Alpha Particles Induce Autophagy in Multiple Myeloma Cells
#MMPMID26539436
Gorin JB
; Gouard S
; Ménager J
; Morgenstern A
; Bruchertseifer F
; Faivre-Chauvet A
; Guilloux Y
; Chérel M
; Davodeau F
; Gaschet J
Front Med (Lausanne)
2015[]; 2
(?): 74
PMID26539436
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OBJECTIVES: Radiation emitted by the radionuclides in radioimmunotherapy (RIT)
approaches induce direct killing of the targeted cells as well as indirect
killing through the bystander effect. Our research group is dedicated to the
development of ?-RIT, i.e., RIT using ?-particles especially for the treatment of
multiple myeloma (MM). ?-irradiation and ?-irradiation have been shown to trigger
apoptosis in tumor cells. Cell death mode induced by (213)Bi ?-irradiation
appears more controversial. We therefore decided to investigate the effects of
(213)Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor
cell immunogenicity after irradiation. METHODS: Murine 5T33 and human LP-1 MM
cell lines were used to study the effects of such ?-particles. We first examined
the effects of (213)Bi on proliferation rate, double-strand DNA breaks, cell
cycle, and cell death. Then, we investigated autophagy after (213)Bi irradiation.
Finally, a coculture of dendritic cells (DCs) with irradiated tumor cells or
their culture media was performed to test whether it would induce DC activation.
RESULTS: We showed that (213)Bi induces DNA double-strand breaks, cell cycle
arrest, and autophagy in both cell lines, but we detected only slight levels of
early apoptosis within the 120?h following irradiation in 5T33 and LP-1.
Inhibition of autophagy prevented (213)Bi-induced inhibition of proliferation in
LP-1 suggesting that this mechanism is involved in cell death after irradiation.
We then assessed the immunogenicity of irradiated cells and found that irradiated
LP-1 can activate DC through the secretion of soluble factor(s); however, no
increase in membrane or extracellular expression of danger-associated molecular
patterns was observed after irradiation. CONCLUSION: This study demonstrates that
(213)Bi induces mainly necrosis in MM cells, low levels of apoptosis, and
autophagy that might be involved in tumor cell death.
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