Soursop: Cancer killing fruit

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Hello welcome reader,

This post is based on soursop and the claimed cancer killing capacities that this fruit possesses. The context to this post is result of a social media post I recently saw shared by a friend, a post you have most likely seen yourself (figure 1).

Figure 1. Example of part of social media post on soursop.

This post states (not suggests) that soursop is a 'cancer killer 10,000 times stronger that chemo.' I have never heard of soursop until 2 weeks ago, and so all these questions began eating at my mind, what is soursop? How does it kill cancer? Is it more effective than chemo-therapy? Is this too good to be true? If it is true then why the hell have I not heard of it? I must admit, the fact that the very first sentence reads 'share this information first and read afterwards' is less than encouraging, I entered this research expecting to find a run of the mill hoax attempting to take advantage of people at their most vulnerable. I was to find studies confirming this post sooner than those refuting it...

What is soursop?

Soursop is known by many names, (wikipedia has a nice list, but they are irrelevant to this post) soursop and graviola are the most common. Soursop is the fruit of the Annona muricata, a tree member to the Annonaceae family. Ingredients within Soursop have been recognised as variously cytotoxic, pesticidal, antimalarial, antiparasitic, antimicrobial, and anti-tumoral [7]. The fruit can be seen in figure 2.

What is cancer?

There are more than 200 different types of cancer, each with individual treatments, symptoms and causes (for more statistics and facts on cancer visit cancer research UK [1]). Due to the increased attention towards early detection and  prevention of cancer a number of cancer type (stomach, colon, breast) cases have fallen dramatically over the last 18 years. However cancers such as pancreatic, ovary, and leukemia have remained [2]. In normal cell activity, millions and millions of cells in your body are produced, serve their function, die, and are replaced. Damage to cell DNA (through any number of causes) can result in mutation causing the cell to uncontrollably divide and not under go apoptosis (programmed cell death), creating a cancerous tumor. Due to this rapid cellular division greater energy (or ATP) is required, for example breast cancer cells can metabolize 17 times more glucose than a non-cancerous cell [3,4]. This is significant as it creates a distinguishing characterstic between cancerous and non-cancerous cell, the cancerous cell is dependent on more ATP. Some cancerous cells develop a resistance to common chemo-therapy agents (adriamycin, vincristine, and taxol) as well as multitude of other anti-cancerous agents (these cells resistant to multiple drugs are termed multi-drug resistant cells; or MDR cells). This resistance is attributed to additional intra-cellular 'pumps' that remove the anti-cancerous agents before they can accumulate to lethal doses [6].

How it Works

The active ingredients in soursop is a phytochemical called Annonaceous acetogenins  (ACG's). Chemically, ACG's are derivatives of long-chain fatty acids. Biologically, they express potent bioactivities through the depletion of ATP levels via inhibiting the complex 1 of mitochondria and        Figure 2: Soursop (Graviola)

inhibiting NADH oxidase of plasma membrane of tumor cells [5], it sounds complex, essentially ACG's starve the tumor cells of ATP, resulting in apoptosis. ACG's have been shown to thwart MDR cancerous cells at an equal or lower dose of that required for typical cancerous cells [2]. This could be a result of the additional ATP required for the 'pumps' clearing the MDR cells of anti-cancerous agents. Highlighting a correlation between the toxicity of ACG's and cells ATP requirement. The spectacular thing is that given the correct dosage ACG's have been observed to discriminate between cancerous and non-cancerous cells [2,5,6,7,8]. Meaning healthy cells are not effected. This is currently attributed to oxidase activity (inhibited by ACG's) being over-expressed in cancerous cell lining [7]. For example, a highly relevant study [8] isolated five compounds from within the soursop seed observing that one (cis-annonacin-10-one) was selectively toxic to colon cancerous cells in which the compound was 10,000 times more effective than adriamycin (chemo-therapy agent). And so the post (figure 1) does holds some truth, the exaggeration of this isolated compound having an effect on one type of cancer cell when compared to only one chemotherapy agent is however unwarranted and potentially dangerous particularly when further research unearths concerning facts about ACG's. But questions are raised , why are we not aware of this product? And who is conducting large scale human testing? 

