Great gambler: Dr Bhudev Das and his co-researcher in their laboratory

The yellow ingredient of turmeric has long been hailed by medical scientists for its promise as an anti-infective, anti-inflammatory, and anti-tumour agent. Five years ago, biologist Bhudev Das convinced the department of biotechnology (DBT) to fund an attempt to pit this household spice against the sexually-transmitted human papilloma virus (HPV) that can cause uterine and cervical cancer, the most common cancer among Indian women. The gamble appears to have worked.

A study by Das and his student Bhupesh Prusty has now shown that curcumin, the substance that imparts turmeric its colour, may help fight the HPV. The finding has raised hopes among scientists for a novel treatment to tackle the HPV which infects an unknown number of women across India each year. Tens of thousands among them develop cervical cancer years later. Now Das and Prusty have shown that curcumin can make the HPV lurking inside cervical cancer cells inactive and arrest the cancer.

In their first-floor laboratory at the Institute of Cytology and Preventive Oncology (ICPO) near New Delhi, the devastating effect of curcumin on the virus becomes apparent in an experiment that takes just 24 hours. Prusty picks up a flask, the size of a large matchbox, containing a clear red solution and a million cervical cancer cells infected with the HPV. The virus has commandeered the genomes of the human cells inside the flask ? the cervical cancer cells are producing HPV proteins.

Prusty pours some drops of curcumin into the flask. A day later, none of the cervical cancer cells are producing viral proteins. The viral genes that had fused with the human genes inside the cervical cells have been silenced.

?Curcumin blocks expression of the viral genes. They remain in the human cells but, now, only as harmless genome fragments,? says Prusty. The finding has been accepted for publication in a forthcoming issue of the International Journal of Cancer.

When the HPV enters the female reproductive tract, mainly through sexual activity, it colonises cells of the uterine cervix ? the neck of the uterus. Although the HPV is eliminated by the immune system in the majority of women, it continues to lurk in a small fraction and, studies show, these women are at a high risk of developing cervical cancer. It is a slow process, triggered by the entry of the virus. The researchers hope that inactivating the HPV with curcumin can arrest the cancer.

ICPO director Das says that the idea of trying out curcumin against the HPV came to him after he studied the action of a synthetic compound called PDTC against HPV-infected cells. ?Curcumin has been used for centuries and consumed daily,? says Das. ?We expect th-at this herbal product would have a lower risk of side-effects than synthetic compounds.?

When the HPV enters a cervical cell, it fuses its own genome with that of the host cell and makes it produce viral proteins. Two such proteins, E6 and E7, place the cell on course to developing cancer. These proteins bind to protein products of human P53 and Rb genes, which suppress tumours. The P53 and Rb are guardians of the genome. Any renegade cell that begins to slip towards cancer is destroyed through a process called apoptosis, or ?cellular suicide,? initiated by the tumour suppressor genes like P53 and Rb.

The E6 and E7 binding to P53 and Rb interferes with the normal functions of the tumour suppressors. The ICPO studies show that curcumin prevents the production of E6 and E7 by the HPV-infected cells.

?The curcumin blocks the activity of another protein which leads to suppression of E6 and E7,? says Das. In the absence of these viral proteins, the P53 and Rb in the infected cells begin to work normally and the cells are free to commit suicide.

?While the anti-tumour and anti-viral properties of curcumin have been known for a long time, this study points to a specific mechanism of action by which curcumin can act against the HPV,? says Dr Devarajan Karunagaran, a scientist at the Rajiv Gandhi Centre for Biotechnology in Thiruvanthapuram, who has himself been studying the biological effects of curcumin for several years.

Das cautions that it is still uncertain how long the curcumin acts to block E6 and E7 and whether the viral activity will return once the curcumin is used up.

The ICPO researchers have sought permission for clinical trials of curcumin as a therapeutic agent against women with cervical cancer infected with the HPV. A decision on the clinical trials is expected to come soon because curcumin is a traditional herbal product. The Institute has approached a leading pharmaceutical company for production of large quantities of high-quality curcumin for a human trial.

?The formulation may be a tablet to be placed at the cervix for the slow release of the curcumin in the region of the infected cells,? says Das. Whether it will work and ? if it does ? just how much curcumin will have to be used are questions that only clinical trials will answer.