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Hesperidin Induces Apoptosis by Inhibiting Sp1 and Its Regulatory Protein in MSTO-211H Cells.

Lee KA, Lee SH, Lee YJ, Baeg SM, Shim JH - Biomol Ther (Seoul) (2012)

Bottom Line: The IC50 value of hesperidin was determined to be 152.3 μM in MSTO-211H cells for 48 h.Our results suggested that hesperidin (0-160 μM) decreased cell viability, and induced apoptotic cell death.Hesperidin increased Sub-G1 population in MSTO-211H cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, College of Medicine, Soonchunhyang University.

ABSTRACT
Hesperidin, a flavanone present in citrus fruits, has been studied as potential therapeutic agents that have anti-tumor activity and apoptotic effects in several cancers, but there is no report about the apoptotic effect of hesperidin in human malignant pleural mesothelioma through the specificity protein 1 (Sp1) protein. We investigated whether hesperidin inhibited cell growth and regulated Sp1 target proteins by suppressing the levels of Sp1 protein in MSTO-211H cells. The IC50 value of hesperidin was determined to be 152.3 μM in MSTO-211H cells for 48 h. Our results suggested that hesperidin (0-160 μM) decreased cell viability, and induced apoptotic cell death. Hesperidin increased Sub-G1 population in MSTO-211H cells. Hesperidin significantly suppressed mRNA/protein level of Sp1 and modulated the expression level of the Sp1 regulatory protein such as p27, p21, cyclin D1, Mcl-1, and survivin in mesothelioma cells. Also, hesperidin induced apoptotic signaling including: cleavages of Bid, caspase-3, and PARP, upregulation of Bax, and down-regulation of Bcl-xl in mesothelioma cells. These results show that hesperidin suppressed mesothelioma cell growth through inhibition of Sp1. In this study, we demonstrated that Sp1 acts as a novel molecular target of hesperidin in human malignant pleural mesothelioma.

No MeSH data available.


Related in: MedlinePlus

The effect of hesperidin on cell viability in MSTO-211H cells. (A) Chemical structure of hesperidin. (B) Cell viability effectsof hesperidin on MSTO-211H cells. MSTO-211H cells (3×103 cells/200 μl) were treated with hesperidin (40-160 μM) in 5% FBS-RPMI1640 for 24 h and 48 h. Cell viabilities were measured with MTS assay, as described under “Material and Methods”. Results are indicated as cell viability relative to untreated with hesperidin, as determined from three independent experiments. Data representedas mean ± SD. The asterisk indicated a significant difference compared with the negative control (*p<0.05). (C) Cell morphological changes in MSTO-211H cells treated or untreated with hesperidin for 48 h.
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Figure 001: The effect of hesperidin on cell viability in MSTO-211H cells. (A) Chemical structure of hesperidin. (B) Cell viability effectsof hesperidin on MSTO-211H cells. MSTO-211H cells (3×103 cells/200 μl) were treated with hesperidin (40-160 μM) in 5% FBS-RPMI1640 for 24 h and 48 h. Cell viabilities were measured with MTS assay, as described under “Material and Methods”. Results are indicated as cell viability relative to untreated with hesperidin, as determined from three independent experiments. Data representedas mean ± SD. The asterisk indicated a significant difference compared with the negative control (*p<0.05). (C) Cell morphological changes in MSTO-211H cells treated or untreated with hesperidin for 48 h.

Mentions: Hesperidin (30,5,9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavanone present in citrus fruits like oranges and lemons (Justesen et al., 1998; Nielsen et al., 2002) (Fig. 1A). Hesperidin was first discovered in 1827, but had been studied as a combination product complex until 1986 (Garg et al., 2001). In nature, hesperidin exist as glycoside form, a beta-7-rutinoside of hesperitin, but dietary hesperidin is hydrolyzed to hesperitin (Preston et al., 1953; Ameer et al., 1996). Hesperidin


Hesperidin Induces Apoptosis by Inhibiting Sp1 and Its Regulatory Protein in MSTO-211H Cells.

