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Dihydrotanshinone I induced apoptosis and autophagy through caspase dependent pathway in colon cancer

Lin Wang1, Tao Hu1, Jing Shen1

  • 1School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Lo Kwee-Seong Integrated Biomedical Sciences Building, Shatin, NT, Hong Kong, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|November 9, 2015
PubMed
Abstract

Insights

Dihydrotanshinone I (DHTS) effectively combats colon cancer by triggering apoptosis and autophagy through mitochondria. This natural compound shows promise as a novel anti-tumor agent or adjuvant therapy.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • Dihydrotanshinone I (DHTS) demonstrates potent anti-cancer activity in colon cancer cells.
  • Its cytotoxic effects are dependent on reactive oxygen species (ROS) but independent of p53.

Purpose of the Study:

  • To investigate the anti-cancer effects of DHTS in colon cancer.
  • To elucidate the molecular mechanisms underlying DHTS action in vitro and in vivo.

Main Methods:

  • Assessed caspase activity, apoptosis (flow cytometry, TUNEL assay), and protein levels (western blotting).
  • Utilized siRNA for gene knockdown and confocal microscopy for LC3B puncta and caspase-3 activation.
  • Evaluated in vivo anti-colon cancer activity in xenograft mouse models.

Main Results:

  • DHTS exhibited anti-colon cancer activity by inducing apoptosis and autophagy both in vitro and in vivo.
  • Mitochondria-mediated, caspase-dependent pathways were crucial for DHTS-induced cytotoxicity.
  • Apoptosis was modulated by AIF, caspase-3/9, and caspase-2, with observed crosstalk between cytochrome c and AIF.

Conclusions:

  • DHTS induces apoptosis and autophagy via mitochondrial pathways, involving caspases and ROS.
  • DHTS presents potential as a leading compound for anti-tumor drug development or as an adjuvant therapy for colon cancer.
Keywords:
ApoptosisAutophagyCaspaseColon cancerDihydrotanshinone IDihydrotanshinone I (PubChem CID: 11425923)Mitochondria

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