Diosgenin inhibits growth and induces apoptosis in HCT-116 human colon adenocarcinoma cells by modulating the cholesterol biosynthetic pathway
Bibliographic record
Abstract
3919 Diosgenin, a steroid saponin, is abundantly found in wild yams (Dioscorea villosa Linn) and seeds of fenugreek (Trigonella foenum graecum Linn) and has gained importance as a prospective cancer preventive agent. In this study, we investigated if growth inhibition of HCT-116 human colon adenocarcinoma cells by diosgenin involves the induction of apoptosis. Furthermore, we evaluated if the molecular mechanism of diosgenin involves modulation of key molecules of the cholesterol biosynthetic pathway. Diosgenin treatment resulted in a dose-dependent decrease in the viability and growth of HCT-116 cells. The LD50 of diosgenin in HCT-116 was ∼20 μM after 24 h, and decreased to 7-10 μM after 48 and 72 h treatments. Diosgenin induced apoptosis dose-dependently and involved cleavage of poly (ADP-ribose) polymerase (PARP). The expression of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase was significantly lowered by increasing concentrations of diosgenin. This was accompanied by a dose-dependent decrease in low-density lipoprotein (LDL) receptor. Furthermore, diosgenin treatment resulted in a significant, dose-dependent decrease in the expressions of β-catenin, peroxisome proliferator-activated receptor (PPAR) -γ, insulin-like growth factor (IGF)-1 and IGF-1 receptor in HCT-116 cells. Our data suggests that diosgenin is a potent inhibitor of HCT-116 colon adenocarcinoma cells by inducing apoptosis and inhibiting multiple molecular targets including the cholesterol biosynthetic pathway, and the Wnt and IGF-1-mediated pathways. In conclusion, our results indicate the molecular mode of action of diosgenin and its potential use as a chemopreventive agent against colon cancer.
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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) | 0.000 | 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".