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Sensitization of recombinant human tumor necrosis factor-related apoptosis-inducing ligand-resistant malignant

Katherine A Turner1,2, Jasmine M Manouchehri1,2, Michael Kalafatis1,2,3

  • 1Department of Chemistry, Cleveland State University.

Melanoma Research
|March 30, 2018
PubMed

Insights

Quercetin sensitizes resistant malignant melanomas to recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) therapy. This natural compound enhances cancer cell death by increasing rhTRAIL receptors and degrading survival proteins, offering a new treatment approach.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Malignant melanoma, a common skin cancer, presents a high risk of metastasis.
  • Metastatic melanoma is highly resistant to conventional treatments, leading to poor survival rates.
  • Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) shows promise for melanoma treatment due to its cancer-selective apoptosis induction.

Purpose of the Study:

  • To investigate the potential of quercetin in overcoming rhTRAIL resistance in malignant melanoma.
  • To elucidate the molecular mechanisms by which quercetin sensitizes melanoma cells to rhTRAIL.

Main Methods:

  • Utilized rhTRAIL-resistant melanoma cell lines.
  • Treated cells with quercetin and rhTRAIL, individually and in combination.
  • Assessed cell surface receptor expression (DR4, DR5) and FLIP protein levels via proteasomal degradation assays.

Main Results:

  • Quercetin effectively sensitized rhTRAIL-resistant melanoma cells.
  • Quercetin treatment led to increased expression of rhTRAIL receptors DR4 and DR5.
  • Quercetin promoted the proteasome-mediated degradation of the antiapoptotic protein FLIP.

Conclusions:

  • Quercetin can overcome rhTRAIL resistance in malignant melanoma.
  • The sensitization mechanism involves upregulation of DR4/DR5 and degradation of FLIP.
  • This combination therapy represents a promising, non-toxic treatment strategy for advanced melanoma.

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