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γ-Tocotrienol induces paraptosis-like cell death in human colon carcinoma SW620 cells.

Zhang JS, Li DM, Ma Y, He N, Gu Q, Wang FS, Jiang SQ, Chen BQ, Liu JR - PLoS ONE (2013)

Bottom Line: We showed that treatment with different concentrations of γ-tocotrienol resulted in a dose dependent inhibition of cell growth.Cell death induced by γ-tocotrienol was mediated by a paraptosis-like cell death in SW620 and HCT-8 cells.These data suggest that a paraptosis-like cell death induced by γ-tocotrienol in SW620 cells is associated with the suppression of the Wnt signaling pathway, which offers a novel tool for treating apoptosis-resistance colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology, Tianjin Center for Disease Control and Prevention, Tianjin, People's Republic of China.

ABSTRACT
Colorectal cancer is one of the most serious illnesses among diagnosed cancer. As a new type of anti-cancer composition from tocotrienol-rich fraction of palm oil, γ-tocotrienol is widely used in anti-cancer research. The objectives of this study were to investigate the effects of γ-tocotrienol on human colon cancer SW620 and HCT-8 cells. We showed that treatment with different concentrations of γ-tocotrienol resulted in a dose dependent inhibition of cell growth. Cell death induced by γ-tocotrienol was mediated by a paraptosis-like cell death in SW620 and HCT-8 cells. Real-time RT-PCR and western blot analyses showed that γ-tocotrienol inhibited the expression level of β-catenin, cyclin D1 and c-jun. These data suggest that a paraptosis-like cell death induced by γ-tocotrienol in SW620 cells is associated with the suppression of the Wnt signaling pathway, which offers a novel tool for treating apoptosis-resistance colon cancer.

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The cellular caspase-3 activity and DNA ladder were examined in SW620 cells or HCT-8 cells.The cellular caspase-3 activity was determined in SW620 cells (I) and HCT-8 cells (II) treated with different doses of γ-tocotrienol as well as DNA ladder in SW620 cells treated with PBS (A), 1.0 and 1.5 µmol/L of PTX or γ-tocotrienol (D) for 24 h. There are no difference between the treated and control groups.
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pone-0057779-g006: The cellular caspase-3 activity and DNA ladder were examined in SW620 cells or HCT-8 cells.The cellular caspase-3 activity was determined in SW620 cells (I) and HCT-8 cells (II) treated with different doses of γ-tocotrienol as well as DNA ladder in SW620 cells treated with PBS (A), 1.0 and 1.5 µmol/L of PTX or γ-tocotrienol (D) for 24 h. There are no difference between the treated and control groups.

Mentions: We further examined the cell growth state distribution and activation of caspase-3 in SW620 cells treated with γ-tocotrienol for 24 h. The cell growth state distribution was determined by flow cytometry. By using the Annexin V-EGFP and PI dye, SW620 cells were divided into three types including viable cells (annexin V-EGFP–, PI–), non-viable necrotic cells in late apoptotic cells (annexin V-EGFP+, PI+) and early apoptotic cells (annexin V-EGFP+, PI–). As shown in Fig. 5 and Fig. 6, the proportion of early apoptotic cells was below 6.0% in all groups, and a peak of cell death was found in SW620 cells treated with 60 µmol/L of γ-tocotrienol. In order to determine caspase-3 activation, SW620 cells were pre-treated with z.VAD.fmk, a pan-specific caspase inhibitor and then treated with different concentrations of γ-tocotrienol for 24 h. The rate of cell viability was measured in the treated and control groups (Fig. 7). The results showed that the percentage of viable cells was declined in all groups, and γ-tocotrienol had the same effect on SW620 with/without z.VAD.fmk. It indicated that γ-tocotrienol-induced cell death is caspase-independent. Caspase-3 activation was also examined in this study. The relative ratios of caspase-3 activation were 74.3±5.2, 72.9±7.3, 72.4±6.3 and 78.6±5.8% in SW620 cells treated with 15, 30, 45 and 60 µmol/L of γ-tocotrienol, respectively (Fig. 6 I). There was no significant change among the treated groups and the control group (P>0.05). As shown in Fig. 6 II, the caspase-3 activity also determined in HCT-8 cells after treated with different doses of γ-tocotrienol (10, 20, 30 and 40 µmol/L). The results showed that γ-tocotrienol-induced cell death in HCT-8 cells was also caspase-independent. In the meantime, DNA ladder assay also used to determine apoptosis in this study. The results showed that PTX at doses of 1.0 and 1.5 µmol/L induced the formation of DNA ladder in SW620 cells. γ-Tocotrienol did not induce the formation of DNA ladder in SW620 cells (Fig. 6 III).


