Anisur Rahman Khuda-Buksh, a biologist from Beldanga near Murshidabad, was troubled by the plight of Bengal’s rural folk exposed to arsenic-contaminated groundwater. To find a solution, five years ago he turned to plant compounds.

His research may now have unravelled the cascade of biological mechanisms through which a compound called gingerol, extracted from the roots of the ginger plant, can kill cancerous cells.

“Gingerol seems to coax cancer cells to go into a self-destruct mode —cancer cells exposed to gingerol kill themselves,” said Khuda-Buksh, professor of zoology at the University of Kalyani, which is about 50km north of Calcutta.

Through experiments on clusters of cervical cancer cells maintained in laboratory vials, Khuda-Buksh and his colleagues have determined the genetic switches that gingerol turns on or off to kill tumour cells.

Their findings appeared last week in the European Journal of Pharmacology. “We’re hoping this will help in the design of new chemotherapy strategies,” Khuda-Buksh said.

While many other compounds can kill cancer cells and are used in chemotherapy, the problem is that these substances are toxic to healthy cells too. Since gingerol is derived from a spice that is used in most Indian kitchens daily, scientists expect gingerol-based therapy to be relatively safe for normal cells.

“These are exciting results and they open up an additional avenue for using natural products as anti-cancer agents,” said Srikumar Chellappan, professor and chair of tumour biology at the H Lee Moffitt Cancer Centre and Research Institute, in Tampa, Florida, the US. “While chemopreventive agents from natural sources such as curcumin [from turmeric], cucurbitacin [from bitter gourd], or resveratrol [from grapes] can selectively kill cancer cells by affecting the activity of various cellular proteins, gingerol appears to induce cell death by an unusual mechanism,” Chellappan said.

Khuda-Buksh selected the ginger plant after reading research papers on gingerol published earlier by other scientists.

Yogeshwar Shukla, molecular biologist at the Indian Institute of Toxicology Research, Lucknow, is one such scientist who reported that gingerol has anti-inflammatory and anti-cancer effects. “Ginger is widely used in traditional medicine, so we decided to study its biological effects,” said Shukla. In two sets of earlier experiments, Shukla and his colleagues demonstrated that gingerol can kill prostate cancer cells and skin cancer cells maintained in laboratory glassware. Then, two years ago, they showed that mice that are exposed to benzopyrene — a carcinogen that causes skin cancer — appeared to be protected from the cancer when administered gingerol.

Khuda-Buksh and his colleagues studied the effects of gingerol on a type of cervical cancer cell used worldwide for cancer research. Their experiments suggest that gingerol initiates a cascade of reactions inside cancer cells that leads to the release of an enzyme called caspase within cancer cells, which directs the cells to self-destruct through a process called apoptosis.

The health of normal cells is guided by, among other things, a fine balance of genes that drive the cell towards apoptosis and draw the cell away from apoptosis.

In cancer cells, the genetic pathway that drives the cell towards apoptosis is impaired or shut down — and the cells become immortal.

The experiments by the Kalyani researchers suggest that gingerol activates pro-apoptotic genes and suppresses anti-apoptotic genes. For example, gingerol inside tumour cells was observed to suppress an anti-apoptotic gene called bcl-2 and cause the over-expression of a pro-apoptotic gene called bax, thus pushing the cell towards cellular suicide.

Scientists, including Khuda-Buksh himself, caution that in-depth biological studies in animal models would be required to assess the toxicity and efficacy of the compound before it can move towards clinical research in humans.

One line of future research would be efforts to develop more active derivatives of this natural product which are effective at lower doses, said Chellappan, who is himself involved in the search for novel anti-cancer agents, but was not associated with the work at Kalyani.

“The development of novel drugs based on gingerol is likely to be a long and tedious process, but it has the potential to be used as a chemopreventive agent — as has been suggested for resveratrol, the active component of grapes that is supposed to give the health benefits of red wine,” said Chellappan. “This work raises the possibility that ginger in diet might have chemopreventive effects — but even this will need more studies.”