Abstract 1269: Diosgenin, a naturally occurring steroidal saponin, prevents colon cancer in animal models of hereditary and sporadic CRC
Notice bibliographique
Résumé
Abstract Colorectal Cancer (CRC) affects more than 1.35 million people worldwide annually. In the US it is anticipated ~140,000 new cases and 50,000 deaths for the year 2017. In spite of existing preventive measures, recent data suggest an increase in the number of CRC incidences in the younger age groups (30 to 55 years) urging the need for better preventives. In the present study we have studied, Diosgenin against colon cancer in APCmin/+ mice and azoxymethane (AOM)-induced rat CRC models. Diosgenin is a steroid saponin with proven diverse medicinal properties, including anti-diabetic, antiobesity and antiinflammatory, and anticancer properties. APCmin/+ mice, a hereditary polyposis mouse model, were bred in-house and starting at 6 weeks age they were given AIN7-6A diets containing diosgenin (0, 500 and 1,000 ppm) for 14 weeks. At 20-wks of age all mice were euthanized and intestines, both small and large, were analyzed for tumors. In the sporadic CRC model, colon tumors were induced in the male F344 rats by two weekly s.c. injections of AOM (15mg/kg BW) followed by diosgenin administration (0 and 1,000ppm) for 38 weeks. Dietary diosgenin showed significant suppression of colon tumor incidence and multiplicity in both models. In APCmin/+ mice both small intestinal polyps (SIP) and colon tumors (CT) were suppressed in a dose-dependent manner with a significant effect in the high-dose treatment. Diosgenin administered female mice had 33% (25±4.1; Mean±SE, p<0.044) and 54% (17.1+3.8; p<0.003) inhibition of SIP as compared to control mice (37.3±5.6); in male mice there was a greater inhibitory effect (p<0.0001) with 53% (14.1±1.8;) and 65% (10.7±1.7; p<0.0001) suppression of the SIP at 500 and 1,000 ppm respectively, as compared to control mice (30.4±2.3). Colon tumor multiplicity was also inhibited by 65% (0.45±0.24; p<0.05) and 50% (0.5±0.18; p>0.05) with high dose in both male and female mice as compared to their respective controls (1.3±0.20 and 1.0±0.25). Importantly, diosgenin showed a similar inhibitory effect on AOM-induced colon adenocarcinoma incidence and multiplicity in the rat model. Administration of diosgenin significantly suppressed both invasive and non-invasive colon adenocarcinoma incidence by 60% (p<0.005) and multiplicity by 65 % (p<0.0001). HPLC analysis of the intestinal contents of diosgenin suggested that more than 50% reached the colon in its active form. Biomarker analysis suggested that the strong chemopreventive effects are due to the suppression of proliferation (PCNA) and pro-inflammatory proteins (COX-2 and iNOS) with an increase in apoptosis (Casp-3). Based on these results from the preclinical models representing both hereditary and sporadic CRC patients, it is highly imperative to conclude that diosgenin is a potential chemopreventive agent for colon cancer prevention which needs to be further investigated in the clinic. (Endowed Chair Funds from CVR/ASA) Citation Format: Venkateshwar Madka, Jayadev Raju, Gopal Pathuri, Snigdha Smriti, Anh Bao, Yuting Zhang, Nicole Stratton, Mudassir Farooqui, Stanley Lightfoot, Adam S. Asch, Chinthalapally V. Rao. Diosgenin, a naturally occurring steroidal saponin, prevents colon cancer in animal models of hereditary and sporadic CRC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1269.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».