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Anticancer effect of tectochrysin in colon cancer cell via suppression of NF-kappaB activity and enhancement of death receptor expression.

Park MH, Hong JE, Park ES, Yoon HS, Seo DW, Hyun BK, Han SB, Ham YW, Hwang BY, Hong JT - Mol. Cancer (2015)

Bottom Line: Flavonoids are a diverse family of natural phenolic compounds commonly found in fruits and vegetables.The expression of DR3, DR4 and Fas were significantly increased, and pro-apoptotic proteins were also increased.A docking model indicated that tectochrysin binds directly to the p50 unit.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea. pmh5205@hanmail.net.

ABSTRACT

Background: Flavonoids are a diverse family of natural phenolic compounds commonly found in fruits and vegetables. Epidemiologic studies showed that flavonoids also reduce the risk of colon cancer. Tectochrysin is one of the major flavonoids of Alpinia oxyphylla Miquel. However, the anti-cancer effects and the molecular mechanisms of tectochrysin in colon cancer cells have not yet been reported. We investigated whether tectochrysin could inhibit colon cancer cell growth at 1, 5, 10 μg/ml. In in vivo study, we injected a tectochrysin treatment dose of 5 mg/kg to each mouse.

Results: Tectochrysin suppressed the growth of SW480 and HCT116 human colon cancer cells. The expression of DR3, DR4 and Fas were significantly increased, and pro-apoptotic proteins were also increased. Tectochrysin treatment also inhibited activity of NF-κB. A docking model indicated that tectochrysin binds directly to the p50 unit. In in vivo, tumor weights and volumes in mice were reduced when treated with tectochrysin. Tectochrysin leads to apoptotic cell death in colon cancer cells through activation of death receptors expression via the inhibition of NF-κB.

Conclusions: Tectochrysin can be a useful agent for the treatment of colon cancer cell growth as well as an adjuvant agent for chemo-resistant cancer cells growth.

No MeSH data available.


Related in: MedlinePlus

Effect of tectochrysin on the expression of apoptosis regulatory proteins and death receptors, and activation NF-κB in colon cancer cells. The colon cancer cells were treated with different concentrations of tectochrysin (1, 5 and 10 μg/mL) for 24 h or for 1 h (for NF-κB assay). Equal amounts of total proteins (20 μg/lane) were subjected to 10 % or 15 % SDS-PAGE. a Expression of cIAP1, XIAP, Bax, Bcl-2, Bid, Cyto-C, cleaved caspase-3, -8, -9, cleaved PARP and β-actin was detected by Western Blotting using specific antibodies. b Expression of DR3, DR4, Fas, and β−actin was detected by Western blotting using specific antibodies. c Activation of NF-κB was investigated using EMSA as described in Methods. After, the cells were treated with different concentrations (1, 5 and 10 μg/mL) of tectochrysin at 37 °C for 1 h, nuclear or cytosolic proteins were extracted and the expression of p50, p65, IκB-α, and p-IκB-α proteins was detected by Western blotting using specific antibodies. β-actin and histone-H1 proteins were used as internal controls. Each band is representative for three experiments. Values below the band are average of band density. (CE: cytosolic extraction, NE: nuclear extraction)
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Fig2: Effect of tectochrysin on the expression of apoptosis regulatory proteins and death receptors, and activation NF-κB in colon cancer cells. The colon cancer cells were treated with different concentrations of tectochrysin (1, 5 and 10 μg/mL) for 24 h or for 1 h (for NF-κB assay). Equal amounts of total proteins (20 μg/lane) were subjected to 10 % or 15 % SDS-PAGE. a Expression of cIAP1, XIAP, Bax, Bcl-2, Bid, Cyto-C, cleaved caspase-3, -8, -9, cleaved PARP and β-actin was detected by Western Blotting using specific antibodies. b Expression of DR3, DR4, Fas, and β−actin was detected by Western blotting using specific antibodies. c Activation of NF-κB was investigated using EMSA as described in Methods. After, the cells were treated with different concentrations (1, 5 and 10 μg/mL) of tectochrysin at 37 °C for 1 h, nuclear or cytosolic proteins were extracted and the expression of p50, p65, IκB-α, and p-IκB-α proteins was detected by Western blotting using specific antibodies. β-actin and histone-H1 proteins were used as internal controls. Each band is representative for three experiments. Values below the band are average of band density. (CE: cytosolic extraction, NE: nuclear extraction)

Mentions: The relationship between the induction of apoptotic cell death by tectochrysin and the expression of apoptosis related protein was investigated. In agreement with the induction of apoptotic cell death, expression of apoptotic proteins such as cleaved caspase-3, -8, -9, cleaved PARP, Bid, cytochrome-C and Bax was increased, but expression of Bcl-2, cIAP1 and XIAP was decreased in both SW480 and HCT116 colon cancer cells in a concentration dependent manner (Fig. 2a). The extrinsic pathway of apoptotic cell death requires induction of DRs expression. Moreover, expression of DRs is critical for activation of caspase-3. Therefore, we investigated the effect of tectochrysin on the expression of DRs. The expression of DR3, DR4 and Fas was highly induced by tectochrysin in a concentration-dependent manner in both SW480 and HCT116 colon cancer cells (Fig. 2b), but expressions of other DRs were not changed (data not shown). Our data indicated that tectochrysin induced intrinsic apoptosis by elevation of the BAX/BCL2 ratio, cytochromeC and cleaved caspase-3 and-9, and extrinsic pathway by increase of death receptors and cleavage caspase-8. Thus, Tectochrysin may act both intrinsic apoptosis and extrinsic apoptosis pathway.Fig. 2


Anticancer effect of tectochrysin in colon cancer cell via suppression of NF-kappaB activity and enhancement of death receptor expression.

