Insects employed to treat cancer, HIV

Besides the traditional use of insects such as termites and grasshoppers as part of the Nigerian diet for their nutritive values, scientists have bioengineered these local delicacies in the treatment of cancer, diabetes, rheumatoid arthritis, Human Immuno-deficiency Virus (HIV), wounds among other benefits. CHUKWUMA MUANYA writes.

A study published in the Journal of Agriculture and Food Chemistry found that insects could provide as much magnesium, iron, and other nutrients as steak.

And researchers at the American Chemical Society (ACS) found grasshoppers and crickets to be a far better source of many nutrients, particularly iron, compared to beef.

Grasshoppers, mealworms, termites and crickets all had higher concentrations of chemically available calcium, copper and zinc than the sirloin.

In Nigeria, termites are usually roasted and eaten as food, mostly during the rainy season.

Besides the use of termites as therapeutic resource for the treatment of asthma, hoarseness and sinusitis, wounds, malnutrition, nutrient deficiency and sickness of pregnant women, researchers have explored the use of insect natural products as potential source for alternative medicines.

Indian researchers from Department of Biological Sciences, Presidency University, Kolkata; Department of Zoology, Darjeeling Government College, West Bengal; and Department of Zoology, Scottish Church College, Kolkata explored developments in bioengineering natural products from insects with potential use in modern medicines as well as in utilisation of insects as models for studying essential mammalian processes such as immune responses to pathogens.

The study was published in World Science News.

The researchers listed natural products derived from insects possess medicinal value:

Honey bee products used as medicine
Bee products such as honey, venom have been used in folk medicine for thousands of years for treating wounds, ulcers, inflammation, infections, pain, allergies and cancer.

Bee venom therapy, the therapeutic application of bee venom have been used in traditional medicine to treat diseases, such as arthritis, rheumatism, pain, cancerous tumors and kin diseases. Bee venom contains a variety of peptides including melittin, apamin, adolapin, the mast – cell-degranulating peptide, enzymes (phospolipase A2), biologically active amines (that is histamine and epinephrine) and nonpeptide components with a variety of pharmaceutical properties.

Cancer treatment
Bee venom has been widely used in the treatment of tumours. Several cancer cells, including renal, lung, liver, prostate, mammary gland as well as leukemia cells can be targets of bee venom peptides such as melittin and phospholipase A2.

In recent study scientists reported that bee venom can induce apoptosis in cancer cells (in human leukemic U937cells) the key regulators in bee venom induced apoptosis are Bcl-2 and caspase-3 through down regulation of the ERK and Akt signal pathway. Melittin, a water-soluble toxic peptide derived from bee venom of Apis mellifera was reported to have inhibitory effects on hepatocellular carcinoma. Melittin inhibits tumor cell metastasis by reducing motility and migration via the suppression of Rac-1 dependent pathway, suggesting that melittin is a potent therapeutic agent for hepatocellular carcinoma. Melittin prevents liver cancer cells metastasis through inhibition of the Rac-1-dependent pathway.

Treatment for rheumatoid arthritis
Bee venom induces apoptosis in rheumatoid synovial cells through a decrease in BCL2 expression and an increase in BAX and caspase-3 expression. Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patients with rheumatoid arthritis.

Controlling diabetes
Hyperglycemia in diabetes leads to increased protein glycation resulting in structural and functional alteration in proteins. Recent studies showed that bee venom prevents glycation induced increasing in beta-sheet structure decreasing in free amino groups, altering in the secondary structure and heme degradation in the hemoglobin. Hence, bee venom has the potential to be used as a natural drug to prevent diabetes complications. Honeybee venom decreases the complications of diabetes by preventing haemoglobin glycation.

Neurodegenerative diseases therapy
Bee venom and its major component, melittin suppress lipopolysaccharide – induced nitric oxide and inducible nitric oxide synthetase expression without causing cytotoxicity in BV2 microglia. Bee venom and melittin also exert anti-inflammatory effects by suppressing the transcription of cyclooxygenase-2 genes and proinflammatory cytokines (TNF-α, IL-6). Thus, bee venom and melittin possess a potent suppressive effect on proinflammatory responses of BV2 microglia, these compounds may also offer substantial therapeutic potential for treatment of neurodegenerative diseases that are accompanied by microglial activation.

Antioxidant
Free radicals are ubiquitous in our body and are generated by physiological processes, including aerobic metabolism and inflammatory responses, to eliminate invading pathogenic microorganisms. Target of free radicals in inflammation include Deoxyribonucleic Acid (DNA)/genetic material, proteins, Ribonucleic Acid (RNA) and lipids. An antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules and so to prevent such changes. Oxidative stress is thought to contribute to the development of chronic and degenerative diseases such as cancer, autoimmune disorders, aging, rheumatoid arthritis, cardiovascular and neurodegenerative diseases. Propolis, pollen, honey have the highest antioxidant activities. Bee venom is a potent antioxidant and possesses radio-protecting actions.

Treatment for HIV
Nanoparticles carrying a toxin found in bee venom can destroy Human immunodeficiency virus (HIV) while leaving surrounding cells unharmed, researchers at Washington University School of Medicine in St. Louis have shown. The finding is an important step toward developing a vaginal gel that may prevent the spread of HIV, the virus that causes AIDS. Bee venom contains a potent toxin called melittin that can poke holes in the protective envelope that surrounds HIV virus as well as other viruses. This melittin is loaded with nanoparticles, which do not harm surrounding normal cells. The nanoparticles attack an essential part of the virus’ structure.