Controversy

The post (figure 1) states that this product and knowledge is being withheld from us because 'some big corporation want to make back their money spent on years of research by trying to make a synthetic version of it for sale.' In argument to this it must be acknowledged that many of our drugs and health supplements are derivative of a natural source, nevertheless millions of pounds are made everyday. One post made an aggressive but relevant comment saying that pharmaceuticals refuse to cure cancer because they will lose a huge commodity. However, Soursop products are available for purchase, 120 Graviola vegicaps containing fruit and seed powder can be purchased  for £19.99 [9]. Furthermore, Tesco's sell Guanabana (soursop) juice, 1L for £1.49 [10]. And so soursop is not being kept from the market at all. Even so this area is currently lacking studies employing large human samples to confirm the cancer killing effects of the ACG's in soursop fruit. 

And I think I know why...

The Wolf in sheep's clothing 

Soursop contains neurodegenerative toxins. Alkaloids within soursop are toxic to mesencephalic dopaminergic neurons (literally meaning ‘mid-brain dopamine-related neurons’) and thus could contribute to neurodegenerative processes [11,14]. In addition to these alkaloids the Annonaceae family contain potent  mitochondrial complex 1 inhibitors extremely toxic to dopaminergic and other mesencephalic (mid-brain) neurons, I am of course referring to ACG's. Specifically annonacin (accounting for ~70% of all ACG's in soursop extract [12]). As previously mentioned these ACG's (and therefore) annonacin are fatty-acid derivatives, as a result of this lipophilic profile annonacin can pass through cell membranes spreading through the brain causing neuron death not limited to dopaminergic neurons [11]. The damage that this neuronal death can cause may have already been researched, it is a well studied phenomenon that Guadeloupe has extraordinarily inflated numbers of atypical Parkinson's disease. These atypical cases represent two-thirds of all Parkinsonism cases on this island, compared to the 5% reported in European countries [13]. A study included 265 Parkinsonism patients referred to a hospital in Guadeloupe identifying that 100 of these patients displayed unclassifiable Parkinsonism, this same study deduced that the regular consumption of Annonaceae fruits containing neurotoxins (alkaloids and ACG's) which induce dopaminergic neuron loss in animals could be a probable cause [15]. Further supporting evidence can be found in Lannuzel et al. [16] where 70% of Parkinson's disease patients displayed atypical forms of levodopa (main drug used to treat parkinsonism) unresponsive Parkinsonism. A comparison of the 30% (typical) to the 70% (atypical) revealed that the latter consumed significantly more fruit, infusions or decoction of leaves from plants of the annonaceae familiy, specifically Annona muricata (soursop). Figure 3 demonstrate the catastrophic effects annanocin can have on the striatum (part of the fore brain) in rats

Figure 3. Histological alterations visualized by Bodian silver impregnation in the striatum of annonacin-treated rats. Enlarged, dystrophic nuclie can be observed in the annonacin-treated but not in the control case [16].

In 2008 epidemiological data suggested a close association between atypical Parkinsonism and regular consumption of soursop, identifying annanocin as a probable etiological factor. Consistent with this view annanocin-treated rats (similar to that in [16] and figure 3) reproduced brain lesions representative of the human disease [13,17]. This certainly does spell concern for the soursop product such as Tesco's guanabana 1L and the Graviola vegicaps recommending consumption of 3-6 capsules per day [9,10]. To put this in perspective a study quantified the amount of annanocin within an average soursop (15mg) and a can of soursop nectar (36mg), clarifying the toxicity by stating the ingestion of one soursop a day for a year would by estimates accumulate the same relative volume of annanocin that caused brain lesions in rats [12]. What about one a week? Or one a month? Continuous low doses of annanocin have been shown to irreversibly commit neurons to death [11]. However this statement is derived from a non-human based study where annanocin treatment lasted 24-hours. Therefore further study is required before any kind of supported recommendation can be made. I shall close this section with the closing statements of a study [16]; the consumption of annonaceae in Guadeloupe and other tropical areas constitutes a serious public health problem, further investigation is therefore urgently needed.

Conclusions

It is clear that more testing needs to be completed before an absolute truth can be attained concerning soursop and its potential benefits. It also becomes clear why large scale human studies are non-existent, until the toxins can be dealt with scientists and pharmaceuticals alike will refrain administering a substance to subjects in studies that is so closely associated with atypical Parkinsonism. From a health perspective I will and recommend you stay well away, at least until the neurotixic agents are better understood or even manageable. Regarding the cancer killing capacity of this fruit, it is most definitely promising and future research may hold prospects of an ACG based cure/preventative but right now, it comes at too steep a price.  As a cancer cure? If the unspeakable diagnosis is in my fate I know what I would do. But that is irrelevant, with the evidence before you what do you think?

