Luteolin, Apoptosis, and Cancer: New Research That Can Help Your Dog with Cancer

Luteolin is an important and key ingredient in Dr. Dressler’s nutraceutical, Apocaps. One of the main reasons he included this rather exotic (and hard-to-find) dietary apoptogen is because of its ability to stimulate a process called apoptosis, a necessary process of cell death in the body.

Apoptosis: Natural Cell Suicide

Apoptosis is a means for cells to actually cause themselves to die (a type of cell suicide) to keep growth in check and allow the proper formation of body organs.

For instance, when the future hands of a human embryo are developing, this process of cell death is needed to form the individual fingers. If certain cells in specific locations of the future hand do not die on time and in the proper way, the tissue between the fingers would remain leading to webbed hands instead.

In the case of already formed people and animals, cells that grow too much and do not die when they should is a characteristic of cancer.

(It is well known that the process of apoptosis is hindered in many types of cancer cells. Here is an article discussing why we should target apoptosis, and you can also find more links to abstracts on the reference page about apoptosis.)

Where We Find Luteolin

If you’ve never heard of luteolin, I’m not surprised. It’s not the most common of polyphenols.

Foods rich in luteolin include spicy vegetables like raddichio, bell peppers, chicory, and several chili peppers.

But there are some fruit that pack in luteolin, too, and high up on that list are citrus fruit like lemons, sweet orange, and grapefruit.

It’s also found in that thin red skin you find on peanuts once you crack the shell.

Luteolin is quite bitter, so it’s extracted from the most bitter parts of these foods. A common source for the few supplements that contain luteolin is citrus.

Luteolin and Apoptosis

Numerous published research results are now available showing that luteolin can boost the process of apoptosis. By the time The Dog Cancer Survival Guide was written, most of the scientific research was done in vitro (in test tubes instead of living animals).

Now, there are research results in living animals (in vivo) that support the previous in vitro information.

Luteolin and Colon Cancer

You can read a 2014 published overview (abstract) of an experiment with luteolin done in mice.  It´s pretty technical, but I believe that you can still get the gist of the meaning.

In this experiment, mice with colon cancer were treated with luteolin or not treated. Then, the researchers measured the molecules that are players in the apoptosis process.

They found that these apoptosis-enhancing molecules were greatly increased in the mice that received luteolin.

These results show that luteolin may be a good choice for use as a possible treatment for colon cancer.

Luteolin and Breast Cancer

Another group of scientists looked at the effects of luteolin on mammary (breast) tumors in mice.

The mice were split into two groups: luteolin-treated or -untreated. Then each group was further split into two, and given either high- or low-fat diets. They saw that the mice on high-fat diets in both treated and untreated groups had higher levels of mammary tumor molecules.

But regardless of which diet they received, the mice receiving luteolin treatment were helped.

They had decreased tumor sizes and an increase in the amount of time it took for new tumors to grow.

The researchers concluded that luteolin provided this anti-tumor benefit by enhancing apoptosis.

It’s Not Just Good for Mice

The experiments just mentioned were done in mice, but the same processes occur in dogs, other animals, and people. Most drugs produced by pharmaceutical companies were first done in mice and rats before being tested in people or dogs.

It’s also worth noting that it is generally considered that luteolin is not that well absorbed when given by mouth.

However, luteolin still had beneficial effects in the mentioned studies where it was given to mice by mouth.

Luteolin and Radiation and/or Chemotherapy

What about the effect of luteolin on the usefulness of radiation or chemotherapy (traditional anti-cancer treatments)?

A study published in February 2014 showed that luteolin can increase the ability of a cancer chemotherapy drug to attack tumors.

In this study, researchers transferred human breast cells to living mice. Then they treated one group with chemotherapy alone, and another with chemotherapy and luteolin.

When treated with the drug and luteolin together, the process of apoptosis in the tumors was higher than when the drug was used alone.

Giving luteolin during the drug treatment caused more shrinking of the tumors than giving only the chemotherapy drug.

Luteolin and Chemotherapy-Resistant Tumors

Another group of scientists looked at how luteolin can affect tumor cells (in vitro) that are resistant to a common chemotherapy drug called tamoxifen.

They measured the level of specific molecules present in tumor cells that are resistant to tamoxifen, and saw that luteolin made these tumor cells sensitive to the chemotherapy drug.

These results mean that luteolin can make the drug better able to attack drug-resistant tumors. Therefore, the researchers suggested it be used as a “chemo-sensitizer.”

Luteolin Supports Apoptosis – Safely

All of these findings show the ability of luteolin to enhance apoptosis to help combat tumors. This scientific evidence is important in understanding the benefit of luteolin in dogs being treated for cancer.

It’s also important to note that the scientists of these studies did not report or see any toxic effects due to the luteolin.

So luteolin is safe, as well as supportive.

Luteolin’s Bottom Line

Overall, luteolin has the potential to benefit dogs with cancer because:

1. Luteolin enhances the process of apoptosis that is hindered in cancer cells.
2. Luteolin helps reduce cancer tumor size.
3. Luteolin can delay tumor development.
4. Luteolin can make tumors more sensitive to cancer chemotherapy drugs.

When talking with your veterinarian about using natural products to help your dog that has been diagnosed with cancer, you can share your knowledge of this information to see how it may apply to your dog´s case. Many are excited about the ability to use natural products for illnesses such as cancer. The availability of research helps in the understanding of the benefits of these products.

References and Further Reading

Apoptosis and Dog Cancer

Kasibhatla S, Tseng B. Why target apoptosis in cancer treatment? Mol Cancer Ther. 2003 Jun;2(6):573-80. PMID: 12813137.

Luteolin

Pandurangan AK, Ananda Sadagopan SK, Dharmalingam P, Ganapasam S. Luteolin, a bioflavonoid inhibits Azoxymethane-induced colorectal cancer through activation of Nrf2 signaling. Toxicol Mech Methods. 2014 Jan;24(1):13-20. doi: 10.3109/15376516.2013.843111. Epub 2013 Oct 7. PMID: 24024667.

Song MJ, Lee EJ, Yang Y, Sung MK. Luteolin supplementation modulates mammary tumor growth in C3H mice fed diet with high- and low-fat content. Nutr Cancer. 2014;66(3):523-30. doi: 10.1080/01635581.2013.780629. Epub 2013 Sep 27. PMID: 24074002.

Yang MY, Wang CJ, Chen NF, Ho WH, Lu FJ, Tseng TH. Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDA-MB-231 cells by blocking STAT3. Chem Biol Interact. 2014 Apr 25;213:60-8. doi: 10.1016/j.cbi.2014.02.002. Epub 2014 Feb 11. PMID: 24525192.

Tu SH, Ho CT, Liu MF, Huang CS, Chang HW, Chang CH, Wu CH, Ho YS. Luteolin sensitises drug-resistant human breast cancer cells to tamoxifen via the inhibition of cyclin E2 expression. Food Chem. 2013 Nov 15;141(2):1553-61. doi: 10.1016/j.foodchem.2013.04.077. Epub 2013 May 2. PMID: 23790951.