Saponin Facilitates Anti-Robo1 Immunotoxin Cytotoxic Effects on Maxillary Sinus Squamous Cell Carcinoma

Komatsu, Noriko; Komatsu, Miku; Ohashi, Riuko; Horii, Akira; Hoshi, Kazuto; Takato, Tsuyoshi; Abe, Takahiro; Hamakubo, Takao

doi:10.1155/2020/9593516

Cited by 5 publications

(12 citation statements)

References 35 publications

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“…One explanation for this result is that the fish culture cell lines used in our study may be more sensitive to the action of saponins, an issue to look into in future in vitro studies using fish cells lines. The toxicity in the fish cell line used here was very similar to those observed in vitro, conducted using quillaja saponin extracts on human gastric cancer cells lines SNU1 and KATO III [70], and human maxillary sinus squamous cancer cell lines HNSCC [71] showed similar toxicity results (13 to 67 µg/mL). These results suggest that cancer cell lines may have changed the structure of the cell membrane, as supported by previous studies [72].…”

Section: Discussionsupporting

confidence: 78%

Quillaja saponaria (Molina) Extracts Inhibits In Vitro Piscirickettsia salmonis Infections

Cañon–Jones

Cortés

Castillo–Ruiz

et al. 2020

Animals

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P. salmonis infections are the cause of major bacterial disease in salmonids in Chile, and the reason for using more antibiotics compared to other salmon-producing countries. Vaccination and antibiotics have not been efficient and new approaches are needed. The safety of Quillaja saponaria extracts was measured by cytotoxicity using flow cytometry of cytopathic and death of fish cell cultures and efficacy was assessed using in vitro infection models with pathogenic P. salmonis. Cytotoxicity was low and control of in vitro infections was achieved with all products, with protection of over 90%. Minimum inhibitory concentrations were much higher than those in the infection using cell cultures. These results suggest a dual mechanism of action where less purified extracts with a combination of saponin and non-saponin components simultaneously decrease P. salmonis infection while protecting cell lines, rather than exerting a direct antimicrobial effect. Quillaja saponins controlled in vitro infections with P. salmonis and could be considered good candidates for a new, safe and sustainable method of controlling fish bacterial infectious diseases.

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Section: Discussionsupporting

confidence: 78%

Quillaja saponaria (Molina) Extracts Inhibits In Vitro Piscirickettsia salmonis Infections

Cañon–Jones

Cortés

Castillo–Ruiz

et al. 2020

Animals

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“…Since photosensitizer administration and light exposure enhanced the cytotoxic effect of IT-ROBO1 enormously, we concluded that the cytotoxicity results from the problem of endosomal escape (10,11,18). This was also supported by our observation that treatment with saponin, which facilitates the internalization of IT, and the endosomal release of saporin, augmented cytotoxicity and enhanced the tumor-reducing effect both in vitro and in vivo (24).…”

Section: Discussionsupporting

confidence: 64%

“…It was subsequently reported that ROBO1 is specifically expressed in a wide range of malignant cells or neoangiogenic endothelial cells (21,22). Thus, ROBO1 has been widely studied as a good molecular target for cancer therapy (7,8,14,16,18,(21)(22)(23)(24). Maiti et al reported the expression of ROBO1 in HNSCC (23).…”

Section: Discussionmentioning

confidence: 99%

Photosensitizer With Illumination Enhances In Vivo Antitumor Effect of Anti-ROBO1 Immunotoxin on Maxillary Sinus Squamous Cell Carcinoma

