Treatment with 2-methyl- 3-pentyl-6-methoxyprodiginine isolated from serracia marcescens decreases cell viability and induces appoptosis in acute lymphoblaastic leukemia cells

Acute lymphoblastic leukemia (ALL) is the most common malignancies in the world. Despite advances in treatment of patients with ALL, a subset of patients will have recurrent disease or refractory to chemotherapy and hematopoietic stem cell transplant. Consequently, assessment of the effectiveness of natural compounds with high efficacy and minimal side effects is warranted. In this regard, it has been shown that some of bacterial pigments such as prodigiosin isolated from cell wall of Serratia marcescens have dramatic anti-cancer activities. The aim of this study was to evaluate the effects of prodigiosin on the cell viability and cell number, cell proliferation and apoptosis in CCRF-CEM cell line that serves as a model for ALL cells.
Malignant cells were treated with 100, 200 and 400 nM prodigiosin for 24, 48 and 72 h and cell proliferation-rates were measured by performing WST-1 assay. Furthermore, malignant cells were treated with the indicated concentrations of prodigiosin for 48 h and cell viabilities and cell numbers along with apoptotic-rates were determined by trypan blue staining method and flow cytometer respectively.
Treatment of cells with increasing concentrations of prodigiosin significantly decreased Proliferation-rates in a dose- and time-dependent manner compared to untreated cells. Specifically, after 72 h treatments with 100, 200 and 400 nM prodigiosin, proliferation-rates were measured to be%77.3 ± %1.5, %63 ± %2, and%46.3 ± %3.2 respectively as compared to untreated cells. Furthermore, following 48 h treatments with indicated concentrations of prodigiosin, the cell numbers and viabilities were decreased in a dose-dependent manner. Specifically, treatment with 400 nM prodigiosin resulted in 44% (4.5 × 105 cells) and 63% for cell number and viability respectively as compared to untreated cells. At the same conditions, apoptotic-rates (Early Late) were measured to be 33.8% to 72.8% at the indicated prodigiosin concentrations ranging.
Prodigiosin decreased cell number and viability as well as cell proliferation-rates. This compound also increased apoptosis in CCRF-CEM cells. Therefore, this compound with high pro-apoptotic capacity represents an attractive anti-leukemic agent in ALL.