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Photodynamic treatment with purpurin 18 effectively inhibits triple negative breast cancer by inducing cell apoptosis

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Abstract

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.

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Funding

This 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).

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Authors and Affiliations

  1. School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong

    Pengyun Huang, Baoting Zhang, Qiuju Yuan, Xie Zhang & Chuanshan Xu

  2. Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China

    Pengyun Huang & Chuanshan Xu

  3. Asia-Pacific Institute of Aging Studies, Lingnan University, Tuen Mun, Hong Kong

    Wingnang Leung

  4. Key Laboratory of Molecular Target and Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China

    Chuanshan Xu

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  1. Pengyun Huang
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  2. Baoting Zhang
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  3. Qiuju Yuan
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  4. Xie Zhang
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  5. Wingnang Leung
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  6. Chuanshan Xu
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Corresponding authors

Correspondence to Wingnang Leung or Chuanshan Xu.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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).

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Huang, P., Zhang, B., Yuan, Q. et al. Photodynamic treatment with purpurin 18 effectively inhibits triple negative breast cancer by inducing cell apoptosis. Lasers Med Sci 36, 339–347 (2021). https://doi.org/10.1007/s10103-020-03035-w

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  • DOI: https://doi.org/10.1007/s10103-020-03035-w

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