γ-Tocotrienol induces paraptosis-like cell death in human colon carcinoma SW620 cells.

Zhang JS, Li DM, Ma Y, He N, Gu Q, Wang FS, Jiang SQ, Chen BQ, Liu JR - PLoS ONE (2013)

The cellular caspase-3 activity and DNA ladder were examined in SW620 cells or HCT-8 cells.The cellular caspase-3 activity was determined in SW620 cells (I) and HCT-8 cells (II) treated with different doses of γ-tocotrienol as well as DNA ladder in SW620 cells treated with PBS (A), 1.0 and 1.5 µmol/L of PTX or γ-tocotrienol (D) for 24 h. There are no difference between the treated and control groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585143&req=5

pone-0057779-g006: The cellular caspase-3 activity and DNA ladder were examined in SW620 cells or HCT-8 cells.The cellular caspase-3 activity was determined in SW620 cells (I) and HCT-8 cells (II) treated with different doses of γ-tocotrienol as well as DNA ladder in SW620 cells treated with PBS (A), 1.0 and 1.5 µmol/L of PTX or γ-tocotrienol (D) for 24 h. There are no difference between the treated and control groups.
Mentions: We further examined the cell growth state distribution and activation of caspase-3 in SW620 cells treated with γ-tocotrienol for 24 h. The cell growth state distribution was determined by flow cytometry. By using the Annexin V-EGFP and PI dye, SW620 cells were divided into three types including viable cells (annexin V-EGFP–, PI–), non-viable necrotic cells in late apoptotic cells (annexin V-EGFP+, PI+) and early apoptotic cells (annexin V-EGFP+, PI–). As shown in Fig. 5 and Fig. 6, the proportion of early apoptotic cells was below 6.0% in all groups, and a peak of cell death was found in SW620 cells treated with 60 µmol/L of γ-tocotrienol. In order to determine caspase-3 activation, SW620 cells were pre-treated with z.VAD.fmk, a pan-specific caspase inhibitor and then treated with different concentrations of γ-tocotrienol for 24 h. The rate of cell viability was measured in the treated and control groups (Fig. 7). The results showed that the percentage of viable cells was declined in all groups, and γ-tocotrienol had the same effect on SW620 with/without z.VAD.fmk. It indicated that γ-tocotrienol-induced cell death is caspase-independent. Caspase-3 activation was also examined in this study. The relative ratios of caspase-3 activation were 74.3±5.2, 72.9±7.3, 72.4±6.3 and 78.6±5.8% in SW620 cells treated with 15, 30, 45 and 60 µmol/L of γ-tocotrienol, respectively (Fig. 6 I). There was no significant change among the treated groups and the control group (P>0.05). As shown in Fig. 6 II, the caspase-3 activity also determined in HCT-8 cells after treated with different doses of γ-tocotrienol (10, 20, 30 and 40 µmol/L). The results showed that γ-tocotrienol-induced cell death in HCT-8 cells was also caspase-independent. In the meantime, DNA ladder assay also used to determine apoptosis in this study. The results showed that PTX at doses of 1.0 and 1.5 µmol/L induced the formation of DNA ladder in SW620 cells. γ-Tocotrienol did not induce the formation of DNA ladder in SW620 cells (Fig. 6 III).

Bottom Line: We showed that treatment with different concentrations of γ-tocotrienol resulted in a dose dependent inhibition of cell growth.Cell death induced by γ-tocotrienol was mediated by a paraptosis-like cell death in SW620 and HCT-8 cells.These data suggest that a paraptosis-like cell death induced by γ-tocotrienol in SW620 cells is associated with the suppression of the Wnt signaling pathway, which offers a novel tool for treating apoptosis-resistance colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology, Tianjin Center for Disease Control and Prevention, Tianjin, People's Republic of China.

ABSTRACT
Colorectal cancer is one of the most serious illnesses among diagnosed cancer. As a new type of anti-cancer composition from tocotrienol-rich fraction of palm oil, γ-tocotrienol is widely used in anti-cancer research. The objectives of this study were to investigate the effects of γ-tocotrienol on human colon cancer SW620 and HCT-8 cells. We showed that treatment with different concentrations of γ-tocotrienol resulted in a dose dependent inhibition of cell growth. Cell death induced by γ-tocotrienol was mediated by a paraptosis-like cell death in SW620 and HCT-8 cells. Real-time RT-PCR and western blot analyses showed that γ-tocotrienol inhibited the expression level of β-catenin, cyclin D1 and c-jun. These data suggest that a paraptosis-like cell death induced by γ-tocotrienol in SW620 cells is associated with the suppression of the Wnt signaling pathway, which offers a novel tool for treating apoptosis-resistance colon cancer.

Show MeSH
Related in: MedlinePlus