Multidrug resistance continues to pose significant challenges in cancer management, making it much harder for patients to experience positive outcomes.
Using higher dosages of the chemotherapy drugs is not a viable solution because patients typically cannot tolerate the debilitating side effects. In a game-changing study, scientists uncovered a solution that overcomes chemoresistance without increasing damaging side effects.
The study results were published earlier this year in Carcinogenesis.
Researchers, which included Ajay Goel, Ph.D, AGAF, Professor and Chair, Department of Translational Genomics and Oncology at the Beckman Research Institute City of Hope Comprehensive Cancer Center, as well as Director of Biotech Innovations at the City of Hope Medical Center, in Duarte, California, conducted a series of experiments using chemoresistant colorectal cancer cell lines. The results clearly demonstrated that oligomeric proanythocyanidins (OPCs) from French grape seed extract boosted the effectiveness of two chemotherapy drugs, 5FU and oxaliplatin.
The study showed that the OPCs in French Grape Seed VX1 helped overcome the problem of chemoresistance by inhibiting specific proteins called ABC (adenosine triphosphate-binding cassette) transporters. ABC transporters “teach” cancer cells how to resist chemotherapy drugs. The OPCs in French Grape Seed VX1 decreased the expression of several ABC transporters and reduced their activity inside the colorectal cancer cells.
The OPCs in French Grape Seed VX1 also increased the drugs’ cancer cell “kill rate” by up to 90%. The OPCs in French Grape Seed VX1 sensitized the colorectal cancer cells to 5FU and oxaliplatin, allowing the drugs to do their jobs more effectively. The researchers observed significant improvement in the ways the cancer cells responded to the combined treatment.
From there, the researchers moved to an animal model of chemoresistant colorectal cancer. Tumors growth continued when the mice were treated with 5FU or oxaliplatin alone. When the researchers added the OPCs in French Grape Seed VX1 to the drugs, tumor growth decreased significantly.
By reducing the presence and activity of ABC transporters, the OPCs in French Grape Seed VX1 significantly increased the effectiveness of chemotherapy drugs in both in vitro and in vivo models of chemoresistant colorectal cancer.
The OPCs in French Grape Seed VX1 could be used as an adjunct therapy to standard chemotherapy for patients with colorectal cancer.
Ravindranathan P, Pasham D, Goel A. Oligomeric proanthocyanidins (OPCs) from grape seed extract suppress the activity of ABC transporters in overcoming chemoresistance in colorectal cancer cells. Carcinogenesis. 2019 May 14;40(3):412-421. doi: 10.1093/carcin/bgy184.[Pubmed][Article]