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Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT-tamoxifen hybrid therapy

Theodossis A Theodossiou1, Muhammad Ali2, Mantas Grigalavicius1

  • 11Department of Radiation Biology, Institute for Cancer Research, Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway.

NPJ Breast Cancer
|April 18, 2019
PubMed

Insights

A new combination therapy, HYPERTAM, merges hypericin photodynamic therapy (HYP-PDT) with tamoxifen (TAM) chemotherapy. This potent approach shows over 90% cancer cell death and significantly improves survival in preclinical models.

Area of Science:

  • Oncology
  • Biochemistry
  • Pharmacology

Background:

  • Cancer treatment faces challenges due to tumor heterogeneity and the limitations of monotherapies.
  • Combinatorial treatments are needed to overcome resistance and improve efficacy.
  • Previous research indicated hypericin photodynamic therapy (HYP-PDT) inhibits the mitochondrial electron transport chain (ETC), and tamoxifen (TAM) enhances cytotoxicity with ETC inhibitors.

Purpose of the Study:

  • To introduce and evaluate a novel synergistic combinatorial treatment (HYPERTAM) combining TAM chemotherapy and HYP-PDT.
  • To assess HYPERTAM's efficacy in two distinct breast cancer cell lines (MDA-MB-231 and MCF7) with differing metabolic profiles.
  • To investigate the mechanisms of cell death, lipid peroxidation, and metabolic effects of HYPERTAM.

Main Methods:

  • Testing the HYPERTAM treatment in vitro on MDA-MB-231 (triple-negative) and MCF7 (estrogen-receptor-positive) breast cancer cell lines.
  • Analyzing cell death pathways (necrosis, autophagy) and measuring lipid peroxidation levels.
  • Conducting an in vivo pilot study using MDA-MB-231 and MCF7 tumor models in NOD SCID-γ immunocompromised mice.

Main Results:

  • HYPERTAM demonstrated over 90% cytotoxicity in both tested breast cancer cell lines.
  • The treatment induced both necrosis and autophagy, accompanied by high levels of lipid peroxidation.
  • In vivo studies showed significant prolongation of survival in mice bearing either MDA-MB-231 or MCF7 tumors.

Conclusions:

  • HYPERTAM is a potent and synergistic therapeutic modality for cancer treatment.
  • This novel combination therapy shows efficacy across diverse tumor types and metabolic profiles.
  • HYPERTAM holds promise as a foundation for future composite anticancer treatments.

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