The activity of Selol in multidrug-resistant and sensitive human leukemia cells

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The activity of Selol in multidrug-resistant and sensitive human leukemia cells.

Authors: Piotr Suchocki, Irena Misiewicz, Katarzyna Skupinska, Karolina

Waclawek, Zbigniew Fijalek, Kasprzycka-Guttman

Affiliations: National Medicine Institute, 00-725 Warsaw, Poland

Pages: 893-899

Abstract: Selol is a mixture of selenitetriglycerides synthesized from

sunflower oil. As it contains the element selenium in its structure, it is

suspected to exhibit chemopreventive and anticancer activity. In this study,

the ability of Selol to inhibit cell proliferation and to induce apoptosis

was investigated. Three cell lines were used: leukemia HL-60 cell line and

multidrug-resistant HL-60/Dox (resistant to doxorubicin) and HL-60/Vinc

(resistant to vincristine). Selol was shown to reduce the cell number as a

result of treatment with increasing concentrations. For selected

concentrations the evidence of apoptosis (changes in mitochondrial potential

and caspase activity) was investigated, as well as changes in lysosome

distribution. The study has shown that Selol overcame the cell resistance,

as doxorubicin-resistant cells were more sensitive towards Selol than

sensitive cells.

...In single-dose toxicity studies performed in rats, LD50 was 100 mg Se/kg

after oral administration of Selol. The subcutaneous and intraperitoneal

administration of Selol showed extremely low toxicity, therefore precise

determination was impossible. Selol did not show a cumulative toxicity (11).

Selol did not show mutagenicity which was proven with Salmonella strains.

Selol's low toxicity, contrary to other selenium compounds, make

administration of higher

doses of selenium possible, which may lead to a more potent anti-cancer

activity.

....Summarizing, our study revealed cell growth inhibition in all cell lines,

which suggests that Selol can be a promising anticancer agent. Moreover, the

activity was stronger in the resistant cells, which suggests that it can

overcome cell resistance to anticancer drugs and could be used as a

chemosensitizing agent. It is clear that much additional research will be

required before a complete understanding of the anticancer mechanism of

Selol will be reached.

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Jan