Inhibitory effects of caffeic acid phenethyl ester (CAPE) derivatives on multiple myeloma cell growth

Location

Suwanee, GA

Start Date

14-5-2019 1:00 PM

End Date

14-5-2019 4:00 PM

Description

Multiple myeloma (MM) is a rare blood cancer that affects thousands of people yearly in the U.S. It stems from monoclonal plasma cells and can cause symptoms such as bone loss and fatigue. Recent studies have shown that the bone marrow microenvironment may mediate the tumor proliferation, drug resistance, and migration of the MM cells. Caffeic acid phenethyl ester (CAPE) has been studied due to its anti-cancer and anti-inflammatory effects. The objective of this study is to examine the inhibitory effects of CAPE derivatives on MM cell growth and explore structure activity relationship of CAPE. Methods: Seven CAPE derivatives were selected and tested on the growth of MM RPMI 8226 cells with a dose range from 1.0 to 50 µM within 72 hours. Most potent derivative was selected to further study whether its inhibitory effect on MM cell growth is due to induction of apoptosis through flow cytometric analysis. In addition, western blotting was used to determine protein expression of apoptosis-related factors including caspase 3 and poly-(ADP-ribose) polymerase (PARP). To evaluate the anti-myeloma effect of CAPE derivative in the presence of tumor microenvironment, a Transwell (TW) model using MM 8226 cells co-culturing with human bone marrow stromal HS5 cells was applied to mimic the bone marrow microenvironment in vivo. Results Cytotoxicity results show that FCAPE (a novel fluorinated CAPE), P4MC (phenylethyl-4-methylcaffeate), and NOC (N-octyl caffeate) decreased cell viability of MM 8226 cells in a dose and time-dependent manner with FCAPE being the most potent one. Apoptosis results show that FCAPE induces apoptosis of MM 8226 cells in a dose dependent manner within 24 hours and activates caspase 3 along with breakdown of PARP. TW model results show that FCAPE induces apoptosis of MM 8226 cells in the presence of HS5 co-culture. Conclusions: CAPE derivatives inhibit the growth of MM cells through induction of apoptosis, and this effect of CAPE requires integrity of the phenol group and presence of lipophilic ester group. FCAPE, the most potent derivative, exerts similar apoptogenic effect on MM cells culturing with TW model.

Embargo Period

1-28-2020

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May 14th, 1:00 PM May 14th, 4:00 PM

Inhibitory effects of caffeic acid phenethyl ester (CAPE) derivatives on multiple myeloma cell growth

Suwanee, GA

Multiple myeloma (MM) is a rare blood cancer that affects thousands of people yearly in the U.S. It stems from monoclonal plasma cells and can cause symptoms such as bone loss and fatigue. Recent studies have shown that the bone marrow microenvironment may mediate the tumor proliferation, drug resistance, and migration of the MM cells. Caffeic acid phenethyl ester (CAPE) has been studied due to its anti-cancer and anti-inflammatory effects. The objective of this study is to examine the inhibitory effects of CAPE derivatives on MM cell growth and explore structure activity relationship of CAPE. Methods: Seven CAPE derivatives were selected and tested on the growth of MM RPMI 8226 cells with a dose range from 1.0 to 50 µM within 72 hours. Most potent derivative was selected to further study whether its inhibitory effect on MM cell growth is due to induction of apoptosis through flow cytometric analysis. In addition, western blotting was used to determine protein expression of apoptosis-related factors including caspase 3 and poly-(ADP-ribose) polymerase (PARP). To evaluate the anti-myeloma effect of CAPE derivative in the presence of tumor microenvironment, a Transwell (TW) model using MM 8226 cells co-culturing with human bone marrow stromal HS5 cells was applied to mimic the bone marrow microenvironment in vivo. Results Cytotoxicity results show that FCAPE (a novel fluorinated CAPE), P4MC (phenylethyl-4-methylcaffeate), and NOC (N-octyl caffeate) decreased cell viability of MM 8226 cells in a dose and time-dependent manner with FCAPE being the most potent one. Apoptosis results show that FCAPE induces apoptosis of MM 8226 cells in a dose dependent manner within 24 hours and activates caspase 3 along with breakdown of PARP. TW model results show that FCAPE induces apoptosis of MM 8226 cells in the presence of HS5 co-culture. Conclusions: CAPE derivatives inhibit the growth of MM cells through induction of apoptosis, and this effect of CAPE requires integrity of the phenol group and presence of lipophilic ester group. FCAPE, the most potent derivative, exerts similar apoptogenic effect on MM cells culturing with TW model.