passed on in black men and also predict which cancers will be more aggressive.
Part of this work was published in the January 2011 edition of the journal, “Biochemical Pharmacology.”
Clayton Yates, part of the Tuskegee research team, presents findings at a meeting for the university's collaboration with the Curtis D. Robinson Men's Health Institute and Saint Francis Hospital of Connecticut in April.