French Grape Seed OPCs: Cancer-Preventive Compounds

Good Health Lifestyles Research Roundup

You’ve probably heard about grape seed extracts, especially for heart-related conditions. Unfortunately, many grape seed extracts on the market are either adulterated with other ingredients, or are so encumbered with tannins—compounds that limit absorption—that they are virtually useless.

However, grape seed extracts that are free of tannins allow their beneficial components, called oligomeric proanthocyanidins or OPCs, to absorb fully in the digestive tract and ultimately enter into the cells that most need their healing attention. Leading research shows that the right grape seed extract may be the next breakthrough in the fight against cancer.

The studies highlighted here show the value of a French grape seed extract (VX1), standardized for low molecular weight (think “small”) OPCs in stopping colorectal cancer cells from growing and recurring.

According to the Centers for Disease Control and Prevention (CDC), colorectal cancer has the second highest mortality rate in the United States. Fortunately, this latest research provides insight and hope into the newest directions in preventing this cancer and others as well.

 

Stopping Stem-Like Cell “Seeds” with French Grape Seed OPCs

The Study Abstract: Oligomeric proanthocyanidins (OPCs) target cancer stem-like cells and suppress tumor organoid formation in colorectal cancer.

Proanthocyanidins are a heterogeneous group of flavan-3-ol or flavan-3,4-diol oligomers present in various fruits and vegetables. In particular, the smaller oligomeric subset of proanthocyanidins, termed the oligomeric proanthocyanidins (OPCs) appear to have potent anti-tumorigenic properties, but the underlying mechanisms for their effectiveness remain unclear. Herein, we utilized a series of in vitro, in vivo and patient-derived organoid approaches to systematically investigate the chemoprotective role of OPCs in colorectal cancer. OPCs exerted anti-tumorigenic effects through inhibition of cellular proliferation, and induced apoptosis and cell cycle arrest. Intriguingly, OPCs suppressed spheroid derived cancer stem-like cell formation and decreased the expression of intestinal cancer stem cell markers including LGR5, CD44 and CD133. Mechanistically, RNA-sequencing results confirmed that OPCs prominently interfered with developmental and self-renewal pathways and identified several self-renewal associated oncogenes targeted by OPCs. Furthermore, OPCs inhibited Hippo pathway through downregulation of its key transcriptional regulators, YAP and TAZ. Finally, we confirmed anti-tumorigenic effects of OPCs using multiple xenograft experiments and recapitulated its protective effects using patient-derived colorectal tumor organoids. Collectively, we have comprehensively assessed anti-tumorigenic properties of OPCs and our data throws light on previously unrecognized chemopreventive mechanisms of OPCs highlighting its therapeutic potential.

Source: Toden S, Ravindranathan P, Gu J, Cardenas J, Yuchang M, Goel A. Sci Rep. 2018 Feb 20;8(1):3335.

WHAT IT MEANS TO YOU:

Cancer stem cells, the “seeds” of recurring cancer, resist chemotherapy. They essentially hide in the body, remerging later—sometimes years following treatment. When this happens, the new cancer is even more resistant to treatment.

Researchers at Baylor found that French grape seed extract (VX1) stopped the regeneration of cancer stem cells by blocking a specific pathway in the body, abbreviated as Hippo-YAP. In studies, it actually prevented the ability of tumor cells to grow and spread, and eventually killed them altogether. This is an effect not seen with conventional drugs, so these results show the potential for OPCs from grape seed to do something completely unique. In this case, the viability of cancer cells exposed to the extract decreased by 70 percent. Further study using an animal model showed that the VX1 extract suppressed tumor growth by 90 percent. This study shows that the frontiers of natural cancer fighting are still being explored and that the potential for the right kind of grape seed extract—one that is tannin-free and specifically standardized for OPCs—is massive. According to the researchers, a human equivalent dose could be a small addition to a daily regimen—only about 300 mg to 600 mg per day.

 

French Grape Seed OPCs Improve the Effect of Some Chemotherapy Drugs

The Study Abstract: Oligomeric proanthocyanidins (OPCs) from grape seed extract suppress the activity of ABC transporters in overcoming chemoresistance in colorectal cancer cells.

