When I share that colon cancers - in both men and women - contain estrogen receptors that could be therapeutically targeted, the response is almost always the same: "Really? No one ever told me that."
You're not alone in this surprise. Despite growing research showing that estrogen receptor pathways play crucial roles in colorectal cancer development and progression, this information rarely makes it from research journals into patient education or standard treatment protocols. Yet, understanding these pathways could open doors to powerful integrative support strategies that work in conjunction with conventional care.
With colorectal cancer rates climbing, particularly among younger adults, and affecting over 150,000 Americans annually, we can't afford to overlook well-researched therapeutic possibilities. The science reveals that your colon tissue naturally contains estrogen receptors. As cancer develops, these receptor patterns shift in ways that may influence how your cancer behaves and responds to treatment.
What's particularly exciting is the research on natural compounds, such as silibinin from milk thistle, which acts as a "natural agonist" for the protective estrogen receptor (ERβ), and shikonin, which can selectively target the problematic receptor (ERα). Combined with melatonin's supportive effects, these compounds provide a sophisticated, multi-targeted approach that addresses the complex dynamics of estrogen receptors in colon cancer.
This isn't about replacing your oncology care - it's about understanding additional layers of support that your healthcare team may not be aware of yet. The research is robust, the safety profiles are well-established, and the potential for integration with conventional treatment is promising.
Let's explore what the science tells us about estrogen receptors in colon cancer and how understanding these pathways could inform your healing journey.

The statistics paint a picture that demands immediate attention. Globally, colorectal cancer is the fourth most common cancer. While traditionally affecting older adults, the most alarming trend is among younger people - colorectal cancer has become the leading cause of cancer death in men under 50 in the US, with similar increases worldwide.
What makes this trend particularly concerning is that 75% of young adults diagnosed have no family history of the disease. Traditional risk factors "would only explain a fraction of these cases," suggesting underlying mechanisms—potentially including the estrogen receptor pathways we're about to explore—that haven't been recognised in standard care.
With this representing a younger population group with increasing rates globally, understanding every possible therapeutic avenue becomes urgent.

This might seem surprising, as estrogen is often thought of as a "female hormone," but estrogen receptors are present in the colon tissue of both men and women.
Estrogen Receptor Presence in Colon Cancer

ERβ (Estrogen Receptor Beta) is the predominant estrogen receptor found in both normal and cancerous colon tissue. This receptor is expressed in the colonic epithelium of both sexes, though its expression changes as cancer develops.

ERα (Estrogen Receptor Alpha) is also present but typically at much lower levels in normal colon tissue. However, during cancer development, ERα expression tends to increase.

Estrogen Receptors in Colorectal Cancer: Facts, Novelties and Perspectives - PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC8544350/

Estrogen Receptors and Their Implications in Colorectal Carcinogenesis - PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC4313613/

• ERβ expression decreases in cancerous tissue compared to normal tissue.
• ERα expression increases in malignant cells.
• These changes occur in both men and women with colorectal cancer.r

Profiling estrogen, progesterone, and androgen receptors in colorectal cancer https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1187259/full

• ERβ appears to have protective effects against cancer development and is associated with better outcomes.
• Loss of ERβ expression has been linked to cancer recurrence and worse survival.
• The receptor expression patterns may influence how the cancer behaves and responds to treatment.

One particularly promising finding is silymarin's effect on colorectal cancer stem cells. When administered orally, silibinin significantly reduced cancer stem cell populations and caused tumours to shrink, with decreased growth of new blood vessels. Remarkably, when these affected cancer stem cells were re-injected into new models, they "had lost their potential to repopulate even in the absence of silibinin exposure".
University of Colorado Denver. "Oral milk thistle extract stops colorectal cancer stem cells from growing tumours." ScienceDaily. ScienceDaily, 20 April 2015.
www.sciencedaily.com/releases/2015/04/150420144350.htm

Research indicates that silymarin works synergistically with other compounds, such as curcumin, potentially allowing for lower and safer doses while maintaining effectiveness. The combination approach led to "more cell death by apoptosis than a single compound treatment alone."
https://www.jcancer.org/v07p1250.htm

The research reveals a compelling scientific rationale for combining shikonin, melatonin, and milk thistle in the management of colon cancer, particularly given their complementary effects on estrogen receptor pathways. This combination appears to target both sides of the estrogen receptor equation - inhibiting the problematic ERα while supporting the protective ERβ.

Shikonin's ERα Inhibition
Shikonin demonstrates potent antiestrogen activity by specifically targeting ERα. Research shows it "inhibits tumour cell growth in estrogen receptor alpha (ERalpha)-positive" cancer cells and "decreases its protein level" through proteasome-mediated degradation.
http://pubmed.ncbi.nlm.nih.gov/19760501/

In colon cancer specifically, shikonin "suppressed the growth of colon cancer cells in a dose-dependent manner in vitro and in vivo," while showing "minimal toxicity to non-neoplastic colon cells

Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer -Note: NAC and GSH antioxidants potently rescued shikonin-induced cell death so avoid these anti-oxidants and research indicates that pulsing Piperlingumine will push ROS levels higher, if need be. https://pmc.ncbi.nlm.nih.gov/articles/PMC5752506/

Melatonin provides crucial support by "inhibiting estrogen receptor transactivation" and reducing both ERα expression. In colorectal cancer, where ERβ loss is associated with worse outcomes and cancer progression, melatonin's selective action is particularly beneficial. It can suppress the problematic ERα pathway while leaving the protective ERβ pathway undisturbed.
However, its most significant contribution may be its ability to enhance the effectiveness of other compounds. Studies demonstrate that "melatonin sensitises shikonin-induced cancer cell death" through multiple pathways, including oxidative stress induction and endoplasmic reticulum stress activation.

