Hot News: Curry, Curcumin, Cancer & Cure

*Hot* News via Twitter and various news media a few days ago. Big headlines tell the following in respectively The Sun, Herald, Ireland, BBC News / NHS Health and Reuters:

Curry is a ‘cure for cancer‘

Spices in curry may help cure cancer

Curry spice ‘kills cancer cells‘

Scientists say curry compound kills cancer cells

The message of these headlines is quite different and so are the articles themselves (covered more in depth by @jdc325 at the BadScience Blog “Stuff and Nonsense” (see here)). They vary from “curry being a cure for cancer” to “a possible effect of one of its compounds on cancer cells”.

So what was (not) done?

1. Cancer was not cured.
2. It was not a human trial.
3. The study didn’t test effects on living laboratory animals, like mice, either.
4. The study was done in the test tube, using individual cancer cell lines.
5. The cells tested were (only) esophageal cancer cell lines.
6. Testing the drugs efficacy was not the main aim of the study.
7. Curry (a complex spicy mixture) wasn’t used.
8. Curcumin was tested, which makes up 3% of “turmeric”, that is one of the spices in curry.
9. That curcumin has some anti-carcinogenic effects is not new (see my tweet linking to 1120 hits in PubMed with a  simple PubMed search for curcumin and cancer: http://bit.ly/3Qydc6)

So why the fuss? This doesn’t seem to be a terribly shocking study. Why the media picked this one up is unclear. It must have been, because they were sleeping (missed all the previous studies on curcumin) and/or because they are fond of these kind of studies: except from the experimental details- these studies translate so well to the general public: food – cure – cancer.

And the headlines do it much better than the actual title of the article:

Curcumin induces apoptosis-independent death in oesophageal cancer cells

I experienced the same when my study was picked up at a cancer conference by BBC-health, whereas other far more pioneering studies were not: these were harder to grasp and to explain ‘to the public’ and without any possible direct health benefit.

What was already known about curcumin and cancer? What was done in the present study? What is new? And is curcumin really a promising agent?

Already known.

Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. It gives the curry it bright yellow color. Curcumin has a plethora of beneficial effects in vitro (in the test tube) and in animal studies, including anti-microbial,  anti-arthritic and  anti-inflammatory effects, but most interesting is its anti-carcinogenic effect. It has potential for both prevention and therapy of cancer, but the evidence for preventive effects is most convincing. The mechanisms playing a role in the anticarcinogenic effect are also multifold and complex. Possible mechanisms include: Inhibition/protection from DNA damage/alterations, Inhibition of angiogenesis, Inhibition of invasion/metastasis, Induction of apoptosis, Antioxidant activity, Induction of GST, Inhibition of cytochromes P450, I NF-jB, AP-1, MMPs, COX-2, TNF-a, IL-6, iNOS, IL-1b, the oncogens ras/fos/jun/myc, MAPK, ornithine decarboxylase, Activation of Nrf2, Induction of HO-1, Activation of PPAR-c  and Immunostimulant/immunorestorer effect……….[2]

New Findings

This is to put in perspective that the researchers found yet another possible mechanism (although others have found evidence before, see introduction [1]). Using a small panel of esophagus cancer cells, they first showed that the cells were selectively killed by curcumin. Next they showed that the major mechanism wasn’t apoptosis, cell death by suicide, but cell death by a mechanism called “Mitotic catastrophe”, a type of cell death that occurs during mitosis (cell division) (see free review in Oncogene [3]). As with apoptosis many steps have to go wrong before the cell will undergo mitotic catastrophe. The researchers show that curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin–proteasome system: ubiquitin labels proteins for degradation by proteasomes, thereby controlling the stability, function, and intracellular localization of a wide variety of proteins.

In other words, this study is mainly about the mechanisms behind the anti-cancer effects of curcumin.

Cure?

Of course this paper itself has no direct relevance to the management of human esophagus cancer. The sentence that may have triggered the media is:

“Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of esophageal cancer.”

Which is of course to far-fetched. The authors refer to the fact that esophageal cancers are often resistant to cell death induction with chemotherapeutic drugs, but this only indirectly points at a possible role for curcumin.

It has to be stressed that no human study has convincingly shown an anti-tumor effects of curcumin. Studies that have been done are observational, i.e. show that people taking higher concentrations of curcumin in their diet have a lower incidence of several common cancer types. However, such studies are prone to bias: several other factors (alone or in together) can be responsible for a anti-cancer effect (see previous post [5] explaining this for other nutrients).

The Current grade of evidence for a preventive or therapeutic effect is C, which means “unclear scientific evidence” (see MedlinePlus).

Although there are several trials under way there is reason to be skeptical about the potential of curcumin as cancertherapeutic agent.

• The limited bioavailability and extensive metabolism of curcumin suggest that many of its anticancer effects observed in vitro may not be attainable in vivo. On the other the gastro-intestinal system is he most likely place for an effect of curcimin taken by the oral route. [2]
• Although relatively high concentrations of curcumin have not shown significant toxicity in short-term studies, these concentrations may lead to toxic and carcinogenic effects in the long term.[2]
• The therapeutic effects are dose-dependent. As often seen with these bioactive compounds, toxic effects can occur at supra-optimal amounts. Indeed curcumin has shown to be toxic and carcinogenic under specific conditions. At low and high doses curcumin behaves as an anti-oxidant and a pro-oxidant (toxic) respectively. [2, 6 ]
• Often more ingredients add to the therapeutic effect, or more foods/habits [5].
• The FDA has a shortlist of “187 Fake Cancer “Cures” Consumers Should Avoid”, compounds containing curcumin are on that list [7].

Conclusion

So, concluding, a study that unraveled one of the mechanisms whereby curcumin can kill cancer cells, led to an exaggerated and sometimes completely wrong coverage in the media. Why this was done is unclear, but the ultimate result of such misplaced drumroll will only lead to disbelief or carelessness.

Shame on you, media!!

Photo credits

http://www.flickr.com/photos/trentstrohm/347513745/

References

1. O’Sullivan-Coyne, G., O’Sullivan, G., O’Donovan, T., Piwocka, K., & McKenna, S. (2009). Curcumin induces apoptosis-independent death in oesophageal cancer cells British Journal of Cancer, 101 (9), 1585-1595 DOI: 10.1038/sj.bjc.6605308
2. López-Lázaro, M. (2008). Anticancer and carcinogenic properties of curcumin: Considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent Molecular Nutrition & Food Research DOI: 10.1002/mnfr.200700238
3. Castedo, M., Perfettini, J., Roumier, T., Andreau, K., Medema, R., & Kroemer, G. (2004). Cell death by mitotic catastrophe: a molecular definition Oncogene, 23 (16), 2825-2837 DOI: 10.1038/sj.onc.1207528
4. Stuff and Nonsense – Curry can cure cancer, say scientists (2009/10/28)
5. The best study design for dummies (2008/08/25)
6. Huge disappointment: Selenium and Vitamin E fail to Prevent Prostate Cancer.(post on this blog about the SELECT trial – 2008/11/16)
7. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/ucm171057.htm

You may also want to read:

• MnSOD, Carotenoids & Prostate Cancer – “You are what you eat” depends on who you are. (2009/02/22/
• Yet another negative trial with vitamins in prostate cancer vitamins c and e (2008/12/15)

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