This study aims to evaluate the photodynamic efficacy of purpurin 18 (pu-18) on triple negative breast cancer both in vitro and in vivo. Two states of 4T1 cells, 2D culture and 3D spheroids, were used to evaluate the photodynamic action of pu-18 in vitro. The in vitro study results indicated that for the 4T1 2D cell culture, the photodynamic therapy (PDT) treatment showed significant photocytotoxicity at low pu-18 concentrations following light irradiation. Pu-18 was found to distribute on the lysosomes, mitochondria, Golgi apparatus, and endoplasmic reticulum. After irradiation, pu-18 can generate ROS to destroy the mitochondrial membrane potential (MMP) and eventually induce apoptosis in the 2D 4T1 cells. Light-activated pu-18 could also induce the destruction of the 3D 4T1 cell spheroids. The in vivo study was conducted by using a subcutaneous 4T1 breast cancer animal model. The results demonstrated that pu-18 could remain in the tumor for more than 4 days by direct intra-tumoral injection. The PDT treatment was performed every 2 days for a total of 3 times. The results showed that PDT treatment could significantly inhibit tumor growth in vivo, indicating a good photodynamic efficacy of pu-18 in the mouse breast cancer model, without influencing weight and major organ function. The survival pattern results showed that PDT treatment could largely extend the survival time of mice with breast cancer. The preliminary conclusion is that photodynamic treatment using pu-18 is effective at preventing the growth of triple negative breast cancer cells both in vitro and in vivo. A combination of light irradiation and pu-18 could therefore be a worthwhile approach for the treatment of triple negative breast cancer.
Bibliographical noteThis work was supported by Health and Medical Research Fund (13120442 and 12110442), the general research fund (GRF) grant from Hong Kong research grant committee (476912), and Innovation and Technology Fund of Shenzhen (JCYJ20170307165459562).
This study was approved by both the Department of Health, The Government of the Hong Kong Special Administrative Region (Ref. No. (17-679) in DH/SHS/8/2/1 Pt.6.), and the Animal Experimentation Ethic Committee of The Chinese University of Hong Kong (Ref No. 18-188-MIS).
- Purpurin 18
- Triple negative breast cancer
- Photodynamic therapy
- Mitochondrial membrane potential
- Survival time
- Tumor Burden/drug effects
- Body Weight/drug effects
- Optical Imaging
- Spheroids, Cellular/drug effects
- Apoptosis/drug effects
- Photosensitizing Agents/pharmacology
- Subcellular Fractions/metabolism
- Membrane Potential, Mitochondrial/drug effects
- Triple Negative Breast Neoplasms/drug therapy
- Mitochondria/drug effects
- Cell Line, Tumor
- Mice, Inbred BALB C