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

Our plain-English summary of Hesperidin Induces Apoptosis by Inhibiting Sp1 and Its Regulatory Protein in MSTO-211H Cells, by K.A. Lee, S.H. Lee, Y.J. Lee, et al (Biomolecules & Therapeutics, 2012).

The study

• Authors: K.A. Lee, S.H. Lee, Y.J. Lee, S.M. Baeg, J.H. Shim
• Journal: Biomolecules & Therapeutics
• Published: 2012;20(3):273-9
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory study mainly used one human malignant pleural mesothelioma cell line, MSTO-211H. The authors also briefly reported, without showing data, a result in a second malignant mesothelioma cell line, HT28. No people, animals or asbestos exposure were studied. The authors treated the cells with hesperidin, a citrus-fruit compound, for 24 and 48 hours, at concentrations the article prints as 0, 40, 80 and 160 mM. The concentration that halved MSTO-211H viability at 48 hours was about 152.3 mM; the authors gave about 154 mM for HT28. MSTO-211H viability was 82.0, 77.7 and 53.9 percent of untreated cells at 40, 80 and 160 mM. Treated cells showed signs of programmed cell death (apoptosis). The authors reported lower levels of a protein called Sp1 and of several proteins it regulates. Blocking Sp1 directly also reduced cell viability. The authors concluded that Sp1 can be used as an effective therapeutic target and that hesperidin may be a potential cancer drug or supplement for malignant pleural mesothelioma. They noted that its mechanisms still need confirming and that a study in living organisms is needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory (in vitro) cell-culture experiment
• Who was studied: Mainly the human malignant pleural mesothelioma cell line MSTO-211H, purchased from a cell collection and studied at Soonchunhyang University, Republic of Korea. A second malignant mesothelioma cell line, HT28, was mentioned with data not shown. No human subjects or animals were involved.
• Exposure: Hesperidin (a citrus flavanone) at concentrations the article prints as 0, 40, 80 and 160 mM, for 24 and 48 hours. The study also used small interfering RNA to block Sp1. No asbestos or other fiber exposure was studied.
• Main results:
  • In MSTO-211H cells at 48 hours, the concentration of hesperidin that halved viability (IC50) was about 152.3 mM, as printed in the article.
  • MSTO-211H cell viability was 82.0 plus or minus 1.6%, 77.7 plus or minus 1.4%, and 53.9 plus or minus 1.5% of untreated control cells at 40, 80 and 160 mM hesperidin, respectively. The sentence reporting these values does not state the treatment time.
  • In another malignant mesothelioma cell line, HT28, the authors reported an IC50 of about 154 mM. They did not show these data.
  • Hesperidin-treated MSTO-211H cells showed more nuclear condensation and fragmentation, which are signs of apoptosis, than control cells.
  • The Sub-G1 cell population, a measure of dying cells, was reported as 20-35% in MSTO-211H cells treated with 40 to 160 mM hesperidin.
  • Blocking Sp1 with small interfering RNA reduced MSTO-211H cell viability.
  • Sp1 protein and Sp1 mRNA levels in MSTO-211H cells were lower after 40, 80 and 160 mM hesperidin.
  • Hesperidin lowered the Sp1-regulated proteins p27, p21, cyclin D1, Mcl-1 and survivin in MSTO-211H cells.
  • After 48 hours of hesperidin, MSTO-211H cells showed changes in apoptosis-related proteins: activation of PARP and Bid, cleavage of caspase-3, induction of Bax, and down-regulation of Bcl-xl.
• The authors' conclusion: The authors concluded that Sp1 can be used as an effective therapeutic target in cancer research, and that hesperidin may be a potential cancer drug or supplement for malignant pleural mesothelioma.
• Limitations the authors state:
  • How hesperidin works at the molecular level still needs to be confirmed.
  • A study in living organisms (in vivo) is needed before any clinical application in malignant pleural mesothelioma.
  • Hesperidin's toxicity, water-solubility, absorption, optimal dose, interactions and metabolism still need study.

Topics

Medical terms in this study, explained in our Lexicon: Apoptosis, Pleural Mesothelioma, Mesothelioma.

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