Evaluation of Cytotoxicity, Cell-Cycle Arrest, and Apoptotic Induction of Three Ruellia tuberosa Leaf Extracts in MCF-7 Cells

Abstract

This study investigated the mechanisms responsible for the antiproliferative activities of three Ruellia tuberosa (RT) leaf extracts against MCF-7 cells after liquid-liquid partitioning. Among these extracts, methanol leaf extract exhibited the greatest inhibition of cell growth compared to water and hexane extracts. Results from JC-1 staining and apoptosis assay demonstrated that these leaf extracts induced apoptosis via caspase or mitochondrial independent manner as only substantial apoptotic cells with no obvious loss of mitochondrial membrane potential were found. However, the decrease in the BCL-2/BAX ratio is due to upregulated BAX expression, implying cells undergoing apoptosis. The expression of caspase 9 was unaltered except for cells treated with hexane leaf extract. Additionally, perturbation of cell cycle progression mainly at G1 or S phases was noticeable in treated cells and concentration-dependent. The distinct effect of different leaf extracts on the cell cycle was also reflected by the dysregulation of cyclins (A2 or E1) and cyclin-dependent kinase (CDK6). These findings have unveiled the therapeutical value of RT leaf extracts in breast cancer.

GRAPHICAL ABSTRACT

Key words:

• Breast cancer
• Apoptosis
• Cell cycle
• Ruellia tuberosa