ArticleInternational journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group2025
The efficacy of hyperthermia-based multimodal therapy is dependent on gatekeeper protein, BID.
Article in International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Tumoricidal Efficacy of Artesunate-Eluting Microsphere-Based Multimodal Therapy in Patient-Derived Colorectal Tumoroids.Biomaterials research · 2026Article
- DZ-1-artesunate conjugate induces mitochondria-mediated, reactive oxygen species-dependent apoptosis in colorectal cancer tumoroids.Frontiers in pharmacology · 2026Article
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4 authors.
Funding
Abstract
objectivesThe combination of ferroptotic agent artesunate (ART) and apoptotic agent rhTRAIL (recombinant human tumor necrosis factor-related apoptosis-inducing ligand) has been shown to synergistically enhance apoptosis in various cancer cell lines via crosstalk between the endoplasmic reticulum (ER) stress response, the rhTRAIL-induced extrinsic cell death receptor pathway, and the intrinsic BID-Bax-mitochondrial-dependent-apoptosis pathway. This synergistic interaction has been demonstrated to be effective in multiple types of cancer cell lines, making artesunate combined with rhTRAIL a promising second-line therapy for colon cancer patients after cytoreductive surgery and chemotherapeutic treatments. To further enhance the second-line therapy's tumoricidal effect, a multimodal therapy was developed by combining artesunate, rhTRAIL, and hyperthermic conditions where samples were treated at 42 °C for 1 h.
methodsThe effects of this therapy were tested in human colon carcinoma HCT116 and pancreatic adenocarcinoma BxPC-3 cell models. The cytotoxic and synergistic effects were analyzed using fluorescence microscopy, cell survival assays, and protein analysis through Western blotting.
resultsOur findings demonstrated a significant enhancement of apoptosis when artesunate and rhTRAIL treatments were combined with heat exposure. The synergistic and apoptotic effect of the agents was effectively abrogated in BID-deficient and BID mutant-type cells as well as Bax-deficient cells, but not Bak-deficient cells.
conclusionsThe results suggest that BID acts as a key gatekeeper molecule of apoptosis during hyperthermia-based multimodal treatment. These findings raise important questions about the underlying mechanisms of heat-induced apoptosis and its involvement in orchestrating various cellular stress pathways.
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