Caffeic Acid Markedly Induced Apoptosis of Human Multiple Myeloma Cells through the Caspase-dependent Pathway

Abstract

Background Caffeic acid (CA) or 3,4-dihydroxycinnamic acid is a polyphenolic compound primarily found in coffee, herbs, berries, and other fruits. Its antioxidant, anti-inflammatory, and immunomodulatory effects on multiple health conditions have been evaluated and reported. CA’s anti-tumor effect has been reported in solid tumors, but evidence regarding liquid tumors such as multiple myeloma (MM) is limited. The increasing incidence of MM globally provides a justified rationale to explore the potential of CA on human MM cells through caspase-dependent induced apoptosis. Objectives The study explores CA’s therapeutic effect and mechanism on multiple myeloma. Materials and Methods We performed flow cytometry at different concentrations and time points after treating human MM cell lines (MM.1R, RPMI8226, and U266) with CA to identify apoptosis and changes in mitochondrial membrane potential. A Western blot was used to assess the expression of an apoptosis-related protein in MM cell lines. Statistical Analysis Used Student’s t-test was used to evaluate the mean difference between the experimental group and the control group. Results CA markedly induced the apoptosis of MM cells in a dose- and time-dependent manner. After co-incubation with CA, JC-1 (a cationic lipid fluorescent dye was used as an indicator of mitochondrial transmembrane potential), flow cytometry results showed that the mitochondrial membrane potential of MM cells significantly decreased, and the Western blot showed activation and cleavage of caspase-3, which is the classical marker of the mitochondrial apoptosis pathway. The experimental group was statistically significant compared with the control group (p < 0.01). Conclusion Our research demonstrated that CA induced MM cell apoptosis through disturbing mitochondrial membrane integrity, followed by caspase-3 splitting, and suggested that CA might have tremendous therapeutic potential for MM treatment.