Pharmacological interactions of jadomycin B with topoisomerase poisons in MDA-MB-231 human breast cancer cells
Bibliographic record
Abstract
Jadomycin B, a natural product isolated from Streptomyces venezuelae, exerts an anti-cancer effect on human triple negative breast cancer cells in vitro and has anti-tumoral effects in vivo in animal models of breast cancer. One proposed mechanism for this anti-cancer effect is through interaction with topoisomerase 2 (TOP2). Based on the previously described interactions between jadomycin B and TOP2 we hypothesized that jadomycin B will act additively with TOP2 poisons and produce a similar functional outcome in eliciting cell cycle arrest. Combined treatments of jadomycin B and the TOP2 poisons doxorubicin or mitoxantrone produced moderately synergistic to additive cytotoxicity (combination index values ranging from 0.72–0.94) in MDA-MB-231 cells. In comparison, combined mitoxantrone and doxorubicin produced additive cytotoxicity (combination index values 0.96–1.11). Jadomycin B combined with the proteosome inhibitor MG132 had additive cytotoxicity (combination index values 0.76–1.18). In contrast, mitoxantrone or doxorubicin cytotoxicity was antagonized by MG132 (combination index values 1.21–2.31). Jadomycin B treatment arrested cells in S-phase ( P = 0.0024) as opposed to mitoxantrone which caused G 2 /M-phase arrest ( P < 0.0001). In conclusion, jadomycin B interacts differently than known TOP2 poisons in combination, supporting a novel pharmacological mechanism(s) of action for jadomycin B cytotoxicity.
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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 | 0.000 | 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 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".