Teucrium polium induces apoptosis in peripheral blood lymphocytes isolated from human chronic lymphocytic leukemia
2019
Background/Aim. Chronic lymhocytic leukemia (CLL) is considered more as a
disease of cells accumulation due to the defect in apoptosis rather than
deregulated cell’s proliferation. The activation of apoptosis is one of the
main molecular mechanisms responsible for the anti-cancer activities of most
of the currently studied potential anti-cancer agents, including natural
compounds. Teucrium polium extracts exhibited strong cytotoxic effects in
murine leukemia cell line, RAW 264.7 and human melanoma cell line, C32, but
its cytotoxic effects against human leukemia cells were unknown. Methods. The
viability of human leukemia cell lines (MOLT-4 and JVM-13), CLL lymphocytes
isolated from 28 patients (CLL cells), and peripheral blood mononuclear cells
(PBMCs) isolated from 16 healthy subjects treated with Teucrium polium
extracts, was determined by MTT assay. Apoptosis of Teucrium polium treated
CLL cells was measured by flow cytometry applying Annexin V/7AAD staining.
The expressions of active proapoptotic protein Bax, antiapoptotic protein
Bcl-2, cytochrome c and the percentage of cells containing cleaved caspase-3
in treated CLL cells was determined by flow cytometry and
immunocytochemistry. Results. Teucrium polium methanol extract (TP) decreased
the viability of all tested human leukemia cells but it had no effect on the
viability of healthy PBMCs. The citotoxic effect of TP was caused by its
induction of CLL cells’ apoptosis. TP disarranged the ratio of the
expressions of proapoptotic Bax and antiapoptotic Bcl-2 protein in favor of
Bax, consequently inducing apoptosis by cytochrome c mitochondrial release
and activation of caspase-3 in treated CLL cells. Conclusion. Teucrium polium
induced selective apoptosis in CLL cells and it affected the expressions of
key proteins involved in the regulation of programmed cell death. [Project of
the Serbian Ministry of Education, Science and Technological Development,
Grant no. III41010]
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