Lee KA, Lee SH, Lee YJ, Baeg SM, Shim JH - Biomol Ther (Seoul) (2012)

The effect of hesperidin on cell viability in MSTO-211H cells. (A) Chemical structure of hesperidin. (B) Cell viability effectsof hesperidin on MSTO-211H cells. MSTO-211H cells (3×103 cells/200 μl) were treated with hesperidin (40-160 μM) in 5% FBS-RPMI1640 for 24 h and 48 h. Cell viabilities were measured with MTS assay, as described under “Material and Methods”. Results are indicated as cell viability relative to untreated with hesperidin, as determined from three independent experiments. Data representedas mean ± SD. The asterisk indicated a significant difference compared with the negative control (*p<0.05). (C) Cell morphological changes in MSTO-211H cells treated or untreated with hesperidin for 48 h.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3794523&req=5

Figure 001: The effect of hesperidin on cell viability in MSTO-211H cells. (A) Chemical structure of hesperidin. (B) Cell viability effectsof hesperidin on MSTO-211H cells. MSTO-211H cells (3×103 cells/200 μl) were treated with hesperidin (40-160 μM) in 5% FBS-RPMI1640 for 24 h and 48 h. Cell viabilities were measured with MTS assay, as described under “Material and Methods”. Results are indicated as cell viability relative to untreated with hesperidin, as determined from three independent experiments. Data representedas mean ± SD. The asterisk indicated a significant difference compared with the negative control (*p<0.05). (C) Cell morphological changes in MSTO-211H cells treated or untreated with hesperidin for 48 h.
Mentions: Hesperidin (30,5,9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavanone present in citrus fruits like oranges and lemons (Justesen et al., 1998; Nielsen et al., 2002) (Fig. 1A). Hesperidin was first discovered in 1827, but had been studied as a combination product complex until 1986 (Garg et al., 2001). In nature, hesperidin exist as glycoside form, a beta-7-rutinoside of hesperitin, but dietary hesperidin is hydrolyzed to hesperitin (Preston et al., 1953; Ameer et al., 1996). Hesperidin

Bottom Line: The IC50 value of hesperidin was determined to be 152.3 μM in MSTO-211H cells for 48 h.Our results suggested that hesperidin (0-160 μM) decreased cell viability, and induced apoptotic cell death.Hesperidin increased Sub-G1 population in MSTO-211H cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, College of Medicine, Soonchunhyang University.

ABSTRACT
Hesperidin, a flavanone present in citrus fruits, has been studied as potential therapeutic agents that have anti-tumor activity and apoptotic effects in several cancers, but there is no report about the apoptotic effect of hesperidin in human malignant pleural mesothelioma through the specificity protein 1 (Sp1) protein. We investigated whether hesperidin inhibited cell growth and regulated Sp1 target proteins by suppressing the levels of Sp1 protein in MSTO-211H cells. The IC50 value of hesperidin was determined to be 152.3 μM in MSTO-211H cells for 48 h. Our results suggested that hesperidin (0-160 μM) decreased cell viability, and induced apoptotic cell death. Hesperidin increased Sub-G1 population in MSTO-211H cells. Hesperidin significantly suppressed mRNA/protein level of Sp1 and modulated the expression level of the Sp1 regulatory protein such as p27, p21, cyclin D1, Mcl-1, and survivin in mesothelioma cells. Also, hesperidin induced apoptotic signaling including: cleavages of Bid, caspase-3, and PARP, upregulation of Bax, and down-regulation of Bcl-xl in mesothelioma cells. These results show that hesperidin suppressed mesothelioma cell growth through inhibition of Sp1. In this study, we demonstrated that Sp1 acts as a novel molecular target of hesperidin in human malignant pleural mesothelioma.

No MeSH data available.


Related in: MedlinePlus