Aglycone Protopanaxadiol, a ginseng saponin inhibits P-glycoprotein and sensitizes chemotherapy drugs on multidrug resistant cancer cells
Bibliographic record
Abstract
9663 Background:Aglycone Protopanaxadiol (aPPD) is an aglycone derivative of ginseng saponins. Our previous work showed that a natural ginseng product CARESENG™ containing mainly aPPD induced cell apoptosis through various signal pathways including caspases. CARESENG™ also enhances the sensitivity of multidrug resistant cancer cells to various chemotherapy drugs. P-glycoprotein (P-gp, MDR1) is one of the major causes of multidrug resistance of many tumor cells. Blocking the function of P-gp may enhance efficacy of chemotherapy. In the present study, we investigated the possible mechanism of chemosensitizing effect of purified aPPD compound as well as CARESENG™. Methods:Breast cancer cell MCF-7adr and leukemia cell line P388adr, both overexpressing P-gp, were used to test the interaction between the compound and P-gp. Calcein-AM, a P-gp substrate, efflux assay was used to measure function of P-gp. Membrane preparation was also used to measure the ATPase activity of P-gp in the presence of aPPD or verapamil. Results:Our results demonstrated that 70uM aPPD could significantly block P-gp function on both MCF-7adr and P388adr cells showing increased intracellular concentrations of calcein-AM. Furthermore, the maximum effects of aPPD and verapamil on P-gp inhibition was additive when treated together on P388adr cells. On the other hand, aPPD had no effect on ATPase activity of P-gp while verapamil increased it by more than 2-fold. 20uM of aPPD completely reversed P-gp induced drug resistant to Taxol or Doxorubicin on MCF-7adr cells. CARESENG™ gave rise to similar results in all the above experiments. Conclusions: These results suggest that aPPD is an effective P-gp blocker with a mechanism different from that of verapamil. Given extremely low toxicity of the compound, aPPD is a potential candidate of chemosensitizer for treatment of multidrug resistant tumors. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PanaGin Pharmaceuticals PanaGin Pharmaceuticals PanaGin Pharmaceuticals
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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".