Epigallocatechin3gallate and simvastatin inhibit myeloma cancer cells proliferation by apoptosis and cell cycle arrest upregulation.

Abstract

Myeloma cancer (MC) is the second most common hematologic malignancy. It represents a clonal disorder of plasma B-cells arising in the bone marrow. Despite the wide advance in treatment options over recent years, the disease remains incurable. The current study was designed to evaluate Epigallocatechin3gallate (ECG) and simvastatin (SVN) anticancer effect on MC cells. MC cells were divided into the control, MC+ECG, MC+SVN, and MC+ECG+SVN groups. MC cells proliferation in all groups was evaluated using cell morphological status, qRT-PCR was used to analyze apoptotic gene expression, the cell cycle was examined using flowcytometry, and biochemical analysis of oxidative and antioxidant mediators was determined. The doses of ECG (100µmol/L) and SVN (0.1µmol/L) induced cytotoxicity in about 60% of myeloma cells. ECG induced apoptotic genes upregulation (P53, poly (ADP-ribose) polymerase 1 (PARP-1), B-cell leukemia/lymphoma 2 (Bcl-2)-associated protein x (Bax), and caspase-3), and anti-apoptotic gene downregulation (Bcl-2). Moreover, the current regimens have a potent effect on cancer cell growth through G2/M arrest, as observed Graphical abstract figure. The current regimens induced oxidative stress downregulation and antioxidant enzymes activity upregulation. In conclusion, both ECG and/or simvastatin caused MC cell toxicity. Nevertheless, the synergistic influence of ECG and simvastatin possesses a more potent consequence on minimizing the resistance of tumor cell and killing tumor cells.