Andrographis and curcumin for colon cancer: What the research says

The increase in research validating natural medicines is one of the best developments in recent decades. I have been fortunate to be involved with a number of these studies, with a focus on how botanical compounds can work along a multitude of pathways to stop tumors and the spread of cancer. In one of these recent studies, my colleagues and I examined the ability of a specific andrographis extract (EP80) and a specialized curcumin (BCM-95) to inhibit the growth of colon cancer cells.

Colon cancer is the second leading cause of cancer death in the U.S., making the finding of effective ways of stopping the disease a mission of true urgency.¹ 

Regular colon cancer screening tests, such as colonoscopies, have made finding colon cancer in its initial stages more common, but for 20% of colon cancer patients, their cancer will have already spread by the time it is discovered.^2-4 

Unfortunately, cancer cells quickly develop resistance to conventional chemotherapy drugs. This makes it difficult to find treatments that kill cancer, but not the patient. So finding other safe and effective options is critical. 

Andrographis: A cancer-fighting adaptogen

The herb andrographis (Andrographis paniculata) has been a part of traditional Chinese and Ayurvedic practice for generations. As an adaptogen, it is part of a small group of botanicals that strengthen the ability of the body to adapt to challenges, making it extremely valuable for inhibiting cancer. 

Scientists have linked the andrographis compound andrographolide to stopping the cycle of cancer cell growth, tumor formation and cancer migration in melanoma cells, pancreatic cancer cells and glioblastoma cells. In each study, andrographolide worked along different pathways, showing the versatility of this compound.^5-7 

Additionally, andrographis may one day be used as an adjunct treatment to help overcome chemoresistance. One of the biggest challenges with colon cancer treatment (and most cancers) is many people do not respond well to the standard chemotherapy drug 5-fluorouracil (5-FU). In fact, up to 60% of cancer patients develop chemoresistance. 

Chemotherapy drugs are already toxic to cancer and the patient, so there’s only so far treatment can go before they become too dangerous to pursue further. So when cancer cells are resistant, there appear to be few options. In recent studies, we investigated whether andrographis may help change that. The andrographis we selected is standardized to a minimum of 20% andrographolides — the compounds I mentioned earlier are most associated with the herb’s anti-cancer effects. 

In the experimental models of colorectal cancer using cell samples and xenografted human tumors, the andrographis extract overcame 5-FU resistance, and reduced 5-FU resistant tumor cells. It did this, in part, by inhibiting the DKK1 gene pathway allowing cancer cells to evade natural suppression. We also found andrographis dramatically reduced tumor growth on its own by stopping the mechanisms leading to further cancer cell formation. Combined treatment with both andrographis and 5-FU had a synergistic effect on tumor inhibition, showing the two could be used together for a potentially much higher treatment success rate.⁸ 

Curcumin: A cancer-stopping compound from turmeric

Similarly, curcumin from turmeric (Curcuma longa) has thousands of years of traditional use to back it up and has been extensively studied for its application in fighting cancer. It has been shown to stop cancer initiation, promotion and progression. Published studies on curcumin’s anticancer activity (so far) have found it can suppress breast, prostate, liver, skin, colon, oral and lung tumors.^9-13 

And, as an adjunct to conventional treatment, curcumin can be used as a pretreatment before administering chemotherapy drugs for inhibiting cancer growth. Like andrographis, curcumin increases the activity of cancer drugs and decreases drug resistance in cancer cells. While doing so, it protects normal cells from the toxic effects of those drugs.^12,14 

In one recent study, curcumin enhanced the effectiveness of lenvatinib, a chemotherapy drug commonly prescribed for the treatment of liver cancer. 

Our work showed in tests with lenvatinib-resistant cancer cells, the drug by itself only reduced their number by about 10 to 20%. By comparison, curcumin alone did a better job, reducing them by 25 to 50%. But combining lenvatinib with curcumin was far more effective, reducing cancer cells by almost 75%. And those cancer cells that were completely resistant to lenvatinib, a common occurrence, were reduced by 80% when the drug was combined with curcumin.¹⁵ 

So, there is already robust evidence that, individually, andrographis and curcumin inhibit cancer cell growth, reduce tumor size and enhance the effectiveness of chemotherapy drugs. Because curcumin absorption can be a challenge, we selected a curcumin enhanced with turmeric essential oil for greater bioavailability and practical application in practice. After all, when a nutrient is better absorbed, fewer doses are necessary for positive effects.^8,14-21 

Given the history and known strengths of these botanicals, my colleagues and I wanted to compare the actions of each and then examine their combined efforts on two different colon cancer cell lines. As part of this study, we also conducted sophisticated molecular pathway analyses to chart exactly how andrographis and curcumin exert their anti-cancer effects. 

Andrographis and curcumin combined strongly inhibit colon cancer cells

Our own previous studies showed curcumin and andrographis inhibited proliferation of SW480 and HCT116 colon cancer cell lines most effectively at specific doses: 4 mcg/mL for curcumin and 40 mcg/mL for andrographis. As such, our combined treatment ratio was 1:10 curcumin/andrographis. (For example, the concentration used for SW480 was 2.4 mcg/mL for curcumin and 24.0 mcg/mL for andrographis.) 

As expected, curcumin and andrographis were highly effective at reducing the number of colon cancer cells, with each botanical individually cutting the number of cancer cells by up to 60%. But when combined, the results were even stronger, reducing them by 75%.²² 

Similarly, curcumin and andrographis individually reduced colon cancer proliferation rates by 45 to 75%. Here again, the combination showed the strongest effects, reducing cancer cell invasiveness by 85%.²² 

We also evaluated the effects of the combined treatment on patient-derived 3D organoids. Like the results seen with cancer cells, the combination dramatically suppressed the growth of organoids in both number and size including:  

• The average number of organoids per field dropped from 25.3 to 7.3 in organoid 1 and from 14.7 to 4.7 in organoid 2.  
• The size reduced from 140 micrometers to 117 micrometers for organoid 1 and 158 micrometers to 126 micrometers for organoid 2.²²  

As for the some of the biomechanics behind these results, we found combining these botanicals also made them 10 times more effective at activating the ferroptosis pathway.22 Ferroptosis is a process that kills cancer cells by flooding them with iron, creating intensive oxidative damage and ultimately leads to cancer cell death.²³ 

Additionally, andrographis and curcumin prevented the activity of glutathione peroxidase 4 and ferroptosis suppressor protein 1, two major inhibitors of ferroptosis, that would have otherwise interfered with the cancer-suppressing process.^22,23 

Evidence-based, effective natural medicines deliver hope

When your patients are facing critical health concerns, you can recommend tested, proven and effective natural medicines to help. Whether they are in the midst of treatment, or simply want to prevent the risk of cancer and tumor formation, andrographis and curcumin truly deliver.

AJAY GOEL, PHD, AGAF, is a 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, Calif. He has also been recognized as an American Gastrointestinal Association Fellow (AGAF) for his research on colorectal cancer. Goel has spent more than 20 years researching cancer and has been the lead author of or contributor to more than 300 scientific articles published in peer-reviewed international journals and several book chapters. He is currently researching the prevention of gastrointestinal cancers using integrative and alternative approaches, including botanical products. Botanicals Goel investigates include andrographis, curcumin (from turmeric), boswellia and French grape seed. For inquiries regarding his research, Goel can be reached at ajgoel@coh.org. 

References 

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