Gap junction enhances phototoxicity of photodynamic therapy agent 2‐[1‐hexyloxyethyl]‐2‐devinylpyropheophorbide‐a (HPPH)
Bibliographic record
Abstract
BACKGROUND AND OBJECTIVE: It has been reported that 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) effects on antitumor. However, it remains unclear whether gap junction (GJ) acts on phototoxicity of HPPH and which pathways are involved in the process. MATERIALS AND METHODS: We determine the effect of HPPH on cancer cell viability and the apoptosis-associated signaling by cell viability assay, reactive oxygen species (ROS) measurement, and caspase-3 activity assay. RESULTS: Our study uniquely showed that there is a strong correlation between GJ and HPPH-PDT cytotoxicity, that inhibition of GJ function in U87 cells by tetradecanoylphorbol-13-aaetate or carbenoxolone reduces HPPH-PDT cytotoxicity, that and the enhancement of GJ function by retinoid acid in U87 cells increases HPPH-PDT cytotoxicity. We also observed that GJ intercellular communication composed of connexin 32 (Cx32) induced by doxycycline in Hela cells enhances HPPH-PDT phototoxicity. In addition, we indicated that GJ prompts the HPPH-induced apoptosis likely due to the "bystander effect" of passing apoptotic signals between cells, which results in improving the accumulation of ROS, which also amplifies mitochondria depolarization and the activation of caspase-3. CONCLUSION: GJ enhances the efficacy of HPPH-PDT in U87 and Hela; GJ augments ROS production, which enhances the loss of mitochondrial membrane potential and the activation of caspase-3, and increases apoptosis in the tumor cells induced by HPPH-PDT. Our findings provide a basis for further development of GJ as a potential prediction of the efficacy of photodynamic therapy.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".