Your very own health nut,

Chris

Main sources:

[1] http://www.cancerresearchuk.org/cancer-info/cancerstats/keyfacts/Allcancerscombined/?script=true

[2] McLaughlin, J.L. (2008) Paw Paw and Cancer: Annonaceous Acetogenins from Discovery to Commercial Products. Journal of Natural Products, 71(7): pp1311-1320. 

[3] Papa, V., Pezzino, V., Constantino, A., Belfiore, A., Giuffrida, D., Frittitta, L. Vannelli, G.B., Brand, R., Goldfine, I.D. & Vigneri, R. (1990) Elevated insulin receptor content in human breast cancer. The Journal of Clinical Investigation, 86(5): pp1503-1510.

[4] Cullen, K.J., Yee, D., Sly, W.S., Perdue, J., Hampton, B., Lippman, M.F. & Rosen, N. (1990) Insulin-like growth factor receptor expression and function in human breast cancer. Cancer Research, 50(1): pp48-53.

[5] Alali, F.Q., Liu, X.X. & McLaughlin, J.L. (1999) Annonaceous acetogenins: recent progress. Journal of Natural Products, 62(3): pp504-540.

[6] Oberlies, N.H., Jones, J.L., Corbett, T.H., Fotopoulos, S.S. & McLaughlin, J.L. (1995) Tumor cell growth by several Annonaceous acetogenins in an in vitro diffusion assay. Cancer Letters, 96(1): pp55-62.

[7] Morre, D.J., Cabo, R.D., Farley, C., Oberlies, N.H. & McLaughlin, J.L. (1995) Mode of action of bullatacin, a potent antitumor acetogenin: inhibition of NADH oxidase activity of HELA and HL-60, but not liver, plasma membranes. Life Sciences, 56(5): pp343-348.

[8] Rieser, M.J., Gu, Z.M., Fang, X.P., Zeng, L., Wood, K.V. & McLaughlin, J.L. (1996) Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata. Journal of Natural Products, 59(2): pp100-108.

[9] https://www.thefinchleyclinic.com/shop/graviola-120-vegicaps-p-710.html?gclid=CjwKEAjwgYKfBRDvgJeylem9xDUSJACjeQ7A0d82kPuBeD4uC4fv30U0YvpcYHcxtRMQojXrtNQ68xoCNrbw_wcB&utm_campaign=google_merchant&utm_medium=product_search&utm_source=google_merchant&osCsid=d35ba03be3357a95e3cc7f4f1d9f232f

[10] http://www.tesco.com/groceries/Product/Details/?id=256735746

[11] Lannuzel, A., Michel, P.P., Hoglinger, G.U, Champy, P., Jousset, A., Medja, F., Lombes, A., Darios, F., Gleye, C., Laurens,  A., Hocquemiller, R., Hirsch, E.C. & Ruberg, M. (2003) The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism. Neuroscience, 121(2): pp287-296.

[12] Champy, P., Melot, A., Guerineau Eng, V., Gleye, C., Fall, D., Hoglinger, G.U., Ruberg, M., Lannuzel, A., Laprevote, O., Laurens, A. & Hocquemiller, R. (2005) Quantification of Acetogenins in
Annona muricata Linked to Atypical Parkinsonism in Guadeloupe. Movement Disorders, 20(12): pp1629-1633.

[13] Lannuzel, A., Ruberg, M. & Michel, P.P. (2008) Atypical parkinsonism in the Caribbean island of Guadeloupe: etiological role of the mitochondrial complex I inhibitor annonacin. Movement Disorders, 23(15): pp2122-2128.

[14] http://www.mskcc.org/cancer-care/herb/graviola

[15] Caparrao-Lefebvre, D. & Lees, A.J. (2005) Atypical unclassifiable parkinsonism on Guadeloupe: an environmental toxic hypothesis. Movement Disorders, Suppl 12:S114-118.

[16] Lannuzel, A., Hoglinger, G.U., Champy, P., Michel, P.P., Hirsch, E.C. & Ruberg, M. (2006) Is atypical parkinsonism in the Caribbean caused by the consumption of Annonacae? Journal of Neural Transmission. Supplementum, Suppl (70): pp153-157.

[17] Champy, P., Hoglinger, G.U., Feger, J., Gleye, C., Hocquemiller, R., Laurens, A., Guerineau, V., Laprevote, O., Medja, F., Lombes, A., Michel, P.P., Lannuzel, A., Hirsch, E.C. & Ruberg, M. (2004) Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe. Journal of Neurochemistry, 88(1): pp63-69.