Park MH, Hong JE, Park ES, Yoon HS, Seo DW, Hyun BK, Han SB, Ham YW, Hwang BY, Hong JT - Mol. Cancer (2015)

Effect of tectochrysin on the expression of apoptosis regulatory proteins and death receptors, and activation NF-κB in colon cancer cells. The colon cancer cells were treated with different concentrations of tectochrysin (1, 5 and 10 μg/mL) for 24 h or for 1 h (for NF-κB assay). Equal amounts of total proteins (20 μg/lane) were subjected to 10 % or 15 % SDS-PAGE. a Expression of cIAP1, XIAP, Bax, Bcl-2, Bid, Cyto-C, cleaved caspase-3, -8, -9, cleaved PARP and β-actin was detected by Western Blotting using specific antibodies. b Expression of DR3, DR4, Fas, and β−actin was detected by Western blotting using specific antibodies. c Activation of NF-κB was investigated using EMSA as described in Methods. After, the cells were treated with different concentrations (1, 5 and 10 μg/mL) of tectochrysin at 37 °C for 1 h, nuclear or cytosolic proteins were extracted and the expression of p50, p65, IκB-α, and p-IκB-α proteins was detected by Western blotting using specific antibodies. β-actin and histone-H1 proteins were used as internal controls. Each band is representative for three experiments. Values below the band are average of band density. (CE: cytosolic extraction, NE: nuclear extraction)
© Copyright Policy - open-access
Related In: Results  -  Collection

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Fig2: Effect of tectochrysin on the expression of apoptosis regulatory proteins and death receptors, and activation NF-κB in colon cancer cells. The colon cancer cells were treated with different concentrations of tectochrysin (1, 5 and 10 μg/mL) for 24 h or for 1 h (for NF-κB assay). Equal amounts of total proteins (20 μg/lane) were subjected to 10 % or 15 % SDS-PAGE. a Expression of cIAP1, XIAP, Bax, Bcl-2, Bid, Cyto-C, cleaved caspase-3, -8, -9, cleaved PARP and β-actin was detected by Western Blotting using specific antibodies. b Expression of DR3, DR4, Fas, and β−actin was detected by Western blotting using specific antibodies. c Activation of NF-κB was investigated using EMSA as described in Methods. After, the cells were treated with different concentrations (1, 5 and 10 μg/mL) of tectochrysin at 37 °C for 1 h, nuclear or cytosolic proteins were extracted and the expression of p50, p65, IκB-α, and p-IκB-α proteins was detected by Western blotting using specific antibodies. β-actin and histone-H1 proteins were used as internal controls. Each band is representative for three experiments. Values below the band are average of band density. (CE: cytosolic extraction, NE: nuclear extraction)
Mentions: The relationship between the induction of apoptotic cell death by tectochrysin and the expression of apoptosis related protein was investigated. In agreement with the induction of apoptotic cell death, expression of apoptotic proteins such as cleaved caspase-3, -8, -9, cleaved PARP, Bid, cytochrome-C and Bax was increased, but expression of Bcl-2, cIAP1 and XIAP was decreased in both SW480 and HCT116 colon cancer cells in a concentration dependent manner (Fig. 2a). The extrinsic pathway of apoptotic cell death requires induction of DRs expression. Moreover, expression of DRs is critical for activation of caspase-3. Therefore, we investigated the effect of tectochrysin on the expression of DRs. The expression of DR3, DR4 and Fas was highly induced by tectochrysin in a concentration-dependent manner in both SW480 and HCT116 colon cancer cells (Fig. 2b), but expressions of other DRs were not changed (data not shown). Our data indicated that tectochrysin induced intrinsic apoptosis by elevation of the BAX/BCL2 ratio, cytochromeC and cleaved caspase-3 and-9, and extrinsic pathway by increase of death receptors and cleavage caspase-8. Thus, Tectochrysin may act both intrinsic apoptosis and extrinsic apoptosis pathway.Fig. 2

Bottom Line: Flavonoids are a diverse family of natural phenolic compounds commonly found in fruits and vegetables.The expression of DR3, DR4 and Fas were significantly increased, and pro-apoptotic proteins were also increased.A docking model indicated that tectochrysin binds directly to the p50 unit.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea. pmh5205@hanmail.net.

ABSTRACT

Background: Flavonoids are a diverse family of natural phenolic compounds commonly found in fruits and vegetables. Epidemiologic studies showed that flavonoids also reduce the risk of colon cancer. Tectochrysin is one of the major flavonoids of Alpinia oxyphylla Miquel. However, the anti-cancer effects and the molecular mechanisms of tectochrysin in colon cancer cells have not yet been reported. We investigated whether tectochrysin could inhibit colon cancer cell growth at 1, 5, 10 μg/ml. In in vivo study, we injected a tectochrysin treatment dose of 5 mg/kg to each mouse.

Results: Tectochrysin suppressed the growth of SW480 and HCT116 human colon cancer cells. The expression of DR3, DR4 and Fas were significantly increased, and pro-apoptotic proteins were also increased. Tectochrysin treatment also inhibited activity of NF-κB. A docking model indicated that tectochrysin binds directly to the p50 unit. In in vivo, tumor weights and volumes in mice were reduced when treated with tectochrysin. Tectochrysin leads to apoptotic cell death in colon cancer cells through activation of death receptors expression via the inhibition of NF-κB.

Conclusions: Tectochrysin can be a useful agent for the treatment of colon cancer cell growth as well as an adjuvant agent for chemo-resistant cancer cells growth.

No MeSH data available.


Related in: MedlinePlus