Effectiveness of sulforaphane as a radiosensitizer for murine osteosarcoma cells

Abstract

Sulforaphane (SFN), a naturally occurring member of the isothiocyanate family, is effective against various types of malignant tumor cells. We studied whether the combination of SFN and radiation would be more effective against osteosarcoma cells when compared to these treatments alone. LM8 murine osteosarcoma cells were cultured with various concentrations of SFN for 24 h and/or 2 Gy X-irradiation. The effects of individual and combination treatments on the number of cells, the cell cycle, cell proliferation-related factors and apoptosis were analyzed. The combination of SFN plus radiation had significantly greater antitumor effects than either treatment alone. Exposure to SFN increased the population of cells in the G2/M phase. Combination treatment resulted in a higher percentage of cells being in sub-G1 than did SFN alone. In addition, the combination of SFN and radiation effectively induced nuclear fragmentation and apoptotic bodies, as shown by DAPI staining. The combination of SFN and 2 Gy radiation increased the cleavage and activation of caspase-3 compared with SFN or radiation alone, as shown by western blotting. Although radiation alone increased the phosphorylation of ERK and Akt proteins, the combination of SFN and radiation induced suppression of ERK and Akt phosphorylation when compared with radiation alone. We found that SFN enhanced the radiosensitivity of LM8 murine osteosarcoma cells by inducing apoptosis through G2/M-phase arrest and by inhibiting ERK and Akt activation. These findings suggest that SFN can be used as a radiosensitizer for osteosarcomas.

Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy

“…The combination of SFN and 2 Gy of radiation suppressed ERK and AKT phosphorylation. It was also discovered that SFN induced apoptosis through G2/M phase arrest and inhibited the activation of ERK and AKT [63] (Fig. 5).…”

“…Loss of viability was evident by increased formation of micronuclei and apoptotic bodies [64]. SFN may prove to be a promising molecular targeting chemotherapeutic agent for OS cancers [63]. …”

Mechanisms of the Anticancer Effects of Isothiocyanates

“…Additionally, the combination of radiation therapy with BITC inhibited NFκB and activated p38. The combination of BITC or SFN with radiation therapy augmented the radiation induced G2/M arrest [19,139]. Combination of SFN with radiation therapy led to inhibition of AKT, ERK, and MCL-1, explaining its efficacy [139,[152][153][154][155].…”

“…The combination of BITC or SFN with radiation therapy augmented the radiation induced G2/M arrest [19,139]. Combination of SFN with radiation therapy led to inhibition of AKT, ERK, and MCL-1, explaining its efficacy [139,[152][153][154][155]. TNF-related apoptosis inducing ligand (TRAIL) has been utilized as potential chemotherapeutic agent due to overexpression of TRAIL death receptor in cancer cells.…”

“…Due to its wide range of cellular targets, ITCs can be utilized for combinatorial therapeutic approaches. Combination of ITCs with conventional chemotherapeutic agents has been tested in preclinical models [19,[139][140][141].…”