Treatment with 2-methyl- 3-pentyl-6-methoxyprodiginine isolated from Serratia marcescens decreases cell viability and induces appoptosis in acute lymphoblastic 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.
Materials & Methods: Malignant cells were treated with 100, 200 and 400 nM prodigiosinfor 24, 48 and 72 h and cell proliferationrates 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.
Results: 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.
Conclusion: 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.