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PV-10 triggers immunogenic cell death in head and neck squamous cell carcinoma via endoplasmic reticulum stress and apoptosis

ABSTRACT: Primary risk factors of head and neck squamous cell carcinoma (HNSCC) include human papillomavirus (HPV) infection and exposure to tobacco and excessive alcohol. Despite currently available treatments, patients with recurrent HNSCC still have poor survival, highlighting the need for innovative therapies. PV-10, also known as rose bengal sodium (RBS, 4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein disodium), is a small molecule being developed as an intralesional (IL) therapeutic agent, exhibiting substantial anti-tumor activity across diverse cancer types, but current knowledge regarding the molecular mechanisms involved in response to PV-10 remains limited. We evaluated the cytotoxic effects of PV-10 in HNSCC and explored its molecular mechanisms. In vitro, we found that PV-10 induced cytotoxicity in mEER and MTE-RAS cell lines, primarily by increasing the production of reactive oxygen species and leading to apoptosis through a caspase-dependent mechanism. Additionally, we observed that PV-10 treatment increased the release of damage-associated molecular pattern molecules such as HMGB1 and ATP and enhanced expression of calreticulin, HSP-70, and HSP-90 indicating potent immunogenic cell death (ICD). In vivo, IL PV-10 injections led to significant tumor regression in both mEER and MTE-Ras models. Complete responses (CR) were observed in 7 of 21 (33%) mice in mEER although no CR was observed in MTE-Ras. Our data suggests that one of the possible mechanisms by which PV-10 triggers ICD is by inducing endoplasmic reticulum stress, autophagy, and apoptosis. Our findings contribute to further understanding of the underlying mechanisms of PV-10 induced cytotoxicity and to develop future clinical trials in locally recurrent HNSCC.

ORGANISM(S): Mus musculus

PROVIDER: GSE289911 | GEO | 2025/08/13

REPOSITORIES: GEO

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PV-10 triggers immunogenic cell death in head and neck squamous cell carcinoma via endoplasmic reticulum stress and apoptosis

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