Since melittin attacks double-layered membranes indiscriminately this concept is not limited to HIV. Many viruses, including hepatitis B and C rely on the same kind of protective envelope and would be vulnerable to melittin-loaded nanoparticles. Scientists also said that these nanoparticles are easy to manufacture in large enough quantities to supply them for future clinical trials.

Maggot products
Maggot therapy is now commonly used for many types of infected wounds such as diabetic foot wounds, postoperative infections, bedsores, and leg ulcers, in the United States (US), Israel, and Europe. The larvae of the blowfly, Lucilia sericata, are frequently used although other species have also been tried such as Lucilia cuprina, Phormia regina, and Calliphora vicina. The use of L. sericata larvae for treating wounds has been recognised by the U.S. Food and Drug Administration and the United Kingdom (UK) Prescription Pricing Authority. Sterile maggots can therefore be officially prescribed.

Ant venom as medicine
Ants have been used as medicine, owing to their special active substances such as citral, ATP, histamine, growth hormone, superoxide dismutase etc. Pachycondyla sennaarensis, the samsum ant venom possesses many pharmacological effects as reducing inflammation, relieving pain, inhibition of tumor growth, hepatitis treatment, liver protection. According to Bai et al., solenopsin A, a primary alkaloid obtained from fire ant Solenopsis invicta exhibits antiangiogenic activity; this toxin has the ability to inhibit a series of kinases involving in angiogenesis mechanism.

Polyrachisla mellidens, a medicinal ant used in Chinese medicine, was confirmed to exert potent analgesic and anti-inflammatory actions. Its therapeutic efficacy in the treatment of various inflammatory disorders had been reported.

Beetle products
Many of the Blister beetles (Coleoptera: Meloidae) produce toxic defensive secretions, which upon contact with the skin cause blistering. One such toxin is cantharidin, which has been extracted from Mylabris caragnae, the dried bodies of which have been used in Chinese Folk Medicine since the 13th century for the removal of warts and forever 2000 years for the treatment of cancer.

Canthardin is a monoterpene derived from the bodies of several types of blister beetle, including Mylabris phalerata and M. cichorii (Chinese blister beetles) and this compound is stored in the beetle hemolymph and making up about five per cent of body dry weight. Cantharadin has been found to inhibit the growth of human leukemic cells in vitro. In contrast to other chemotherapeutic agents, cantharadin acts as leukemia progenitor and stem cells.

Several derivatives of cantharadin also retard the growth of prostate, oral, colon, cervical, gall bladder cancer cell lines.

Recently in the year 2007 Huang et al. showed that growth inhibition and killing of human colorectal cancer cells by cantharidin was both time- and dose-dependent. The cantharidin exposure reduced CDK1 kinase activity, which led to failure of the cells to progress from G2 to M phases in the cell cycle. In addition, the colorectal cells were killed by apoptosis, which was induced through the mitochondrial and death receptor pathways and activation of caspases.

Shou et al have studied other effects of cantharidin in human breast cancer cells. They reported that cantharidin resulted in apoptosis and reduced growth, adhesion and migration of the cancer cells.

Wasp venom in cancer therapy
Scientists from the Institute for Biomedical Research (IRB) Barcelona have carried out successful in vitro tests using wasp venom to kill cancer cells. The peptide from wasp venom has the ability to form pores in the cell plasma membrane, penetrate into the cell and finally, cause its death either by necrosis or by triggering apoptosis. However, this powerful natural weapon can not only damage tumor cells but also affect healthy cells. As such the researchers designed a means of transporting the peptide to the tumour and making it accumulate in a specific and controlled manner. The system consists of a decorated carrier polymer with two components: a peptide that is bound to a tumor cell receptor and the cytotoxic peptide of the wasp venom.

In vitro experiments show that the substance is adequately distributed within the tumor cells and causes their death, while healthy cells, such as red blood cells, are not affected.

Wasp venom contains Polybia MPI (from venom of the social wasp Polybia paulista), which shows anti tumour activity. Polybia MPI is able to target non-polar lipid cell membrane, forming ion permeable channels, leading to depolarization irreversible cytolysis and finally cell death. It has been shown that Polybia MPI can significantly inhibit the proliferation of tumor cells and associated endothelial cells by membrane disrupting.

Fujiwara et al. isolated and determined the structure of anti cancer molecule from the outer envelop of the social wasp Vespa simillima. A biologically active quinone, 7,8-seco-para-ferruginone exhibited a growth – inhibitory effect on rat liver cancer cells. The authors suggest that the cytotoxic activity is related to the morphological changes that induce apoptosis of the cells exposed to this molecule.

Medicinal uses of caterpillar venom
There are few studies reporting antitumoral potential of caterpillar venom. Cecropins are group of peptides that were first isolated from the hemolymph of the giant silk moth Hyalophora cecropia. This peptide displays anti-microbial activity and has been used as a potent anti-cancer agent against a variety of tumor cell lines. The mechanism of action of this peptide against tumor cells appears to involve the formation of the pores in the membrane of these cells.

Moore et al. showed that cecropins are active against several mammalian lymphomas and leukemias in vitro and a preliminary in vivo study showed that cecropin B increases the survival time of mice bearing murine ascitic colon adenocarcinoma cells.

Suttmann et al. showed that cecropin A and B inhibit the viability proliferation of bladder cancer cells, but with no effect on fibroblasts. The selective antitumor action mechanism of these peptides depends on disruption of target cell membrane resulting in irreversible cytolysis and cell destruction. Both peptides may offer novel strategies for the treatment of bladder cancer cells with limited cytotoxic effects on benign cells.