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Anand et al. J Cancer Metastasis Treat 2019;5:6 Journal of Cancer
DOI: 10.20517/2394-4722.2018.98 Metastasis and Treatment

Original Article Open Access

A non-toxic approach for treatment of breast
cancer and its metastases: capecitabine enhanced

photodynamic therapy in a murine breast tumor
model

Sanjay Anand 1,2,3 , Anton Yasinchak , Taylor Bullock , Mukul Govande , Edward V. Maytin 1,2,3
1
3
1
1 Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
2 Institute of Plastic Surgery and Dermatology, Cleveland Clinic, Cleveland, OH 44195, USA.
3 Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Correspondence to: Dr. Sanjay Anand, Edward V. Maytin, Department of Biomedical Engineering, Lerner Research Institute,
Cleveland Clinic, ND-20, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Email: anands@ccf.org; maytine@ccf.org
How to cite this article: Anand S, Yasinchak A, Bullock T, Govande M, Maytin EV. A non-toxic approach for treatment of breast
cancer and its metastases: capecitabine enhanced photodynamic therapy in a murine breast tumor model. J Cancer Metastasis
Treat 2019;5:6. http://dx.doi.org/10.20517/2394-4722.2018.98

Received: 11 Dec 2018 Accepted: 4 Jan 2019 Published: 24 Jan 2019
Science Editor: William P. Schiemann Copy Editor: Cui Yu Production Editor: Huan-Liang Wu

Abstract
Aim: Breast cancer (BCA) in women is a leading cause of mortality and morbidity; distant metastases occur
in ~40% of cases. Here, as an alternative to ionizing radiation therapy and chemotherapy and their associated
side effects, we explored a new combination approach using capecitabine (CPBN) and aminolevulinate-based
photodynamic therapy (PDT). We had previously developed a combination PDT approach in which 5-fluorouracil
(5FU), a differentiation-promoting agent, increases the levels of protoporphyrin IX (PpIX) in cancer cells when
given as a neoadjuvant prior to aminolevulinic acid (ALA). However, 5FU can be toxic when administered
systemically at high levels. We reasoned that CPBN, a known chemotherapeutic for BCA and less toxic than
5FU (because CPBN is metabolized to 5FU specifically within tumor tissues), might work equally well as a PDT
neoadjuvant.

Methods: Murine 4T1 BCA cells harboring a luciferase transgene were injected into breast fat pads of female
nude mice. CPBN (600 mg/kg/day) was administered by oral gavage for 3 days followed by intraperitoneal
ALA administration and PDT with red light (633 nm) on day 4. Tumor growth and regression were monitored in
vivo using bioluminescence imaging. Histological changes in primary tumors and metastases were assessed by
immunohistochemistry after necropsy.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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