Komatsu

Ohashi

et al. 2020

Anticancer Res

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Background/Aim: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer worldwide. Our study focused on the axon guidance receptor roundabout guidance receptor 1 (ROBO1) as a target for monoclonal antibody therapy of HNSCC. We previously showed that saporin-conjugated anti-ROBO1 (B5209B) immunotoxin (IT-ROBO1) enhanced cytotoxic effects on HNSCC cells in combination with the photosensitizer aluminum phthalocyanine disulphonate (AlPcS2a) and illumination. We examined the effects of this combination therapy in a mouse xenograft model. Materials and Methods: IT-ROBO1 was intraperitoneally administered to HSQ-89 (derived from Japanese maxillary sinus squamous carcinoma, RCB0789; RIKEN, Tsukuba, Japan) xenografted mice. After 3 days, AlPcS2a was injected subcutaneously around the tumor and the area was illuminated at 650 nm for 30 min. The growth of the tumor was evaluated and the effects on the tumor were examined. Results: Pronounced anti-tumor effects were elicited by the administration of IT-ROBO1 and AlPcS2a with light illumination on tumor size and pathological characteristics. Conclusion: The results showed that photosensitizer treatment with illumination robustly enhanced the antitumor effect of the IT-ROBO1 immunotoxin.The annual number of deaths from head and neck cancer worldwide was recently reported to be 300,000 (1, 2). Triple therapy has been the standard treatment for Head and neck squamous cell carcinoma (HNSCC), i.e. the combination of surgery, radiation therapy and chemotherapy. Various complications, however, such as postoperative aesthetic issues, masticatory disorders, dysphagia, articulatory disorders, respiratory disorders, mucositis, and long-term osteomyelitis have been matters of concern with regard to quality of life. As the number of patients suffering from HNSCC is increasing with the aging of society, the development of new treatments with less functional impairment and higher therapeutic effect is an urgent issue.Monoclonal antibody treatment is one of the approaches expected to afford improved care. Cetuximab and nivolumab have been approved for HNSCC treatment by the Food and Drug Administration (FDA) (3). Several methods to enhance antitumor effects have been tried, such as antibody drug conjugates, immunotoxin (IT), and radioimmunotherapy (RIT) (4). Trastuzumab-emtansine as an antibody drug conjugate was approved for inoperable or recurrent breast cancer that is human epidermal growth factor receptor 2 (HER2)-positive by the FDA in 1988 (5). IT was also approved for CD25-positive T-cell lymphoma (6) by the FDA in 2019. We demonstrated that a radioactive antibody 3793

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“…This molecule does not have a natural cell‐binding domain and is active only when transferred to the cytosol after endocytosis. 18 , 19 The antitumor principle of the iTAP method involves a high concentration of saporin delivered to cancer cells, specifically by cetuximab, which accumulates in endosomes. Subsequently, on laser irradiation of NPe6, the photodynamic effect causes saporin to translocate from the endosome to the cytosol, leading to cell death.…”

Section: Introductionmentioning

confidence: 99%

“…Saporin is a toxic protein with a molecular weight of ~30 kDa and is classified as a type 1 ribosome‐inactivating protein (RIP) isolated from the plant Saponaria officinalis . This molecule does not have a natural cell‐binding domain and is active only when transferred to the cytosol after endocytosis 18,19 . The antitumor principle of the iTAP method involves a high concentration of saporin delivered to cancer cells, specifically by cetuximab, which accumulates in endosomes.…”

Section: Introductionmentioning

confidence: 99%

Development of a new minimally invasive phototherapy for lung cancer using antibody–toxin conjugate

Sonokawa

Obi²,

Usuda

et al. 2023

Thoracic Cancer

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Background Photodynamic therapy (PDT) is a cancer‐targeted treatment that uses a photosensitizer (PS) and laser irradiation. The effectiveness of current PDT using red light for advanced cancers is limited, because red light can only reach depths within a few millimeters. To enhance the antitumor effect for lung cancers, we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin and a PS, mono‐L‐aspartyl chlorin e6 (NPe6). Methods We examined whether cetuximab encapsulated in endosomes was released into the cytosol by PS in PDT under light irradiation. A431 cells were treated with fluorescein isothiocyanate‐labeled cetuximab, NPe6, and light irradiation and were observed with fluorescence microscopy. We analyzed the cytotoxicity of saporin‐conjugated cetuximab (IT‐cetuximab) in A431, A549, and MCF7 cells and the antitumor effect in model A549‐bearing mice in vivo using the iTAP method. Results Fluorescent microscopy analysis showed that the photodynamic effect of NPe6 (20 μM) and light irradiation (37.6 J/cm 2 ) caused the release of cetuximab from the endosome into the cytosol. In vitro analysis demonstrated that the iTAP method enhanced the cytotoxicity of IT‐cetuximab by the photodynamic effect. In in vivo experiments, compared with IT‐cetuximab alone or PDT alone, the iTAP method using a low dose of IT‐cetuximab showed the greatest enhancement of the antitumor effect. Conclusions Our study is the first report of the iTAP method using NPe6 for lung cancer cells. The iTAP method may become a new, minimally invasive treatment superior to current PDT methods.

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Saponin Facilitates Anti-Robo1 Immunotoxin Cytotoxic Effects on Maxillary Sinus Squamous Cell Carcinoma

Cited by 5 publications

References 35 publications

Quillaja saponaria (Molina) Extracts Inhibits In Vitro Piscirickettsia salmonis Infections

Quillaja saponaria (Molina) Extracts Inhibits In Vitro Piscirickettsia salmonis Infections

Photosensitizer With Illumination Enhances In Vivo Antitumor Effect of Anti-ROBO1 Immunotoxin on Maxillary Sinus Squamous Cell Carcinoma

Development of a new minimally invasive phototherapy for lung cancer using antibody–toxin conjugate

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