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MGDG extracted from spinach enhances the cytotoxicity of radiation in pancreatic cancer cells

View Article: PubMed Central - PubMed

ABSTRACT

Background: In our previous study, monogalactosyl diacylglycerol (MGDG) purified from spinach was found to have cytotoxic effects in human cancer cell lines. This study further assessed whether MGDG can enhance the cytotoxic effects of radiation in human pancreatic cancer cells in vitro and in vivo.

Methods: Glycoglycerolipids from spinach including MGDG were extracted from dried spinach. The cytotoxicity of MGDG were evaluated by the MTT assay using four human pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal human dermal fibroblasts (NHDFs). The effects of radiation and MGDG alone or in combination in MIAPaCa-2 cells was analyzed with the colony forming and apoptosis assays, western blotting and cell cycle and DNA damage analyses (γ-H2AX foci staining and comet assay). The inhibitory effects on tumor growth were assessed in a mouse xenograft tumor model.

Results: MGDG showed dose- and time-dependent cytotoxicity, with half-maximal inhibitory concentrations (IC50) in PANC-1, BxPC-3, MIAPaCa-2 and AsPC-1 cells at 72 h of 25.6 ± 2.5, 26.9 ± 1.3, 18.5 ± 1.7, and 22.7 ± 1.9 μM, respectively. The colony forming assay revealed fewer MIAPaCa-2, BxPC-3 and AsPC-1 cell colonies upon treatment with both MGDG and radiation as compared to irradiation alone (P < 0.05). The combination of MGDG and radiation induced a higher proportion of apoptosis in MIAPaCa-2 cells; this effect was associated with increased mitochondrial release of cytochrome c and activation of cleaved poly (ADP-ribose) polymerase and caspase-3. DNA damage was detected and DNA repair mechanisms were more frequently impaired in cells receiving the combination treatment as compared to either one alone. Tumor growth was inhibited to a greater degree in mice treated by intratumoral injection of MGDG combined with irradiation as compared to either one alone (P < 0.05).

Conclusions: This is the first report demonstrating that MGDG enhances the cytotoxicity of radiation to induce apoptosis of cancer cells in vitro and in vivo. Our findings indicate that this therapeutic combination can be an effective strategy for the treatment of pancreatic cancer.

No MeSH data available.


Induction of apoptosis after MGDG, irradiation and their combination in MIAPaCa-2 cells. a Control, b 25 μM MGDG, c 5 Gy radiation, d combination of 25 μM MGDG and 5 Gy radiation
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Fig3: Induction of apoptosis after MGDG, irradiation and their combination in MIAPaCa-2 cells. a Control, b 25 μM MGDG, c 5 Gy radiation, d combination of 25 μM MGDG and 5 Gy radiation

Mentions: The single treatments increased the rate of apoptosis (5.2% for MGDG and 8.8% for radiation), while the combination of both yielded a higher proportion of apoptotic cells (21.5%), suggesting that they had a synergistic effect on apoptosis induction (Fig. 3).Fig. 3


MGDG extracted from spinach enhances the cytotoxicity of radiation in pancreatic cancer cells
Induction of apoptosis after MGDG, irradiation and their combination in MIAPaCa-2 cells. a Control, b 25 μM MGDG, c 5 Gy radiation, d combination of 25 μM MGDG and 5 Gy radiation
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Related In: Results  -  Collection

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Fig3: Induction of apoptosis after MGDG, irradiation and their combination in MIAPaCa-2 cells. a Control, b 25 μM MGDG, c 5 Gy radiation, d combination of 25 μM MGDG and 5 Gy radiation
Mentions: The single treatments increased the rate of apoptosis (5.2% for MGDG and 8.8% for radiation), while the combination of both yielded a higher proportion of apoptotic cells (21.5%), suggesting that they had a synergistic effect on apoptosis induction (Fig. 3).Fig. 3

View Article: PubMed Central - PubMed

ABSTRACT

Background: In our previous study, monogalactosyl diacylglycerol (MGDG) purified from spinach was found to have cytotoxic effects in human cancer cell lines. This study further assessed whether MGDG can enhance the cytotoxic effects of radiation in human pancreatic cancer cells in vitro and in vivo.

Methods: Glycoglycerolipids from spinach including MGDG were extracted from dried spinach. The cytotoxicity of MGDG were evaluated by the MTT assay using four human pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal human dermal fibroblasts (NHDFs). The effects of radiation and MGDG alone or in combination in MIAPaCa-2 cells was analyzed with the colony forming and apoptosis assays, western blotting and cell cycle and DNA damage analyses (γ-H2AX foci staining and comet assay). The inhibitory effects on tumor growth were assessed in a mouse xenograft tumor model.

Results: MGDG showed dose- and time-dependent cytotoxicity, with half-maximal inhibitory concentrations (IC50) in PANC-1, BxPC-3, MIAPaCa-2 and AsPC-1 cells at 72 h of 25.6 ± 2.5, 26.9 ± 1.3, 18.5 ± 1.7, and 22.7 ± 1.9 μM, respectively. The colony forming assay revealed fewer MIAPaCa-2, BxPC-3 and AsPC-1 cell colonies upon treatment with both MGDG and radiation as compared to irradiation alone (P < 0.05). The combination of MGDG and radiation induced a higher proportion of apoptosis in MIAPaCa-2 cells; this effect was associated with increased mitochondrial release of cytochrome c and activation of cleaved poly (ADP-ribose) polymerase and caspase-3. DNA damage was detected and DNA repair mechanisms were more frequently impaired in cells receiving the combination treatment as compared to either one alone. Tumor growth was inhibited to a greater degree in mice treated by intratumoral injection of MGDG combined with irradiation as compared to either one alone (P < 0.05).

Conclusions: This is the first report demonstrating that MGDG enhances the cytotoxicity of radiation to induce apoptosis of cancer cells in vitro and in vivo. Our findings indicate that this therapeutic combination can be an effective strategy for the treatment of pancreatic cancer.

No MeSH data available.