LGC and Barts investigate benefits of selenium in cancer treatment
10 Aug 2011
LGC and Barts Cancer Institute pioneer research into the benefits of selenium in combination cancer therapies
LGC, the UK’s National Measurement Institute for chemical and bioanalytical measurement, is collaborating with Barts Cancer Institute at St. Bartholomew’s Hospital (Barts), London to develop new methods to better understand the effects of selenium in cancer treatment. The research project reflects the increasing awareness amongst cancer researchers that selenium may be beneficial both in preventing cancer and in improving the efficacy of cancer therapies.
Selenium occurs in different chemical forms (species) which, depending on concentration and structural composition, vary in their nutritional value, biological effects and toxicity. In vitro studies using lymphoma cell lines have shown that low, non-toxic concentrations of methylseleninic acid (MSA), an organic selenium compound, can increase the efficacy of chemotherapeutic agents. In order to understand the mechanisms by which this occurs, a combination of data provided by mass spectrometry and biological measurements is required.
Described in two recently published papers,(1,2) LGC scientists and researchers from Barts Cancer Institute are using both high accuracy mass spectrometry procedures, such as LGC’s newly developed HPLC-APEX-Q-ICP-MS* method and novel electrochemiluminescence assays, to understand the mechanisms by which MSA increases the sensitivity of cancer cells to the effects of chemotherapeutic agents.
These research papers demonstrate, for the first time, the formation of intracellular dimethylselenide, a methylation product of methylselenol – an anticancer metabolite – which occurs more rapidly in lymphoma cells lines exposed to MSA compared to non-malignant cells. Using novel HPLC-APEX-Q-ICP-MS, LGC scientists demonstrated a 12-fold lower limit of detection for target selenium species than those obtained by conventional methods.
In addition, the research indicated that maximum uptake of selenium by lymphoma cells was reached much earlier than in non-malignant cell lines and that target selenium species were present in much higher concentrations in the ‘headspace’ above the lymphoma cells. These findings support the differences in the biological effects of non-toxic levels of selenium observed by the Barts Cancer Institute team, who have also shown that the selenium metabolites formed in cells can inhibit key enzymes implicated in lymphoma and other cancers.
Heidi Goenaga-Infante, LGC’s Principal Scientist in Mass Spectrometry commented: “This successful collaboration between LGC and Barts Cancer Institute has generated novel data that provides a better understanding of how selenium affects important biological pathways in cancer cells, information that will now be valuable in determining the best way to use selenium drugs to improve treatment outcome.”
Translation of the developed methods into the clinic is the next challenge and, if successful, the simple addition of selenium to standard chemotherapy could lead to more effective cancer treatment.
(1) Capabilities of HPLC with APEX-Q nebulisation ICP-MS and ESI MS/MS to compare selenium uptake and speciation of non-malignant with different B cell lymphoma lines, Goenaga-Infante H, Kassam S, Stokes E, Hopley C, Joel S, Anal. and Bioanal. Chem., Volume 399, Number 5, 1789-1797
(2) Methylseleninic acid inhibits HDAC activity in diffuse large B-cell lymphoma cell lines, Kassam S, Goenaga-Infante H, Maharaj L, Hiley CT, Juliger S, Joel SP, Cancer Chemother. Pharmacol. 2011 Apr 26, [Epub ahead of print]
* High performance liquid chromatography coupled to inductively coupled mass spectrometer via APEX-Q nebuliser