A synthetic version of a compound found in turmeric, called curcumin, has shown success in slowing and even stopping the growth of prostate cancer cells in the laboratory. This synthetic compound, dubbed ca27, harnesses the anti-cancer potential of curcumin in such a way that it is effective in the body, unlike natural curcumin, which is not readily absorbed.
Recent research by UNM Cancer Center scientists and their colleagues, published in the journal The Prostate, provides new evidence for the therapeutic potential of this novel turmeric-derived compound and comes closer to uncovering how the compound works. The study points the way to potential new treatment strategies for advanced prostate cancer.
Aside from skin cancer, prostate cancer is the most common cancer in American men, and is the second most deadly, behind lung cancer.
In 2011, it is estimated that 240,890 new cases of prostate cancer will be diagnosed in the U.S., and 33,720 men will die from the disease. About 1,312 of those cases will occur in New Mexico and 199 men in the state are projected to die from prostate cancer. In addition, the psychological and economic impact of the disease is enormous. However, there are more than 2 million American men currently living who have at some point been diagnosed with prostate cancer, and five year survivorship rates for early-stage prostate cancers are very high.
Though many prostate cancers are slow-growing and remain confined to the prostate for a long time, others are more aggressive and can spread beyond the prostate. Men with more aggressive prostate cancers may be treated with androgen ablation therapy, which lowers the amount of androgen in the body. Androgens are compounds that help regulate male characteristics and include familiar hormones like testosterone.
The androgen receptor (AR) is the hormone receptor that works with androgens; it influences the development and functioning of the prostate but also plays a key role in the rise and progression of prostate cancer. Androgen ablation therapy seeks to slow prostate cancer growth by reducing androgen levels to put a "brake" on the AR.
Though this therapy can be effective in some cases, certain patients develop so-called "androgen ablation-resistant prostate cancer" after 12-18 months. In these patients, the AR continues to promote prostate cancer growth even in the absence of androgen. In response, researchers have sought to develop treatments that reduce AR expression directly, regardless of androgen levels. This is where curcumin comes into the story.
Curcumin’s Therapeutic Potential
Curcumin is a naturally occurring substance which has been shown to inhibit the functions of AR proteins. However, it also has very low bioavailability, meaning it is hard for the body to absorb.
Recognizing the promise of curcumin, scientists created a collection of slightly altered and more easily taken-in curcumin analogs in an effort to increase its therapeutic utility. In the UNM study, researchers selected one of these synthetic curcumins, ca27, and investigated its ability to down-regulate, or diminish, AR protein expression and activity, potentially inhibiting the growth of prostate cancer cells.
In order to find out what kind of impact ca27 has on prostate cancer cells, the UNM researchers combined various concentrations of ca27 with several lines of cultured prostate cancer cells in the laboratory. While unaltered curcumin had no down-regulation effect on the prostate cancer cells, ca27 did. Not only did ca27 stop the growth of prostate cancer cells, it also caused some of them to lose viability.
Furthermore, in an exciting step towards understanding how ca27 has this effect, researchers believe they have found evidence that points towards increased cellular oxidative stress as the mechanism that down-regulates the AR protein and can trigger cancer cell death.
Oxidative stress occurs when cells experience an increase in reactive oxygen species (ROS), highly reactive molecules containing oxygen. The reactive nature of the molecules, caused by unpaired outer electrons, can cause cellular damage which eventually leads to oxidative stress and the death of the cell.
In future studies, the UNM team hopes to confirm whether and how ca27, and other curcumin analogs, incite oxidative stress in prostate cancer cells. This will lay the groundwork for developing more effective therapies which act directly on inhibiting AR expression (rather than modulating androgen production) and thereby offer new hope for men with androgen ablationresistant prostate cancer and other advanced forms of the disease.
"The curcumin analog ca27 down-regulates androgen receptor through an oxidative stress mediated mechanism in human prostate cancer cells" was first published in The Prostate’s online edition July 27, 2011. Authors include Alexandra M. Fajardo (UNM Cancer Center, Biochemistry and Molecular Biology, Pharmaceutical Sciences), Debra A. MacKenzie (UNM, Pharmaceutical Sciences), Ming Ji (UNM, Biochemistry and Molecular Biology), Lorraine M. Deck (UNM, Chemistry and Chemical Biology), David L. Vander Jagt (UNM Cancer Center, Biochemistry and Molecular Biology), Todd A. Thompson (UNM Cancer Center, Pharmaceutical Sciences), and Marco Bisoffi (UNM Cancer Center, Biochemistry and Molecular Biology).