α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation

K. M. Abdullah, Gunjan Sharma, Simran Takkar, Jyoti B. Kaushal, Ramesh Pothuraju, Bandana Chakravarti, Surinder Kumar Batra, Jawed A. Siddiqui

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Prostate cancer (PCa) progression leads to bone modulation in approximately 70% of affected men. A nutraceutical, namely, α-lipoic acid (α-LA), is known for its potent anti-cancer properties towards various cancers and has been implicated in treating and promoting bone health. Our study aimed to explore the molecular mechanism behind the role of α-LA as therapeutics in preventing PCa and its associated bone modulation. Notably, α-LA treatment significantly reduced the cell viability, migration, and invasion of PCa cell lines in a dose-dependent manner. In addition, α-LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF-1α expression, which started the downstream molecular cascade and activated JNK/caspase-3 signaling pathway. Flow cytometry data revealed the arrest of the cell cycle in the S-phase, which has led to apoptosis of PCa cells. Furthermore, the results of ALP (Alkaline phosphatase) and TRAP (tartrate-resistant acid phosphatase) staining signifies that α-LA supplementation diminished the PCa-mediated differentiation of osteoblasts and osteoclasts, respectively, in the MC3T3-E1 and bone marrow macrophages (BMMs) cells. In summary, α-LA supplementation enhanced cellular apoptosis via increased ROS levels, HIF-1α expression, and JNK/caspase-3 signaling pathway in advanced human PCa cell lines. Also, the treatment of α-LA improved bone health by reducing PCa-mediated bone cell modulation.

Original languageEnglish (US)
Article number4404
JournalScientific reports
Volume14
Issue number1
DOIs
StatePublished - Dec 2024

Keywords

  • Bone modulation
  • HIF-1α
  • Osteoblasts
  • Osteoclasts
  • p-JNK
  • Prostate cancer
  • Reactive oxygen species (ROS)
  • α-LA

ASJC Scopus subject areas

  • General

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