Cardamonin reduces chemotherapy-enriched breast cancer stem-like cells<i>in vitro</i>and<i>in vivo</i>
Bibliographic record
Abstract
// Deyong Jia 1 , Yuan Tan 1 , Huijuan Liu 1, 2 , Sarah Ooi 1 , Li Li 1 , Kathryn Wright 1 , Steffany Bennett 1 , Christina L. Addison 1, 3 , Lisheng Wang 1, 4, 5 1 Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada 2 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200240, China 3 Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada 4 Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada 5 Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada Correspondence to: Lisheng Wang, e-mail: lwang@uottawa.ca Keywords: chemotherapy, cardamonin, breast cancer stem cells, in vivo Received: April 24, 2015 Accepted: October 06, 2015 Published: October 17, 2015 ABSTRACT The failure of cytotoxic chemotherapy in breast cancers has been closely associated with the presence of drug resistant cancer stem cells (CSCs). Thus, screening for small molecules that selectively inhibit growth of CSCs may offer great promise for cancer control, particularly in combination with chemotherapy. In this report, we provide the first demonstration that cardamonin, a small molecule, selectively inhibits breast CSCs that have been enriched by chemotherapeutic drugs. In addition, cardamonin also sufficiently prevents the enrichment of CSCs when simultaneously used with chemotherapeutic drugs. Specifically, cardamonin effectively abolishes chemotherapeutic drug-induced up-regulation of IL-6, IL-8 and MCP-1 and activation of NF-κB/IKBα and Stat3. Furthermore, in a xenograft mouse model, co-administration of cardamonin and the chemotherapeutic drug doxorubicin significantly retards tumor growth and simultaneously decreases CSC pools in vivo . Since cardamonin has been found in some herbs, this work suggests a potential new approach for the effective treatment of breast CSCs by administration of cardamonin either concurrent with or after chemotherapeutic drugs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".