Discovery of a protein that causes racial differences in prostate cancer

The prostate is a male-specific gonad. The prostate is as big as a chestnut, with its bottom facing up to the bladder and the sharp point pointing downwards to the urogenital ridge. It secretes prostatic fluid, which is an important component of semen. And semen plays an important role in the normal function of sperm and is very important for fertility. The secretion of prostatic fluid is regulated by androgen. The prostate can also control urination. All in all, it is an important organ for males.

Because the only man has the prostate, prostate cancer is a male-only disease. And it is the second most common male cancer in the United States, after skin cancer. The disease is most common in men over the age of 65 and rarely occurs in people under 40. 

Cancer researchers have long known that prostate cancer tends to be more common, aggressive and resistant to existing treatments in African Americans than in Caucasian-Americans, but now they are only beginning to understand why. 

A study conducted by Dhyan Chandra, Ph.D. showed that mitochondrial dysfunction and the inability to produce apoptosome are key factors in the high incidence and poor prognosis of African American prostate cancer. And the researchers also proposed strategic goals to overcome these factors with new therapies. These findings were published in Cancer Research, a journal of the American Association for Cancer Research (AACR).  

The researchers found that many African Americans lack a key mitochondrial protein called cytochrome c, which is an electron carrier protein. Cytochrome c is a component of the electron transport chain in mitochondria. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. 

Cytochrome c is also involved in the initiation of apoptosis. Upon release of cytochrome c to the cytoplasm, the protein binds apoptotic protease activating factor which activates the apoptotic initiator procaspase 9. In a word, cytochrome c is a major protein that promotes the formation of the ideal "death wheel" effect against cancer cells.

Generally, cytochrome c deficiency can occur in people of any race or background but is common in people of African Americans. Cancer promoters such as c-Myc and NF-κB are often overexpressed in African American men, ultimately inhibiting the production of cytochrome c. 

Their findings uncovered why the current class of drugs used to treat first-line prostate cancer, primarily docetaxel, do not benefit many African American men. Docetaxel, an anti-tumor agent, acts by interfering with microtubule networks necessary for mitotic and intermitotic cell function. And mitochondria are the energy stations that power the life of a cell.  Importantly, however, these findings also provided strong evidence that new therapeutic strategies can be developed to address and exploit these mechanisms.

The team made sure that suppressing the cancer-promoting proteins c-Myc and NF-κB can restore cytochrome c in prostate cancer cells with a lack of cytochrome c, thereby increasing the production of apoptosome to kill those cells.

Following, the researchers plan to conduct clinical trials to evaluate the effectiveness of the treatment for prostate cancer by inhibiting c-Myc and NF-κB with existing drugs approved for other applications.