Some chemotherapeutics-treated colon cancer cells display a specific phenotype being a combination of stem-like and senescent cell features.

Colorectal cancer (CRC) is the second leading cause of death among cancer patients in the Northern countries. CRC can reappear a long time after treatment. Recent clinical studies demonstrated that, in response to chemotherapy, cancer cells may undergo stress-induced premature senescence (SIPS), which typically results in growth arrest. Nonetheless, these senescent cells were reported to divide in an atypical manner and thus contribute to cancer re-growth. Therefore, we examined if SIPS escape may follow treatment with chemotherapeutics used clinically: 5-fluorouracil (5-FU), oxaliplatin (OXA) and irinotecan (IRINO). To mimic the therapeutic regimes we exposed human colon cancer HCT116 and SW480 cells to repeated cycles of drug treatment. The cells treated with 5-FU or IRINO exhibited several hallmarks of SIPS: growth arrest, increased size and granularity, polyploidization, augmented activity of the SA-ß-galactosidase, accumulation of P21 and CYCLIN D1 proteins, and the senescence-associated secretory phenotype. Moreover, re-population of the cancer cell cultures was delayed upon treatment with the senescence-inducing agents. At the same time, we detected a subpopulation of senescent colon cancer cells with features of stemness: elevated NANOG expression, exclusion of Hoechst 33342 (typical for side population) and increased CD24 expression. Additionally, rare, polyploid cells exhibited blastocyst-like morphology and produced progeny. In parallel, majority of chemotherapeutics-treated cells underwent mesenchymal to epithelial transition, as the percentage of CD44-positve cells was reduced, and levels of E-cadherin (epithelial marker) were elevated. Our study demonstrates that a subpopulation of chemotherapeutics-treated colon cancer cells display a specific phenotype being a combination of stem-like and senescent cell features. This may contribute to their resistance to chemotherapy and their ability to re-grow cancer after completion of therapeutic intervention.

Determination of some micro- and macroelements in preparations made from peppermint and nettle leaves.

As, Ca, Cd, Cu, Fe, Mg, Mn, Pb and Zn were determined by ICP-MS and ET-AAS in preparations made from peppermint and nettle leaves after microwave high pressure digestion with nitric acid. In preparation from nettle leaves the Ca content was more than three times higher than in preparations made from peppermint leaves. Only very small differences (less than 10%) were observed for all the other elements. In all the samples investigated the content of inorganic elements were below the WHO limit (where existing). Variation coefficients ranged from 0.68% to 10.5% for ICP-MS measurements and from 1.48% to 10.0% for ET-ASS.