The potential anti tumor activity of a herbal extract against cancer stem cells in Egyptian leukemic patients

Abstract

CSCs are a population of cells with stem cell-like properties that are considered to be the major cause of tumor heterogeneity, because of their ability to generate the full repertoire of cancer cell types. In addition, CSCs have been invoked as the main drivers of metastatic dissemination and therapeutic resistance. CSCs, including LSCs are minor subpopulations of cells with enormous proliferative potential. They possess a great role in the incidence, metastasis and relapse of the tumor, in addition to their involvement in drug resistance. So, targeting these CSCs may provide insights into the development of prognostic markers and specific therapeutic interventions. The present study aimed to determine the cytotoxic and apoptotic effects of aqueous-ethanol extract of L. cylindrica leaves on ALL blasts as well as LSCs. In the present study, thirty two bone marrow samples of newly diagnosed ALL patients were assayed for the expression of CD34+/CD38+ and CD34+/CD38- cells before and after treatment with L. cylindrica leaves extract by flow cytometry. Cell viability after treatment was measured by MTT assay. Cell cycle, apoptosis, proliferation marker Ki-67 and colony formation assay were further analyzed in this study. Morphological apoptotic changes induced in the bone marrow aspirate of ALL patients after treatment with the aqueous-ethanol extract of L. cylindrica leaves through microscopic examination were evaluated. The results showed the cytotoxic effect of L. cylindrica leaves extract against CD34+/CD38- and CD34+/CD38+ LSCs. L. cylindrica leaves extract displayed marked inhibition of proliferation, induction of apoptosis, arrest of cell cycle and suppression of colony formation in cultured ALL cells. The results of the present study also showed a significant apoptotic effect induced by L. cylindrica leaves extract on the blast cells, as detected by the marked apoptotic changes on the morphology of all treated bone marrow films. Additionally, the percentages of extract-induced apoptotic activity for blast cells were shown to be higher than for lymphocytes. These findings confirmed the potent cytotoxic activity of L. cylindrica leaves extract that targeting mainly the tumor cells.