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Melatonin and 5-fluorouracil co-suppress colon cancer stem cells by regulating cellular prion protein-Oct4 axis

Jun Hee Lee1, Chul Won Yun2, Yong-Seok Han2

  • 1Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.

Journal of Pineal Research
|August 10, 2018
PubMed

Insights

Melatonin inhibits colon cancer stem cells by regulating the cellular prion protein (PrPC) and Oct4. This suggests a new therapeutic strategy combining melatonin with chemotherapy for colorectal cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Melatonin is known to suppress tumor development, but its precise role in cancer stem cells (CSCs) remains unclear.
  • Colorectal cancer (CRC) progression is linked to cancer stemness, highlighting the need for targeted therapies.

Purpose of the Study:

  • To investigate the effect of melatonin on colon CSCs and elucidate the underlying molecular mechanisms.
  • To explore the correlation between cellular prion protein (PrPC) and Oct4 expression with CRC metastasis and tumor stage.

Main Methods:

  • Analysis of PrPC and Oct4 expression in CRC patient specimens.
  • In vitro studies using colorectal CSCs treated with melatonin, 5-fluorouracil (5-FU), or combination therapy.
  • Assessment of stem cell markers (Oct4, Nanog, Sox2, ALDH1A1), tumor growth, proliferation, and angiogenesis.

Main Results:

  • Melatonin inhibits colon CSCs by regulating the PrPC-Oct4 axis.
  • PrPC and Oct4 expression levels correlate with CRC metastasis and tumor stage.
  • Combined 5-FU and melatonin treatment downregulated PrPC, inhibiting stem cell markers, tumor growth, proliferation, and angiogenesis.
  • PRNP overexpression in colorectal CSCs protected Oct4, but not Nanog, Sox2, or ALDH1A1, from 5-FU and melatonin inhibition.

Conclusions:

  • PrPC directly regulates Oct4 and indirectly influences Nanog, Sox2, and ALDH1A1, maintaining cancer stemness in CRC.
  • Targeting the PrPC-Oct4 axis presents a promising therapeutic strategy for colorectal cancer.
  • Combination therapy with anticancer drugs and melatonin offers a potential treatment approach for CRC.
Keywords:
Oct4cancer stem cellcellular prion proteinmelatonin

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