Multidrug resistance is a major hindrance in managing cancer. By performing a series of experiments in chemoresistant colorectal cancer cell lines, we demonstrate that oligomeric proanthocyanidins (OPCs) from grape seed extracts can sensitize both acquired (HCT116-FOr cells) and innately chemoresistant (H716 cells) cancer cells to chemotherapeutic drugs, 5-fluorouracil (5FU) and oxaliplatin, by inhibiting ABC transporter proteins. When combined with chemotherapeutic drugs, OPCs significantly inhibited growth of the chemoresistant cells (p<0.05 to p<0.001), and decreased the expression of several key ABC transporters. Moreover, the activity of the ABC transporters was also significantly decreased by OPCs in the cell lines (p<0.05). We further confirmed that co-treatment with OPCs sensitized the chemoresistant cells to 5FU and oxaliplatin, as observed by improvement in cell cycle arrest, double strand breaks and p53 accumulation in these cells. Additionally, we confirmed that co-administration of OPCs with chemotherapeutic drugs significantly decreased chemoresistant xenograft tumor growth in mice (p<0.05). Together, our study illuminates the downregulation of multiple ABC transporters as a mechanism by which OPCs overcome chemoresistance in cancer cells, and may serve as adjunctive treatments in patients with refractory colorectal cancer.

Source: Ravindranathan P, Pasham D, Goel A. Carcinogenesis. 2018 Dec 29.

WHAT IT MEANS TO YOU:

One of the biggest barriers to conventional cancer treatment is that cancer cells become resistant to chemotherapy drugs. Trying to overcome that with higher dosages isn’t always an option because of the terrible side effects chemotherapy drugs can have on patients. This study found that the oligomeric proanthocyanidins (OPCs) from a French grape seed extract (VX1) inhibited the growth of resistant cancer cells and the proteins that would otherwise help them thrive. This means that the French grape seed OPCs could be part of an adjunct therapy—a beneficial add-on—to chemotherapy in patients with colorectal cancer.

 

For Results, Grape Seed OPCs Are the Critical Factor

The Study Abstract: Mechanistic insights into anticancer properties of oligomeric proanthocyanidins from grape seeds in colorectal cancer.

Although the anticancer properties of oligomeric proanthocyanidins (OPCs) from grape seeds have been well recognized, the molecular mechanisms by which they exert anticancer effects are poorly understood. In this study, through comprehensive RNA-sequencing-based gene expression profiling in multiple colorectal cancer cell lines, we for the first time illuminate the genome-wide effects of OPCs from grape seeds in colorectal cancer. Our data revealed that OPCs affect several key cancer associated genes. In particular, genes involved in cell cycle and DNA replication were most significantly and consistently altered by OPCs across multiple cell lines. Intriguingly, our in vivo experiments showed that OPCs were significantly more potent at decreasing xenograft tumor growth compared with the unfractionated grape seed extract (GSE) that includes the larger polymers of proanthocyanidins. These findings were further confirmed in colorectal cancer patient-derived organoids, wherein OPCs more potently inhibited the formation of organoids compared with GSE. Furthermore, we validated alteration of cell cycle and DNA replication-associated genes in cancer cell lines, mice xenografts as well as patient-derived organoids. Overall, this study provides an unbiased and comprehensive look at the mechanisms by which OPCs exert anticancer properties in colorectal cancer.

Source: Ravindranathan P, Pasham D, Balaji U, Cardenas J, Gu J, Toden S, Goel A. Carcinogenesis. 2018 May 28;39(6):767-777.

WHAT IT MEANS TO YOU:

This study tested grape seed oligomeric proanthocyanidins (OPCs) against a plain, or unfractionated grape seed extract (GSE) that was not tannin-free, nor specifically standardized for the compounds. One of the insights garnered by this research was not just how the OPCs affect cancer-related genes and stop the cell growth cycle, but how much more effective the smaller-sized (low molecular weight) OPCs were in comparison with the larger proanthocyanidins from the regular grape seed extract.

These OPCs target specific microRNAs—in this case the microscopic engineers that replicate cancer cells—and prevent cancer by directly inducing apoptosis (the programmed death of damaged cells). It also boosted levels of tumor suppressor genes, downregulated tumor promoting genes, and prevented the migration of cancer cells.

