Cervical cancer cells (HeLa) response to photodynamic therapy using a zinc phthalocyanine photosensitizer

J Photochem Photobiol B. 2017 Dec:177:32-38. doi: 10.1016/j.jphotobiol.2017.10.004. Epub 2017 Oct 4.

Abstract

Cervical cancer is the most common gynecological malignancy worldwide, and the leading cause of cancer related deaths among females. Conventional treatment for early cervical cancer is radical hysterectomy. In locally advanced cancer the treatment of choice is concurrent chemo radiation. Although such treatment methods show promise, they do have adverse side effects. To minimize these effects, as well as prevent cancer re-occurrence, new treatment methods are being investigated. Photodynamic therapy (PDT) involves the selective uptake of a photosensitizer (PS) by cancer cells, illumination with light of an appropriate wavelength that triggers a photochemical reaction leading to the generation of reactive oxygen and subsequent tumor regression. The effect of PDT on a cervical cancer cell line (HeLa) was assessed by exposing cultured cells to a sulphonated zinc phthalocyanine PS (ZnPcSmix) and irradiating the cells using a 673nm diode laser. The effects were measured using the Trypan blue viability assay, adenosine triphosphate assay (ATP) luminescence assay for proliferation, Lactate Dehydrogenase (LDH) membrane integrity cytotoxicity assay, and fluorescent microscopy to assess PS cellular localization and nuclear damage. Fluorescent microscopy revealed localization of the PS in the cytoplasm and perinuclear region of HeLa cells. PDT treated cellular responses showed dose dependent structural changes, with decreased cell viability and proliferation, as well as considerable membrane damage. Hoechst stained cells also revealed DNA damage in PDT treated cells. The final findings from this study suggest that ZnPcSmix is a promising PS for the PDT treatment of cervical cancer in vitro, where a significant 85% cellular cytotoxicity with only 25% cellular viability was noted in cells which received 1μM ZnPcSmix when an 8J/cm2 fluence was applied.

Keywords: Cervical cancer; Photodynamic therapy; Zinc phthalocyanine.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • DNA Damage / drug effects
  • DNA Damage / radiation effects
  • Female
  • HeLa Cells
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Isoindoles
  • L-Lactate Dehydrogenase / metabolism
  • Lasers, Semiconductor
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Organometallic Compounds / therapeutic use
  • Photochemotherapy
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Zinc Compounds

Substances

  • Indoles
  • Isoindoles
  • Organometallic Compounds
  • Photosensitizing Agents
  • Zinc Compounds
  • Zn(II)-phthalocyanine
  • L-Lactate Dehydrogenase