The overall objective of this work was to increase the knowledge regarding American hybrid grapes and wine-making techniques relevant to the State of Texas, specifically to investigate grape chemistry of hybrid grapes, to evaluate the effects of micro-oxygenation on wine chemistry, and to elucidate anti-cancer effects of wine compounds and extract in colon cancer cells in vitro. The methods used include HPLC-PDA-EIS-MSn and molecular bioassays. The American hybrid grapes, Black Spanish (Vitis aestivalis hybrid) and Blanc Du Bois (Vitis aestivalis hybrid), were compared to Cabernet Sauvignon and Merlot (Vitis vinifera) in their phytochemical composition. Total phenolics were similar in red grape varieties, but lower in white grapes. In Black Spanish grapes, anthocyanins and antioxidant capacity (ORAC) exhibited the highest values. Non-anthocyanin polyphenolics did not show qualitative differences in the four grape varieties. The presence of anthocyanins diglucosides was unique to Black Spanish grapes. The second experiment involved application of micro-oxygenation with oak inner staves to evaluate the effect of this new vinification technology on the stability of anthocyanins. Overall, anthocyanins exhibited significant decreases over time in the following order: control, wine with oak pieces, oak barrel, and micro-oxygenation. The anti-cancer effect of a combination of wine compounds, resveratrol/quercetin (RQ), and a polyphenolic extract from Black Spanish wine were investigated in colon cancer cells HT-29. RQ reduced the generation of reactive oxygen species (ROS), whereas the ORAC increased. RQ reduced cancer cell viability and proliferation, induced caspase-3-cleavage, and increased PARP-cleavage. Additionally, Sp1, Sp3, Sp4, and survivin were down-regulated at mRNA and protein levels. Furthermore, RQ decreased microRNA-27a (miR-27a) and induced ZBTB10, suggesting that RQ interactions with the miR-27a-ZBTB10-axis play a role in Sp down-regulation. Similar results were obtained for the wine extract. This work will provide valuable information regarding grape varieties, potential health benefits of wine, and wine production techniques to the wine industry in Texas and beyond.