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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 cell growth, DR4 and cleaved caspase-3 expression, and NF-κB activity in TRAIL-resistant cancer cell. a HT-29, A549, and MCF-7 cells were pretreated with tectochrysin (3 μg/mL) for 24 h, the media were removed, and the cells were exposed to TRAIL (50 ng/mL in HT-29, A549, and MCF-7 cells) for 24 h. The effect of tectochrysin on resistant cancer cell growth was determined by MTT assay. The data are expressed as the mean ± SD of three experiments. *P < 0.05 compared with the control. #P < 0.05 compared with the treated TARIL treated cells. b Expression of DR4, p-IκB, IκB, p50, β-actin and histone-H1 was detected by Western blotting using specific antibodies. β-actin and histone-H1 proteins were used as internal controls. c The activation of NF-κB was investigated using EMSA as described in Methods. Each band is representative for three experiments. Values below the band are average of band density
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Fig5: Effect of tectochrysin on cell growth, DR4 and cleaved caspase-3 expression, and NF-κB activity in TRAIL-resistant cancer cell. a HT-29, A549, and MCF-7 cells were pretreated with tectochrysin (3 μg/mL) for 24 h, the media were removed, and the cells were exposed to TRAIL (50 ng/mL in HT-29, A549, and MCF-7 cells) for 24 h. The effect of tectochrysin on resistant cancer cell growth was determined by MTT assay. The data are expressed as the mean ± SD of three experiments. *P < 0.05 compared with the control. #P < 0.05 compared with the treated TARIL treated cells. b Expression of DR4, p-IκB, IκB, p50, β-actin and histone-H1 was detected by Western blotting using specific antibodies. β-actin and histone-H1 proteins were used as internal controls. c The activation of NF-κB was investigated using EMSA as described in Methods. Each band is representative for three experiments. Values below the band are average of band density

Mentions: The human colon cancer cell lines SW480 and HCT116 are known to be TRAIL-sensitive, while HT-29 (human colon cancer cell), A549 (human lung cancer cell) and MCF-7 (human breast cancer cell) are TRAIL-resistant [26]. The aim of this study was to investigate whether tectochrysin can enhance the sensitivity of TRAIL resistant cancer cells to TRAIL and possible mechanisms. We treated these cancer cells with half a dose of IC50 tectochrysin (3 μg/mL) and TRAIL (50 ng/mL), and we found that tectochrysin and TRAIL treatments alone induced 18.1 % and 9.6 % cell growth inhibition in HT-29 cells, 21.7 % and 7.1 % in A549 cells and 17.1 % and 20.8 % in MCF-7 cells. However, a combination treatment with tectochrysin and TRAIL enhanced TRAIL induced cell growth inhibition up to 49.6 % in HT-29 TRAIL-resistant colon cancer cells, 40.7 % in A549 TRAIL-resistant lung cancer cells and 46.8 % in MCF-7 TRAIL-resistant breast cancer cells (Fig. 5a). The combination index values of A549 and HT-29 cells were 0.021, and MCF-7 cells was 0.034. These data indicate that tectochrysin leads to a synergistic growth inhibitory effect in TRAIL-resistant cancer cells with TRAIL. In addition, we compared the effect of tectochrysin and/or TRAIL of the activation of caspase-3 and the expression of DR4 in the TRAIL-resistant cancer cells. Although tectochrysin and TRAIL alone had little effect on activation of caspase-3 cleavage and DR4 expression, the combination treatment significantly increased expression of cleaved caspase-3 and DR4 (Fig. 5b). Tectochrysin also further reduced DNA binding activity of NF-κB as well as translocation of p50 in the nucleus and cytosolic p-IκB expression in TRAIL-resistant cancer cells (Fig. 5c).Fig. 5


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 cell growth, DR4 and cleaved caspase-3 expression, and NF-κB activity in TRAIL-resistant cancer cell. a HT-29, A549, and MCF-7 cells were pretreated with tectochrysin (3 μg/mL) for 24 h, the media were removed, and the cells were exposed to TRAIL (50 ng/mL in HT-29, A549, and MCF-7 cells) for 24 h. The effect of tectochrysin on resistant cancer cell growth was determined by MTT assay. The data are expressed as the mean ± SD of three experiments. *P < 0.05 compared with the control. #P < 0.05 compared with the treated TARIL treated cells. b Expression of DR4, p-IκB, IκB, p50, β-actin and histone-H1 was detected by Western blotting using specific antibodies. β-actin and histone-H1 proteins were used as internal controls. c The activation of NF-κB was investigated using EMSA as described in Methods. Each band is representative for three experiments. Values below the band are average of band density
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4487202&req=5

Fig5: Effect of tectochrysin on cell growth, DR4 and cleaved caspase-3 expression, and NF-κB activity in TRAIL-resistant cancer cell. a HT-29, A549, and MCF-7 cells were pretreated with tectochrysin (3 μg/mL) for 24 h, the media were removed, and the cells were exposed to TRAIL (50 ng/mL in HT-29, A549, and MCF-7 cells) for 24 h. The effect of tectochrysin on resistant cancer cell growth was determined by MTT assay. The data are expressed as the mean ± SD of three experiments. *P < 0.05 compared with the control. #P < 0.05 compared with the treated TARIL treated cells. b Expression of DR4, p-IκB, IκB, p50, β-actin and histone-H1 was detected by Western blotting using specific antibodies. β-actin and histone-H1 proteins were used as internal controls. c The activation of NF-κB was investigated using EMSA as described in Methods. Each band is representative for three experiments. Values below the band are average of band density
Mentions: The human colon cancer cell lines SW480 and HCT116 are known to be TRAIL-sensitive, while HT-29 (human colon cancer cell), A549 (human lung cancer cell) and MCF-7 (human breast cancer cell) are TRAIL-resistant [26]. The aim of this study was to investigate whether tectochrysin can enhance the sensitivity of TRAIL resistant cancer cells to TRAIL and possible mechanisms. We treated these cancer cells with half a dose of IC50 tectochrysin (3 μg/mL) and TRAIL (50 ng/mL), and we found that tectochrysin and TRAIL treatments alone induced 18.1 % and 9.6 % cell growth inhibition in HT-29 cells, 21.7 % and 7.1 % in A549 cells and 17.1 % and 20.8 % in MCF-7 cells. However, a combination treatment with tectochrysin and TRAIL enhanced TRAIL induced cell growth inhibition up to 49.6 % in HT-29 TRAIL-resistant colon cancer cells, 40.7 % in A549 TRAIL-resistant lung cancer cells and 46.8 % in MCF-7 TRAIL-resistant breast cancer cells (Fig. 5a). The combination index values of A549 and HT-29 cells were 0.021, and MCF-7 cells was 0.034. These data indicate that tectochrysin leads to a synergistic growth inhibitory effect in TRAIL-resistant cancer cells with TRAIL. In addition, we compared the effect of tectochrysin and/or TRAIL of the activation of caspase-3 and the expression of DR4 in the TRAIL-resistant cancer cells. Although tectochrysin and TRAIL alone had little effect on activation of caspase-3 cleavage and DR4 expression, the combination treatment significantly increased expression of cleaved caspase-3 and DR4 (Fig. 5b). Tectochrysin also further reduced DNA binding activity of NF-κB as well as translocation of p50 in the nucleus and cytosolic p-IκB expression in TRAIL-resistant cancer cells (Fig. 5c).Fig. 5

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