Although this research focused on colorectal cancer, there are similar types of activity across nearly all kinds of malignancies. In fact, the researchers found that the grape seed worked along so many tracks that in their study they mention, “…no single clinical therapeutic has the ability to effectively block multiple oncogenic pathways…” That alone is an incredible breakthrough.

But in vivo tests found something else even more applicable to everyday life. Because the tannin-free OPCs from French grape seed extract were more absorbable than the tannin-bound OPCs from unfractionated grape seed extract, the botanical ingredient was much more effective at much lower dosages. For example, animal studies found that even at smaller amounts, OPCs were much more effective than standard grape seed extract at reducing tumor size. In just 13 days, 100 mg of OPCs reduced tumor size by 65 percent. Even a 50 mg level brought the tumor size down 40 percent. Compared to standard grape seed extract at only 13 percent and 8 percent, respectively, it shows how much of a difference it makes to get a tannin-free grape seed extract with absorbable OPCs that can reach their full potential. Additionally, there were no harmful effects on healthy cells—these actions were targeted to cancer cells only. Scaled up for human use, researchers determined that low daily dosages—just 240 mg per day—were sufficient.

 

French Grape Seed OPCs Plus Curcumin Are Superior Anti-Carcinogens

The Study Abstract: A combination of curcumin and oligomeric proanthocyanidins offer superior anti-tumorigenic properties in colorectal cancer.

Combining anti-cancer agents in cancer therapies is becoming increasingly popular due to improved efficacy, reduced toxicity and decreased emergence of resistance. Here, we test the hypothesis that dietary agents such as oligomeric proanthocyanidins (OPCs) and curcumin cooperatively modulate cancer-associated cellular mechanisms to inhibit carcinogenesis. By a series of in vitro assays in colorectal cancer cell lines, we showed that the anti-tumorigenic properties of the OPCs-curcumin combination were superior to the effects of individual compounds. By RNA-sequencing based gene expression profiling in six colorectal cancer cell lines, we identified the cooperative modulation of key cancer-associated pathways such as DNA replication and cell cycle pathways. Moreover, several pathways, including protein export, glutathione metabolism and porphyrin metabolism were more effectively modulated by the combination of OPCs and curcumin. We validated genes belonging to these pathways, such as HSPA5, SEC61B, G6PD, HMOX1 and PDE3B to be cooperatively modulated by the OPCs-curcumin combination. We further confirmed that the OPCs-curcumin combination more potently suppresses colorectal carcinogenesis and modulated expression of genes identified by RNA-sequencing in mice xenografts and in colorectal cancer patient-derived organoids. Overall, by delineating the cooperative mechanisms of action of OPCs and curcumin, we make a case for the clinical co-administration of curcumin and OPCs as a treatment therapy for patients with colorectal cancer.

Source: Ravindranathan P, Pasham D, Balaji U, Cardenas J, Gu J, Toden S, Goel A. Sci Rep. 2018 Sep 14;8(1):13869.

WHAT IT MEANS TO YOU:

Tannin-free French grape seed extract with highly absorbable OPCs has already shown strong antitumor effects in prior research. This study combined the OPCs from French grape seed extract with a curcumin from turmeric that is blended with turmeric essential oil and ar-turmerone, a beneficial compound within the oil, for greater absorption.

Both grape seed OPCs and curcumin work along multiple pathways in the body to reduce inflammatory damage to healthy DNA, help prevent cancer cells from replicating, and inhibit the growth and development of tumors. What’s interesting here is that these two botanical ingredients work along differing paths, and because of this, they can cover more ground in the battle against cancer than either one could separately.

As in the other studies, an important key is the form of the ingredients used in the study. The grape seed is tannin-free and specifically standardized for OPCs that can be absorbed in the digestive tract, enter the cells, and start repairing them (or triggering apoptosis, if they’re cancerous.) The curcumin—not to be confused with plain turmeric or standard extracts—uses turmeric essential oil, not piperine, to boost absorption and help it remain in the bloodstream longer.

As the researchers note in their study, it has become increasingly popular to combine cancer-prevention therapies. Both French grape seed OPCs and curcumin represent a one-two punch for reducing cancer risk. The French grape seed is water soluble—it absorbs quickly and works fast. The curcumin is fat soluble and remains in the body longer. This research suggests that this dynamic duo may be an excellent addition to standard therapies.