Hibiscus-derived gossypin fights melanoma

The end of March and the beginning of April brought the discovery (1) of Texas scientists to light. The researchers tested a little known substance – gossypin – for its action against skin cancer cells. This naturally-occurring flavone was found to inhibit in vitro human melanoma proliferation. Scientists have also observed a unique mechanism that may be responsible for this effect. Furthermore, gossypin therapy, carried out on mice model, reduced the size of melanoma tumors and increased the survival rates. And this is not the only secret property that this flower-derived flavone has.

According to the American Cancer Society (2) melanoma accounts for only approximately 5% of skin cancers, but is responsible for 3 times as many deaths as nonmelanoma skin cancers. What is alarming is that every year the incidence of melanoma increases by 5-7%. Thus in comparison to other malignancies, melanoma incidence is the fastest increasing, right after lung cancer in women. What makes the disease more dreadful is that melanoma is generally the tumor of young patients. For example it is the most common malignant neoplasm in women aged 25-29.

As far as treatment is concerned, surgery is the standard in early stage cutaneous melanoma. A wide local excision with sentinel lymph node biopsy or elective dissection should be performed. Stage IV, or in other words, metastatic melanoma is far more troublesome. Currently it is associated with a 5-year survival rate of around 10%. At present there are no systemic therapeutic regimens that offer significant prolongation of survival without high risk of toxicities. Unfortunately the treatment of patients with advanced-staged melanoma has not improved considerably in recent years.

The need for new approaches to melanoma therapy has led scientist to search for help in natural resources. About 10 years ago it was observed that gossypin exhibits free radical scavenging, antitumor and anticarcinogenic activities (3). The question of how exactly gossypin works has not been answered yet. The following studies (4) have shown that hibiscus-derived flavone inhibits nuclear factor-kappaB (NF-kappaB), which is a transcription factor for genes associated with inflammation, carcinogenesis, hyperproliferation, invasion and angiogenesis. Gossypin hampered NF-kappaB activation induced by inflammatory stimuli and carcinogens, as well as constitutive NF-kappaB in tumor cells.

In the discussed study gossypin was tested on human melanoma cell lines that carry mutations of two kinases. BRAFV600E kinase mutation is said to be present in 70% cases of melanoma in humans. Gossypin inhibited their activities in vitro, possibly through direct binding of flavone with these kinases. This extraordinary activity was confirmed by molecular docking studies. Furthermore, hibiscus-derived compound significantly stunted melanoma growth in a three-dimensional skin culture resembling human skin. Gossypin treatment for 10 days human melanoma cells transplanted to mice reduced tumor volume by inducing the apoptosis.

Other studies show that gossypin may amaze us with its variety of properties. In one protocol it exhibited antidiabetic properties running neck and neck with standard drug gliclazide (5). Other results (6) indicate that gossypin is hypocholesterolemic through the increase in the expression of LDL receptors. Gossypin may also have antiallergic (7) properties as it reduced the histamine release and consequently pruritus in rats. Its anti-inflammatory (8), analgesic (9) and anxiolytic (10) properties could surely find clinical application. Gossypin might also be helpful for patients suffering from Alzheimer’s disease because it reduces the beta-amyloid neurotoxicity (11).

As we see, gossypin is a herbal agent which, surprisingly, seems to be a solution for many ailments of today’s world. On the first look, this flavon may be an extraordinary panaceum, but when we think deeper we might find that most of the plagues of current time result from the inappropriate lifestyle including diet. Scientist try to extract various substances from plants and test them for desirable properties but isn’t it easier to eat lots of fruits and vegetables instead of swallowing pills containing some of their compounds? This is the question that modern society will have to answer one day.

Written by: Natalia Neumann

1.Gossypin as a Novel Selective Dual Inhibitor of v-raf Murine Sarcoma Viral Oncogene Homolog B1 and Cyclin-Dependent Kinase 4 for Melanoma. Shylesh Bhaskaran, Kalarikkal V. Dileep, Sathyaseelan S. Deepa et al. Molecular Cancer Therapeutics April 2013 12:361-372, first published online 29 Mar 2013; DOI: 10.1158/1535-7163.MCT-12-0965;
2.ACS Cancer Facts & Figures 2009http://www.cancer.org/downloads/STT/500809web.pdf
3.J Exp Clin Cancer Res. 2003 Dec;22(4):581-9.Free radical scavenging, antitumor and anticarcinogenic activity of gossypin. Babu BH, Jayram HN, Nair MG et al.
4.Blood. 2007 Jun 15;109(12):5112-21. Epub 2007 Mar 1.Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1-mediated NF-kappaB activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis. Kunnumakkara AB, Nair AS, Ahn KS et al
5.J Diabetes. 2012 Mar;4(1):41-6. doi: 10.1111/j.1753-0407.2011.00145.x. Antidiabetic activity of gossypin, a pentahydroxyflavone glucoside, in streptozotocin-induced experimental diabetes in rats. Venkatesan T, Sorimuthu Pillai S.
6.J Agric Food Chem. 2008 Dec 10;56(23):11526-32. doi: 10.1021/jf802607x. Gossypin up-regulates LDL receptor through activation of ERK pathway: a signaling mechanism for the hypocholesterolemic effect. Lu N, Li Y, Qin H et al.
7.Indian J Biochem Biophys. 2010 Apr;47(2):90-5.Evaluation of anti-allergic activity of gossypin and suramin in mast cell-mediated allergy model.Ganapaty S, Chandrashekhar VM, Narsu ML.
8.Phytother Res. 2009 Jun;23(6):878-84. doi: 10.1002/ptr.2727.Antiinflammatory and antinociceptive activities of gossypin and procumbentin–cyclooxygenase-2 (COX-2) inhibition studies. Mada SR, Metukuri MR, Burugula L et al.
9.Eur J Pharmacol. 1984 Feb 17;98(2):289-91.Gossypin-induced analgesia in mice. Viswanathan S, Sambantham PT, Reddy K et al.
10.Neurochem Res. 2009 Oct;34(10):1867-75. doi: 10.1007/s11064-009-9969-9. Epub 2009 Apr 23. The flavonoid glycosides, myricitrin, gossypin and naringin exert anxiolytic action in mice. Fernandez SP, Nguyen M, Yow TT et al.
11.Arch Pharm Res. 2004 Apr;27(4):454-9.Gossypin protects primary cultured rat cortical cells from oxidative stress- and beta-amyloid-induced toxicity.Yoon I, Lee KH, Cho J.

Would You like to know more? Watch on MEDtube.net: Melanoma in situ

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