Potential new therapeutic molecular target to fight cancer

November 1, 2007

Researchers at the Virginia Commonwealth University Massey Cancer Center have identified the enzyme sphingosine kinase 2 as a possible new therapeutic target to improve the efficacy of chemotherapy for colon and breast cancer.

In the Nov. 1 issue of the journal Cancer Research, researchers examined human colon and breast cancer cells and established a role of sphingosine kinase 2 (SphK2), an enzyme that forms the potent lipid mediator sphingosine-1-phosphate in the death of cancer cells mediated by the chemotherapeutic drug, doxorubicin.

Doxorubicin is able to kill cancer cells by working with p53, one of the most protective anti-cancer proteins in the human body. However, doxorubicin also relies on p53- independent mechanisms to induce death in colon and breast cancer cells.

“Understanding how doxorubicin kills in a p53-independent manner is a major goal of cancer researchers because most cancer cells have mutated p53,” said lead author Sarah Spiegel, Ph.D., chair and professor in the VCU Department of Biochemistry and Molecular Biology and co-leader of the cancer center's cancer cell biology program.

According to Spiegel, the study demonstrated that SphK2 is important for p53-independent induction of expression of p21, a cyclin-dependent kinase inhibitor. This p21 regulates the cell cycle, and apoptosis or programmed cell suicide, mediated by doxorubicin. Human colon and breast cancer cells were killed more efficiently by doxorubicin when SphK2 was removed from the cells.

“Therefore, the findings suggest that SphK2 influences the balance between cytostasis, and apoptosis of human cancer cells,” Spiegel said. Cytostasis refers to the stoppage of cellular growth and multiplication.

Spiegel said that cell death was induced by doxorubicin and decreased p21.

Spiegel, who is internationally recognized for her pioneering work on new lipid mediators that regulate cell growth and cell death, and her colleagues, first discovered the role of sphingosine-1-phosphate in cell growth regulation nearly a decade ago. Spiegel and her team are continuing this work to better understand the functions of these enzymes.

Source: Virginia Commonwealth University

Explore further: Colorful potatoes may pack powerful cancer prevention punch

Related Stories

Cell mechanics are more complex than previously thought

August 27, 2015

Cell mechanics are considerably more complex than previously thought and may affect cell structures at various levels. This finding is based on a collaborative research project conducted by an international research team ...

Reprogramming the oocyte

August 26, 2015

(Phys.org)—Among other things, the egg is optimized to process the sperm genome. The cytoplasmic factors that make this possible also give the egg the ability to reprogram the nuclei from other kinds of cells if these nuclei ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.