Drugs from poison

Biplab Das

doi:10.1038/nindia.2010.175 Published online 14 December 2010

From microbes to men, all living organisms have one thing in common. They all have innate systems that secrete toxins — some to attack, some to defend. Recent research shows that these toxins can yield drug molecules that have potential to combat diseases such as cancers and arthritis.

Some speakers at the conference: P. Gopalakrishnakone & (inset L to R) Glenn F. King, Jayanta Kumar Mishra.

A national conference on toxins discussed the beauty of this process of churning therapies out of deadly toxins. The meet on animal, microbial and plant toxins and snakebite management, jointly organized by Indian Institute of Chemical Biology and KPC Medical College and Hospital during December 11-12, 2010, was the first such international gathering of toxin experts in the country.

Though the most studied toxic protein in snake venom — phospholipase A2 (PLA2) — took centrestage, researchers attending the meet reported interesting new proteins that promise to cure diseases. "One such protein is phospholipase inhibitor from python (PIP)," P. Gopalakrishnakone from the National University of Singapore pointed out. The protein plays a significant role in modulating inflammation.

"Studies with rats show that peptides designed from PIP suppress the activity of the enzyme metalloproteinase-1 (MMP-1) and PLA2 that have roles in inflammatory diseases," Gopalakrishnakone told the conference. This provides new therapeutic options in the treatment of inflammatory diseases such as arthritis and cancer, he added.

In the see-saw battle between human and cancers, snake venom toxins seem a potent source of therapies. "We have identified anti-cancer protein toxins in Indian cobra (Naja kaouthia) and Indian viper (Daboia russelli)," said Antony Gomes from the department of Physiology, University of Calcutta. These protein toxins have shown efficacy against blood, brain, and ovarian cancers. Even some of these toxins showed anti-arthritic activity.

Of all venoms, snake venom has the most severe toxic effects claming lives within minutes to hours. Snake venom contains a host of toxic proteins that damages nerve cells as well as other cells. "Among the toxins, the most studied protein is phospholipase A2 (PLA2), an enzyme that binds to membrane lipid," said T. Veerabasappa Gowda from the JSS College of Arts, Commerce and Science, Mysore. PLA2 are commonly found in mammalian tissues as well as insect and snake venom.

Besides the snake, another venomous animal is the spider. "Spiders are the most successful venomous animals with around 100,000 species," said Glenn F. King from the University of Queensland, Australia. Some of the spider species produce venom containing more than 1000 unique peptides. Spider venom peptides are remarkably stable and are being developed commercially as bioinsecticides for the control of crop pests and disease vectors such as mosquitoes, King said.

The humble toad also offers some therapeutic toxins. Epithelial cancers including colorectal cancers increase with aging. "These diseases are driven by self-renewing cancer stem cells (CSC). Aging increases the susceptibility to carcinogens that promotes the appearance of CSC," said Adhip P. N. Majumder from the Wayne State University School of Medicine, Michigan, USA.

"We have shown that curcumin in combination with a crystalline compound called BM-ANF-1 isolated from the purified skin extract of Indian common toad (Bufo melanostictus) inhibits the growth of colon cancer cells," Majumder reported.

The seas teeming with life forms were recognised as a treasure trove of potential drug molecules. "The unique ocean environment is home to microorganisms, invertebrates, vertebrates, phytoplankton and sea weeds that possess molecules of unique chemical features," said Jayanta Kumar Mishra from the Pondicherry University.

Researchers have identified anti-cancer and anti-inflammatory agents from sponges. Sea urchins found along the rocky coasts of Andaman & Nicobar Islands show anti-microbial property, Mishra said.