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Aurantoside C Targets and Induces Apoptosis in Triple Negative Breast Cancer Cells

Sumi Shrestha1,2, Anabel Sorolla3, Jane Fromont4

  • 1School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia. sumi.shrestha@research.uwa.edu.au.

Marine Drugs
|October 3, 2018
PubMed

Insights

Aurantoside C (C828), derived from a marine sponge, shows potent anti-cancer activity against triple-negative breast cancer (TNBC) cells. This compound offers a promising new avenue for targeted TNBC therapy, outperforming existing treatments.

Area of Science:

  • Marine Natural Products Chemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Triple-negative breast cancer (TNBC) lacks effective targeted therapies.
  • Marine sponges are a source of novel bioactive compounds.
  • Developing new TNBC treatments is a critical unmet need.

Purpose of the Study:

  • To investigate the cytotoxic effects of aurantoside C (C828) on TNBC cells.
  • To elucidate the molecular mechanisms underlying C828's activity.
  • To compare C828's potency with conventional chemotherapeutic agents.

Main Methods:

  • Isolation of aurantoside C (C828) from the marine sponge *Manihinea lynbeazleyae*.
  • In vitro cytotoxicity assays on TNBC and non-TNBC cell lines.
  • Cell cycle analysis and Western blotting to assess molecular targets.
  • Comparison of IC50 values with doxorubicin and cisplatin.

Main Results:

  • C828 demonstrated significantly higher cytotoxicity in TNBC cells compared to non-TNBC cells.
  • C828 induced S-phase arrest and modulated key cell cycle regulatory proteins (cyclin D1, E1, CDK4, CDK6, p21).
  • C828 inhibited Akt/mTOR and NF-kB pathways while activating p38 MAPK and SAPK/JNK pathways, promoting apoptosis.
  • C828 was 20-35 times more potent than doxorubicin and cisplatin against TNBC cells.

Conclusions:

  • Aurantoside C (C828) exhibits potent and selective anti-TNBC activity.
  • C828's mechanism involves cell cycle arrest, apoptosis induction, and modulation of key signaling pathways.
  • C828 represents a promising lead compound for the development of novel targeted therapies for triple-negative breast cancer.
Keywords:
apoptosisaurantoside Ccell cycle analysismarine spongetriple negative breast cancer

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