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Asiatic acid impedes NSCLC progression by inhibiting COX-2 and modulating PI3K signaling

Jyoti Singh1,2, Yusuf Hussain1,3, Abha Meena1,3

  • 1Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India.

FEBS Letters
|October 11, 2024
PubMed

Insights

Asiatic acid shows promise for treating non-small cell lung cancer by inhibiting cancer cell growth and spread. This natural compound targets key pathways involved in cancer proliferation and mobility, offering a potential new therapeutic strategy.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Non-small cell lung cancer (NSCLC) has a poor prognosis with limited effective treatments.
  • The cyclooxygenase-2 (COX-2) and lipoxygenase-5 (5-LOX) pathways are implicated in lung cancer development.
  • Targeting these pathways presents a potential therapeutic avenue for NSCLC.

Purpose of the Study:

  • To investigate the therapeutic potential of asiatic acid (AA), a triterpenoid saponin, against non-small cell lung cancer.
  • To elucidate the molecular mechanisms by which AA affects lung cancer cell proliferation, mobility, and survival.
  • To evaluate the role of AA in targeting COX-2 and associated signaling pathways.

Main Methods:

  • In vitro studies using lung cancer cell lines to assess the effects of asiatic acid.
  • Analysis of signaling pathways including COX-2, phosphotidyl inositol-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), and mitogen-activated protein kinase (MAPK).
  • Assessment of cell proliferation, apoptosis, autophagy, cell mobility, and invasion.

Main Results:

  • Asiatic acid significantly inhibited lung cancer cell growth by over 50%.
  • AA suppressed COX-2 expression, leading to downregulation of the PI3K/Akt/mTOR pathway and inducing apoptosis via autophagy.
  • AA reduced cell mobility and invasion by downregulating MAPK/ERK, HIF-1, and VEGF expression.
  • AA demonstrated negative osmotic fragility on human erythrocytes, indicating a favorable safety profile.

Conclusions:

  • Asiatic acid exhibits significant anti-cancer effects against non-small cell lung cancer cells.
  • AA acts by inhibiting COX-2, modulating key cell signaling pathways, and inducing cancer cell death.
  • Asiatic acid represents a potential therapeutic candidate for NSCLC, warranting further investigation and analogue development.
Keywords:
apoptosisasiatic acidautophagylung‐cancermobilitytriterpenoid

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