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Marine Peroxy Sesquiterpenoids Induce Apoptosis by Modulation of Nrf2-ARE Signaling in HCT116 Colon Cancer Cells

Junsei Taira1, Haruna Miyazato2, Katsuhiro Ueda3

  • 1Department Bioresource Technology, Okinawa National College of Technology, 905 Henoko, Nago-city Okinawa Prefecture 905-2192, Japan. taira@okinawa-ct.ac.jp.

Marine Drugs
|September 26, 2018
PubMed

Insights

Marine peroxy sesquiterpenoids from soft coral exhibit antitumor effects by inducing apoptosis in colon cancer cells. These compounds inhibit key survival proteins and modulate the Nrf2-ARE signaling pathway.

Area of Science:

  • Marine natural products chemistry
  • Cancer biology
  • Molecular pharmacology

Background:

  • Soft corals are a rich source of bioactive marine compounds.
  • Peroxy sesquiterpenoids are a class of natural products with diverse biological activities.
  • Colon cancer remains a significant global health challenge requiring novel therapeutic strategies.

Purpose of the Study:

  • To investigate the antitumor activity of marine peroxy sesquiterpenoids isolated from Okinawan soft coral *Sinularia* sp.
  • To elucidate the molecular mechanisms underlying the observed antitumor effects, including apoptosis induction and signaling pathway modulation.

Main Methods:

  • Isolation and characterization of peroxy sesquiterpenoids from *Sinularia* sp.
  • In vitro antitumor activity assessment using human colon cancer cell line (HCT 116).
  • Analysis of apoptosis-related proteins (Bcl-xL, pAkt) and Nrf2-ARE signaling pathway components (HO-1, Nrf2, pNrf2) using Western blotting or similar techniques.

Main Results:

  • Peroxy sesquiterpenoids (compounds 1 and 2) demonstrated significant antitumor activity against HCT 116 cells.
  • The compounds induced apoptosis, evidenced by hydrogen peroxide (H₂O₂) production.
  • Inhibition of anti-apoptotic proteins (Bcl-xL, pAkt) and suppression of Nrf2-ARE signaling pathway proteins (HO-1, Nrf2, pNrf2) were observed.
  • Co-treatment with trolox (antioxidant) partially reversed the suppression of these proteins, suggesting a role for H₂O₂-mediated free radical reactions.

Conclusions:

  • Marine peroxy sesquiterpenoids possess potent antitumor activity against colon cancer cells.
  • Apoptosis induction by these compounds is mediated through H₂O₂ production and modulation of the Nrf2-ARE signaling pathway.
  • These findings highlight the therapeutic potential of soft coral-derived peroxy sesquiterpenoids as anticancer agents.
Keywords:
HCT116 colon cancer cellsNrf2-ARE signalingSinularia sp.apoptosisfree radicalperoxy sesquiterpenoidsoft coral

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