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Abstract Ginsenosides, the bioactive components of ginseng, can be divided into two major groups, namely 20(S)-protopanaxatriol (e.g. Re, Rg1, Rg2, and Rb3) and 20(S)-protopanaxadiol (e.g. Rb1, Rb2, Rc, and Rd). Biological and environmental factors may affect the content of ginsenosides in different parts of ginseng plant. Evidence from pharmacokinetic and metabolic studies of Re demonstrated that (1) the absorption of Re is fast in gastrointestinal tract; (2) Re may be metabolized mainly to Rh1 and F1 by intestinal microflora before absorption into blood; and (3) Re is quickly cleared from the body.

Background: Vitamin D was first hypothesized to play a role in cancer chemoprevention in 1980 when it was observed that there was a higher rate of colon cancer in the Northern USA as compared with populations living in the South. While cholecalciferol (vitamin D3) has been tested in many cancer-cell lines, published results for ergocalciferol (vitamin D2) are lacking for most epithelial cell cancers, and combination studies of both D2 and D3 and vitamin A (retinoic acid) are lacking in general. The goal of the study was to investigate the effects of vitamins D2, D3, and A, alone and in combination on the growth of all gastric and colon cancer cell lines in vitro. Methods: Colon (SW480 and HCT-116) and gastric (AGS and NCI-N87) cell lines were treated with varying concentrations of D2, D3 and all-trans retinoic acid (ATRA) and combinations thereof. Cell viability and cytotoxicity were measured using the CellTiter-Glo® 2.0 assay, while caspase activities and cytotoxicity were determined using the Caspase-Glo® 3/7, Caspase 8, ApoTox-Glo™ Triplex assays. Autophagy was determined using the CYTO-ID® Autophagy Detection Kit 2.0. Gene expression studies were performed using qPCR. Results: Both vitamin D2 and D3 inhibited the growth of all cell lines tested, with IC50 ranging from 19-56 µM. However, when combined (1:1), the IC50 for the combination of D2 and D3 was significantly reduced to a range of 5-6.0 µM indicating synergism. ATRA also inhibited the growth of all cell lines tested with an IC50 range of 2.6 to 5.6 µM. When ATRA was combined with D2 and D3, the IC50s were significantly reduced to 0.65 to 1.4 µM, further indicating synergistic effects. In the gastric and colon cancer cell lines, the combination induced apoptosis via caspase 3/7 and 8, increased the Bax/Bcl-2 ratio, while in the SW480 colon cancer line, the combination also induced autophagy. Conclusion: Our data demonstrated that vitamins D2, D3 and ATRA inhibit the proliferation of colon and gastric cancer cells. The combinations of D2+D3 or ATRA+D2+D3 had synergistic effects or additive effects on all cell lines tested, increased Bax expression and the Bax/Bcl-2 ratio, and increased caspase 3/7 and 8 activities to favor apoptosis. In SW480 colon cancer cells the combination also induced autophagy. This data suggest that combinations of vitamins A and D have synergistic effects in colon and gastric cancers, and considering the potential clinical implications, further research is justified. [ABSTRACT FROM AUTHOR]

Ginsenosides, the bioactive components of ginseng, can be divided into two major groups, namely 20(S)- protopanaxatriol (e.g. Re, Rg1, Rg2, and Rb3) and 20(S)-protopanaxadiol (e.g. Rb1, Rb2, Rc, and Rd). Biological and environmental factors may affect the content of ginsenosides in different parts of ginseng plant. Evidence from pharmacokinetic and metabolic studies of Re demonstrated that (1) the absorption of Re is fast in gastrointestinal tract; (2) Re may be metabolized mainly to Rh1 and F1 by intestinal microflora before absorption into blood; and (3) Re is quickly cleared from the body. [ABSTRACT FROM AUTHOR]