Title

Anti-myeloma Effects of Xanthohumol on Human Multiple Myeloma Cells in Vitro via Induction of Apoptosis and Activation of AMPK Pathway

Date of Award

5-2020

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Xinyu Wang, PhD

Second Advisor

Harold Komiskey, PhD

Third Advisor

Srujana Rayalam, DVM, PhD

Fourth Advisor

Richard White, PhD

Abstract

Multiple myeloma (MM) is characterized as a type of white blood cell cancer, specifically affecting plasma cells within bone marrow, resulting in approximately 13,000 deaths each year in the United States (1). The over-accumulation of malignant plasma cells crowds out normal, healthy blood and immune cells, leaving the host potentially immunocompromised and prone to weakness, fatigue, weight loss and broken bones (2). Not surprisingly, the bone microenvironment has been shown to mediate drug resistance and tumor proliferation. Xanthohumol (XN), a prenylated flavonoid derived from the common hop Humulus lupulus L, has been shown to have profound anti-obesity, anti-inflammatory and anti-cancer effects. However, its effect on MM was rarely evaluated. The purpose of our study was to examine the cytotoxic and apoptogenic effects of XN on human MM cells. Our results show that XN decreased viability of MM RPMI 8226 cells in a time (24, 48, 72 hours) and dose (1, 5, 10, 20 and 30 μM) -dependent manner. Apoptogenic effect of XN was confirmed by flow cytometry analysis and western blotting. Our data demonstrated that, as the concentration of XN administered increased, the number of apoptotic MM cells increased accordingly. Protein expression of apoptosis-related factors including caspase 3, caspase 8, caspase 9, poly-(ADP-ribose) polymerase (PARP) and AMPK was examined and showed that the amounts of cleaved caspase 3, PARP1 and AMPK were increased corresponding to an increase of XN concentrations. Lastly, to evaluate the effect of XN on RPMI 8226 MM cells in the presence of a simulated microenvironment model, a Transwell (TW) plate was employed through which the cell viability of MM cells co-cultured with human bone marrow stromal cells HS-5 was assessed after administration of XN. Apoptogenic effect of XN was again confirmed by flow cytometry analysis and western blotting. In conclusion, our data suggests that XN inhibits MM cell proliferation through induction of apoptosis and possibly AMPK activation in the presence of a bone marrow microenvironment.

This document is currently not available here.

Share

COinS