We have reported that photodynamic therapy (PDT) using the photosensitizer phthalocyanine (Pc) 4 and red light damages the antiapoptotic protein Bcl-2. Recently, using transient transfection of Bcl-2 deletion mutants, we identified the membrane anchorage domains of Bcl-2 as necessary to form the photosensitive target. However, it is not clear how Bcl-2 photodamage sensitizes cells to Pc 4-PDT-induced apoptosis, whether overall cell killing is also sensitized or how up-regulation of Bcl-2 in tumors might make them more or less responsive to Pc 4-PDT. In this study we report on MCF-7c3 cells (human breast cancer cells expressing stably transfected procaspase-3) overexpressing wild-type Bcl-2 or certain deletion mutants in either a transient or a stable mode. By flow cytometric analysis of transiently transfected cells, we found that wild-type Bcl-2, Bcl-2delta33-54 and Bcl-2delta37-63 (each of which can be photodamaged) protected cells from apoptosis caused by Pc 4-PDT. In contrast, Bcl-2delta210-239, which lacks the C-terminal transmembrane domain and cannot be photodamaged, afforded no protection. We then evaluated the PDT sensitivity of transfected cell lines stably overexpressing high levels of wild-type Bcl-2 or one of the Bcl-2 mutants. Overexpression of wild-type Bcl-2, Bcl-2delta33-54 or Bcl-2delta37-63 resulted in relative resistance of cells to Pc 4-PDT, as assessed by morphological apoptosis or loss of clonogenicity. Furthermore, overexpression of Bcl-2 also inhibited the activation-associated conformational change of the proapoptotic protein Bax, and higher doses of Pc 4 and light were required to activate Bax in cells expressing high levels of Bcl-2. Many advanced cancer cells have elevated amounts of Bcl-2. Our results show that increasing the dose of Pc 4-PDT can overcome the resistance afforded by either Bcl-2 or the two mutants. PDT regimens that photodamage Bcl-2 lead to activation of Bax, induction of apoptosis and elimination of the otherwise resistant tumor cells.
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Sci Rep
January 2025
Faculty of Biotechnology, October University for Modern Sciences and Arts, 6th of October, Egypt.
Calcium hydroxide nanoparticles (Ca(OH)NPs) possess potent antimicrobial activities and unique physical and chemical properties, making them valuable across various fields. However, limited information exists regarding their effects on genomic DNA integrity and their potential to induce apoptosis in normal and cancerous human cell lines. This study thus aimed to evaluate the impact of Ca(OH)NPs on cell viability, genomic DNA integrity, and oxidative stress induction in human normal skin fibroblasts (HSF) and cancerous hepatic (HepG2) cells.
View Article and Find Full Text PDFDev Comp Immunol
January 2025
Department of Marine Life Sciences & Center for Genomic Selection in Korean Aquaculture, Jeju National University, Jeju 63243, Republic of Korea; Marine Life Research Institute, Jeju National University, Jeju 63333, Republic of Korea. Electronic address:
Interferon regulatory factor 2 (IRF2) is a member of the IRF family that is specifically involved in diverse immune responses via interferon (IFN)/IRF-dependent signaling pathways. In this study, IRF2 of Epinephelus akaara (EAIRF2) was identified and characterized by evaluating its structural and functional properties. EAIRF2 showed the highest homology with IRF2 of Epinephelus coioides and clustered with teleosts in the phylogenetic tree.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Department of Parasitology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Background: Intestinal larva invasion is a crucial step of Trichinella spiralis infection. Intestinal infective larvae (IIL) and their excretory/secretory proteins (ESP) interact with gut epithelium, which often results in gut epithelium barrier injuries. Previous studies showed when T.
View Article and Find Full Text PDFDokl Biochem Biophys
January 2025
Affiliated Hospital of Hebei University, 071000, Baoding City, Hebei Province, China.
Unlabelled: . Renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is the primary malignancy affecting the genitourinary system. It represents the majority of kidney cancer cases and is distinguished by its aggressive nature and high mortality rate.
View Article and Find Full Text PDFDokl Biochem Biophys
January 2025
Department of Biophysics, Faculty of Medicine, Van Yuzuncu Yil University, Van, Türkiye.
Laryngeal squamous cell carcinoma is a common type of head and neck cancer. This study investigated the role of the TRPM2 channel in doxorubicin (DOX)-induced cell damage in human laryngeal squamous cancer cells (Hep-2). Cells were exposed to various DOX concentrations and the appropriate dose was found.
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