Abstract
Photodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a suitable wavelength. In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours. Photodynamic therapy mediated by parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT, *p < 0.0001, ANOVA test followed by Tukey’s multiple comparisons test), suggesting that both PTN and PTN-PDT would be potential inhibitors of metastasis. Fluorescence microscopy observation indicated cytoplasmic localization of the AQ and no fluorescence at all was recorded in the nuclei. When PTN (1.96 mg) dissolved in dimethyl sulfoxide was topically applied on the skin of mice subcutaneously implanted with LM2 cells, PTN orange fluorescence was strongly noticed in the stratum corneum and also in the inner layers of the tumour up to approximately 5 mm. After illumination with 12.74 J/cm2 of blue light, one PDT dose at day 1, induced a significant tumour growth delay at day 3, which was not maintained in time. Therefore, we administered a second PTN-PDT boost on day 3. Under these conditions, the delay of tumour growth was 28% both on days 3 and 4 of the experiment (*p < 0.05 control vs. PTN-PDT, two-way ANOVA, followed by Sidak’s multiple comparisons test). Histology of tumours revealed massive tumour necrosis up to 4 mm of depth. Intriguingly, a superficial area of viable tumour in the 1 mm superficial area, and a quite conserved intact skin was evidenced. We hypothesize that this may be due to PTN aggregation in contact with the skin and tumour milieu of the most superficial tumour layers, thus avoiding its photochemical properties. On the other hand, normal skin treated with PTN-PDT exhibited slight histological changes. These preliminary findings encourage further studies of natural AQs administered in different vehicles, for topical treatment of cutaneous malignancies.
Highlights
Photodynamic therapy (PDT) is an anticancer treatment involving the administration of a tumor-localizing photosensitizer (PS), followed by activation by light at its absorption wavelength
Some intercalating AQs have been employed systemically for cancer treatment[11], to the best of our knowledge there are no reports of AQs employed in topical use for superficial tumours
Natural AQs such as emodin, which is an AQ derivative isolated from the roots of Rheum officinale Baill, was topically administrated to rats in a hydrogel containing 2% carbopol for the treatment of skin w ounds[33]
Summary
Photodynamic therapy (PDT) is an anticancer treatment involving the administration of a tumor-localizing photosensitizer (PS), followed by activation by light at its absorption wavelength. PDT mediated by 5-aminolevulinic acid, has a superior cosmetic outcome as compared to other forms of treatment such as curettage, freezing and other ablative techniques, and indications such as actinic keratoses, Bowen’s disease and basal cell carcinomas have been approved many years ago[4,5]. Even though PDT has been investigated for decades, only few PSs are approved for use in a clinical s etting[6]. Porphyrins, phthalocyanines and chlorophyll derivatives have been approved for clinical use; new PSs bearing higher selectivity and fewer dark toxicity are desirable
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
