Potential new therapeutic molecular target to fight cancer

Nov 01, 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: Study identifies enzymes that help fix cancer-causing DNA defects

add to favorites email to friend print save as pdf

Related Stories

Researchers develop new model of cellular movement

Apr 18, 2014

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

Physicists create new nanoparticle for cancer therapy

Apr 16, 2014

A University of Texas at Arlington physicist working to create a luminescent nanoparticle to use in security-related radiation detection may have instead happened upon an advance in photodynamic cancer therapy.

Recommended for you

Cancer patients need anxiety, depression screening

12 hours ago

(HealthDay)—It is important to recognize and treat anxiety or depression among cancer patients, according to a clinical guideline published online April 14 in the Journal of Clinical Oncology.

Pre-HPV vaccine, most oropharyngeal cancers HPV+

13 hours ago

(HealthDay)—Most oropharyngeal cancers in the United States diagnosed between 1995 and 2005 were positive for human papillomavirus (HPV), specifically HPV 16 or 18, according to a study published in the May issue of the ...

User comments : 0

More news stories

Computer screening could help patients and healthcare

A trial of a new patient care model, which uses over-the-phone consultations and computers to help better understand the needs of the patient, has begun this week, led by researchers at the University of Adelaide.

In the 'slime jungle' height matters

(Phys.org) —In communities of microbes, akin to 'slime jungles', cells evolve not just to grow faster than their rivals but also to push themselves to the surface of colonies where they gain the best access ...

Robot scouts rooms people can't enter

(Phys.org) —Firefighters, police officers and military personnel are often required to enter rooms with little information about what dangers might lie behind the door. A group of engineering students at ...

New alfalfa variety resists ravenous local pest

(Phys.org) —Cornell plant breeders have released a new alfalfa variety with some resistance against the alfalfa snout beetle, which has ravaged alfalfa fields in nine northern New York counties and across ...