Written by Joyce Smith, BS. Research finds that increasing concentrations of selenium causes certain malignant mesothelioma tumors to proliferate and grow.
The incidence of mesothelioma is increasing in many parts of the world. Selenium, because of its antioxidant properties, could be a potential candidate for the prevention and treatment of a variety of cancers [1]. However, the evidence is inconsistent and controversial [2]. One study has shown that extremely high levels of selenium can inhibit the growth of a particular cell line of malignant mesothelioma (MM) in a dose dependent manner [3] while some forms of selenium have actually promoted tumor growth [4]. This discrepancy highlights the need for science to identify the ways in which selenium influences the development of various cancers. Thus the objective of this study was to explore and evaluate the role that selenium plays in the development and progression of MM cell lines both in vivo and in vitro.
In Vitro:
Researchers established that certain MM cell lines are sensitive to selenium while others are not. They grew, in duplicate, four different MM cell lines (EKKH5, CRH5, AB12, and AK7) in culture media containing 30, 50 and 80 nmol/L selenium for 1 week. They found that proliferation and mobility increased with increasing concentrations for EKKH5 and CRH5 cell lines but not for AB12 and AK7. (P<0.05).
They next identified a signaling pathway affected in the selenium-sensitive versus the selenium-insensitive MM cell lines. When comparing the 4 cell lines they found that ERK, a signaling pathway involved in cell proliferation and mobility, is activated with increasing levels of selenium in the CRH5 and EKKH5 MM cell lines but not in AK7 or AB12, thus suggesting that ERK activation occurs only in selenium- sensitive MM cells. This validates a recent study showing that ERK activation is necessary for the growth of MM tumors [5].
By treating all 4 cell lines with the reducing agent N-acetyl cysteine (NAC), researchers found that all 4 cell lines proliferated equally regardless of selenium levels (P<0.05) thus demonstrating that the reducing capacity of selenium -sensitive cells is crucial to their proliferation and mobility.
In Vivo:
Mice were fed diets containing low (0.08 ppm), medium (0.25ppm) and high (1.0 ppm) selenium as sodium selenite for 4 weeks and then injected with CRH5 or AB12 cells. Tumor volume was measured weekly.
CRH5 cells were also injected into mice receiving only drinking water containing 0.4 mmol/L of the reducing agent N-acetyl cysteine (NAC) for the reminder of the experiment. These mice were sacrificed when tumors were large and life-threatening. Each experiment was duplicated.
Researchers found that increasing doses of selenium in vivo promoted proliferation and motility for CRH5 but not AB12 MM cell lines (P<0.05).
When these 2 cell lines were treated with the reducing agent NAC, the ability of selenium to activate ERK and support cell proliferation and mobility was eliminated. Thus MM tumor progression is dependent on the reducing capacity of selenium –sensitive MM cells. (P<0.05)
Conclusion:
The researchers conclude that certain MM tumors proliferate and spread with increasing concentrations of selenium because of selenium’s ability to increase the reducing capacity of selenium-sensitive MM cells. Therefore, researchers suggest, based on their data, that “increasing dietary selenium to benefit MM patients may be a counterproductive endeavor.
Source: Robinson, Cleo, et al. “Effect of NSAIDS and COX-2 inhibitors on the incidence and severity of asbestos-induced malignant mesothelioma: evidence from an animal model and a human cohort.” Lung Cancer 86.1 (2014): 29-34.
© 2017 Elsevier B.V. or its licensors or contributors.
Posted December 21, 2015.
References:
- Etminan, M., et al., Intake of Selenium in the Prevention of Prostate Cancer: a Systematic Review and Meta-analysis*. Cancer Causes & Control, 2005. 16(9): p. 1125-1131.
- Klein, E.A., et al., Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Jama, 2011. 306(14): p. 1549-1556.
- Apostolou, S., et al., Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype. Oncogene, 2004. 23(29): p. 5032-5040.
- Yoo, M.-H., et al., Selenoproteins harboring a split personality in both preventing and promoting cancer, in Selenium. 2012, Springer. p. 325-333.
- Shukla, A., et al., ERK2 is essential for the growth of human epithelioid malignant mesotheliomas. International Journal of Cancer, 2011. 129(5): p. 1075-1086.
