The study built on earlier work by SDSU distinguished professor Chandradhar Dwivedi’s lab looking at the chemopreventive effects of sarcophine-diol, made from a substance called sarcophine that can be isolated from soft coral found in the Red Sea. The new study carried the work beyond looking at sarcophine-diol’s possible use in prevention of skin cancer to consider its potential as a tool in therapies to actually treat skin cancer.
“We are finding that sarcophine-diol could be used both for chemoprevention and as a chemotherapeutic agent,” Dwivedi said.
Specifically, the new SDSU research explored sarcophine-diol’s potential to inhibit cell growth of cancers, and also its potential to induce orderly, programmed cell death of skin cancer cells.
The scientists published their research findings in March 2009 in the academic journal Translational Oncology.
Dwivedi, head of SDSU’s Department of Pharmaceutical Sciences, directed the study by departmental graduate student researcher Xiaoying Zhang. Other researchers involved included Ajay Bommareddy of the University of Pittsburgh Cancer Institute, a former graduate student in Dwivedi’s laboratory; SDSU graduate student Wei Chen of the Department of Pharmaceutical Sciences; Sherief Khalifa of Misr International University in Cairo, Egypt; assistant professor Radhey Kaushik, who has a joint appointment in SDSU’s Department of Veterinary Sciences and the Department of Biology and Microbiology; and associate professor Hesham Fahmy of the SDSU Department of Pharmaceutical Sciences.
SDSU researchers found that treating human skin cancer cells with different concentrations of sarcophine-diol for different lengths of time reduced the viability of cancer cells in each case. Related work showed that sarcophine-diol also inhibited the proliferation or uncontrolled growth of cancer cells.
The SDSU study also showed that sarcophine-diol induced apoptosis, or programmed cell death, in cancer cells. The extent of apoptosis observed in different treatments in the study was correlated to the level of sarcophine-diol used, Dwivedi said.
However, sarcophine-diol did not induce what scientists call necrosis, or the premature death of healthy cells. Dwivedi said that is an important finding because it suggests sarcophine-diol could be used in treatments that specifically target cancer cells without damaging nearby healthy cells.
The SDSU experiment also looked at whether sarcophine-diol treatments could increase what is called DNA fragmentation, considered a biochemical hallmark of apoptosis — an indication that the cell is committed to die, in other words. At lower concentrations, sarcophine-diol didn’t significantly induce DNA fragmentation in skin tumor cells, but higher levels of sarcophine-diol did.
Finally, the SDSU study found that treatments with higher concentrations of sarcophine-diol induced higher level of so-called “executioner” proteins that have a role in apoptosis, or programmed cell death compared to a control group.
Importantly, the SDSU research found that sarcophine-diol did not significantly increase the level of the “executioner” proteins in normal cells. Sarcophine-diol had some effect on viability of healthy cells, but the results suggest sarcophine-diol is considerably more toxic to skin tumor cells than to healthy cells.
“Further investigations of sarcophine-diol in experimental models and in cell culture studies are needed to explore its mechanisms of action,” Dwivedi said. “Sarcophine-diol has excellent potential to be a potent chemotherapeutic agent that can be further investigated for use against nonmelanoma skin cancer development.”