Triptolide: An inhibitor of a disintegrin and metalloproteinase 10 (ADAM10) in cancer cells
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Triptolide, a diterpene triepoxide derived from Trypterygium wilfordii, is documented to have antitumor activity in a broad range of solid tumors and leukemia. The mechanisms that are involved in triptolide-mediated apoptosis or growth inhibition in cancer cells are not fully understood. We identified a disintegrin and metalloproteinase 10 (ADAM10) as a novel molecular target of triptolide using affinity chromatography and mass spectrometry. The identification was confirmed by western blot analysis using an anti-ADAM10 antibody. The expression of ADAM10 is enhanced in several tumors including leukemia and is involved in malignant cell growth and cancer progression. ADAM10 is a type 1 transmembrane glycoprotein that cleaves several plasma membrane proteins. We show that triptolide, at concentrations in the nM range, resulted in a significant decrease in ADAM10 expression followed by the appearance of ADAM10 cleaved product. Furthermore, triptolide reduced the viability of monocytic leukemic U937 cells. Triptolide treatment of MCF-7 breast cancer cells expressing ectopic ADAM10 or dominant negative ADAM10 (DN ADAM10) resulted in a decreased expression of ADAM10 with a concomitant increase in ADAM10 cleaved products. Moreover, siRNA-mediated knockdown of ADAM10 mRNA significantly affected the growth of MCF-7 cells. Interestingly, the combination of siRNA-mediated knockdown of ADAM10 mRNA expression and triptolide treatment lead to a further reduction in cell growth. Taken together, we provide evidence that ADAM10 is a novel target of triptolide, presenting a novel strategy to inhibit ADAM10 activity in tumorigenesis.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 it