Melatonin sensitises shikonin-induced cancer cell death mediated by oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7358455/

Biological action of melatonin on target receptors in breast cancer
https://www.scielo.br/j/ramb/a/HVTJc3tXMLQfmw7TcRWXYGJ/

The combination works through multiple complementary pathways:

Oxidative Stress Modulation: Melatonin enhances Shikonin's ability to induce "oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway"
https://pmc.ncbi.nlm.nih.gov/articles/PMC7358455/

Cancer Stem Cell Targeting: Both shikonin and silibinin target cancer stem cells
https://www.sciencedaily.com/releases/2015/04/150420144350.htm
https://pmc.ncbi.nlm.nih.gov/articles/PMC5752506/

ER Stress Induction: The combination promotes endoplasmic reticulum stress, "leading to AKT dephosphorylation"
https://pmc.ncbi.nlm.nih.gov/articles/PMC7358455/

Selective Toxicity: All three compounds show preferential toxicity to cancer cells while protecting normal cells

Clinical case studies demonstrate that melatonin can be safely integrated with conventional chemotherapy, where it "normalised inflammatory markers and alleviated symptoms of polyneuropathy"
https://pubmed.ncbi.nlm.nih.gov/38668052/

This multi-targeted approach represents a sophisticated strategy that addresses the complex estrogen receptor dynamics in colon cancer while supporting overall cellular health. The scientific foundation is robust, though individual responses will vary, and integration with comprehensive cancer care remains essential.

While we've focused on supporting your body's natural estrogen receptor balance, it's crucial to understand that we're living in an environment saturated with hormone-disrupting compounds that may be interfering with these very pathways.

Microplastics, now found in nearly every breath we take, don't just carry chemical additives - the plastic particles themselves can alter sex hormones.
https://www.rutgers.edu/news/plastic-particles-themselves-not-just-chemical-additives-can-alter-sex-hormones

Read my recent post on The Growing Link Between Microplastics and Cancer

Research indicates that polystyrene microplastics can induce estrogenic effects in a dose-dependent manner, increasing estradiol levels and up-regulating both estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) expression. Even more concerning, these particles accumulate in colon tissue and can impact colon cancer cells, potentially increasing metastasis.
https://foodpackagingforum.org/news/study-finds-microplastics-impact-colon-cancer-cells-could-increase-metastasis.

Environmental estrogenic chemicals, including DDT derivatives, PCBs, bisphenol A, and alkylphenols, compete with natural estrogen for binding to both ERα and ERβ.
https://pubmed.ncbi.nlm.nih.gov/9751507/

Mould exposure adds another layer of complexity, as mycotoxins can disrupt hormone balance, further destabilising estrogen receptor function.
https://drtaniadempsey.com/hormones-mold-toxicity/

This everyday toxic burden may partially explain why colorectal cancer rates are rising dramatically in younger adults with no traditional risk factors. When environmental toxins are constantly challenging your estrogen receptor pathways, supporting ERβ function while inhibiting ERα becomes even more critical.

The science is clear: today's colon cancers contain estrogen receptors that influence how the cancer behaves, grows, and responds to treatment. Sadly,  this crucial information rarely reaches patients through conventional channels. Understanding that ERβ protects while ERα promotes cancer progression opens the door to sophisticated, integrative support strategies that can work in conjunction with traditional treatment. Share this information with your standard of care oncologist, as well as your integrative and/or naturopathic practitioners, to raise awareness that could lead to better outcomes for colorectal cancer patients.

The combination of milk thistle's Silibinin (supporting ERβ), Shikonin (inhibiting ERα), and Melatonin (enhancing the effectiveness of both compounds) represents a scientifically grounded approach to optimising your estrogen receptor balance. These aren't experimental compounds - they're well-researched natural medicines with established safety profiles and compelling evidence specifically in colorectal cancer.

In our toxin-laden environment where microplastics, environmental chemicals, and mould exposure constantly challenge our hormone systems, taking proactive steps to support protective pathways becomes even more important. With colorectal cancer rates climbing in people under 50, and traditional risk factors explaining only a fraction of cases, we can't afford to overlook therapeutic avenues that address underlying mechanisms conventional medicine hasn't yet integrated.

This information isn't meant to replace your oncology care - it's meant to enhance it. Your healing journey deserves every evidence-based tool available, especially those that work with your body's natural protective mechanisms rather than against them.

The research exists. The safety data is strong. The mechanistic rationale is compelling. Now may be the perfect time to consider incorporating these strategies into your comprehensive colorectal cancer treatment protocol.

Your healing matters, and this information, which has been hidden in research journals for too long, needs to be considered. Please share this blog article's URL with your community and team rather than copying and pasting any text from within it. Thanks!

© Abbey Mitchell 2025
Admin and founder of The Healing Cancer Study Support Group