H 2 O 2 promotes photodynamic efficacy of TMPyP4 against ovarian cancer in vitro by downregulating HIF-1α expression

• Published in: Biomedicine & pharmacotherapy Vol. 177; p. 117110
• Main Authors: Chen, Kejie, Zhai, Yihui, Wang, Yuanqiu, Xu, Zichuang, Chen, Xiaojian, Zhang, Yixin, Zhou, Zhengyi, Zheng, Xiaohui, Lin, Feng
• Format: Journal Article
• Language: English
• Published: France 01.08.2024
• Subjects: Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; DNA Damage - drug effects; Down-Regulation - drug effects; Female; Humans; Hydrogen Peroxide - pharmacology; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Photochemotherapy - methods; Photosensitizing Agents - pharmacology; Porphyrins - pharmacology; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Tumor Microenvironment - drug effects; PDT; HO; Hypoxia; HIF-1α; TMPyP4; Ovarian cancer
• ISSN: 1950-6007

Photodynamic therapy (PDT), employing photosensitizers to induce formation of reactive oxygen species (ROS) for tumor elimination, is emerging as a promising treatment modality in oncology due to its unique benefits. However, the PDT application in ovarian cancer, the most prevalent and lethal type of gynecological malignancy with a severe hypoxic microenvironment, remains unknown. This study revealed that photosensitizer TMPyP4 exhibited enhanced efficacy under H O stimulation, with minimal change in cytotoxicity compared to TMPyP4 alone. The results showed that H O increased ROS production induced by TMPyP4, leading to exacerbated mitochondrial dysfunction and DNA damage, ultimately inhibiting proliferation and inducing apoptosis in ovarian cancer cells. Mechanistically, H O primarily enhanced the therapeutic efficacy of PDT with TMPyP4 against ovarian cancer cells by degrading HIF-1α, which subsequently modulated the HIF-1 signaling pathway, thereby alleviating the hypoxic environment in ovarian cancer cells. Our findings underscore the therapeutic potential of targeting HIF-1α within the hypoxic microenvironment for PDT in ovarian cancer and propose a novel integrated strategy for PDT treatment of this malignancy in vitro.