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Cytotoxicity of obacunone and obacunone glucoside in human prostate cancer cells involves Akt-mediated programmed

Kotamballi N Chidambara Murthy1, Guddadarangavvanahally K Jayaprakasha1, Bhimanagouda S Patil1

  • 1Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77845-2119, United States.

Toxicology
|January 17, 2015
PubMed

Insights

Citrus compounds obacunone and obacunone glucoside (OG) show significant cytotoxicity against prostate cancer cells. These natural triterpenoids induce programmed cell death and inhibit cancer cell proliferation through multiple pathways.

Area of Science:

  • Natural Products Chemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Obacunone and obacunone glucoside (OG) are triterpenoids found in citrus plants.
  • Prostate cancer remains a significant health concern, particularly androgen-dependent forms.

Purpose of the Study:

  • To investigate the cytotoxic mechanisms of obacunone and OG on human androgen-dependent prostate cancer LNCaP cells.
  • To elucidate the pathways involved in the anti-cancer effects of these citrus-derived limonoids.

Main Methods:

  • Cell viability assays to determine proliferation inhibition.
  • Analysis of DNA fragmentation, caspase-3 activity, and cytochrome-c release to assess apoptosis.
  • Western blotting to evaluate protein expression changes related to apoptosis, cell signaling, and cell cycle.

Main Results:

  • Obacunone and OG demonstrated dose- and time-dependent inhibition of LNCaP cell proliferation (>60% viability inhibition at 100 μM after 48h).
  • Evidence of programmed cell death activation, including DNA fragmentation and caspase-3 activation, was observed.
  • Limonoids down-regulated Akt, inhibited androgen receptor signaling, and modulated cell cycle proteins, indicating multi-pathway cytotoxicity.

Conclusions:

  • Obacunone and OG exhibit potent cytotoxic effects on androgen-dependent prostate cancer cells.
  • These natural compounds induce apoptosis and inhibit cancer progression via multiple molecular mechanisms.
  • This study provides the first evidence of obacunone and OG's efficacy against human prostate cancer cells.
Keywords:
Cell signalCitrusInflammationLNCaP cellsLimonoidsProgrammed cell deathProstate-specific antigen

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