Viagra way for cancer

What scientists have done with a substance that the body uses to signal an erection may give humanity a whole new way of tackling stubborn cancers.

A team of scientists, including the Calcutta-born Rajdeep Chowdhury, has found that nitric oxide — a molecule that helps blood vessels to dilate and which is also used in muscle building — packs yet another surprise. The chemical can trigger a cascade of molecular events that eventually lead to the destruction of cancer cells that refuse to respond to the present-day anticancer drugs.

Nitric oxide is known to be a key signalling molecule in the human body. For instance, drugs used to treat erectile dysfunction such as Viagra copy the action of nitric oxide.

Most cancer drugs directly or indirectly make use of an inherent mechanism that forces defective cells to commit suicide. This is called apoptosis, or programmed cell death. However, many cancers of the breast and the pancreas do not respond well to such treatment.

Two researchers in the US — Gerald N. Wogan of the Massachusetts Institute of Technology and Cheryl Lyn Walker of the Texas A&M Health Science Center in Houston — have collaborated to show for the first time that yet another natural mechanism called autophagy can be harnessed to tame such malignant cells.

Interestingly, two Indian postdoctoral researchers — Chowdhury in Wogan’s lab and Durga Nand Tripathi in the Walker lab — are the joint first authors of the paper, published in the Proceedings of National Academy of Sciences last week.

Durga Nand Tripathi and Rajdeep Chowdhury

Autophagy is a process whereby a cell consumes parts of itself so that its integrity is maintained. This self-eating process helps the cells to clean up abnormal lumps of proteins as well as damaged sub-cellular constituents.

This phenomenon also comes into play when a person is starving — when food is not available, the body starts breaking down fat cells so that it can keep itself alive.

“What is significant is that we found out that nitric oxide pushes the cancer cell not towards apoptosis but autophagy,” says Chowdhury, currently an assistant professor at the Birla Institute of Technology and Science at Pilani, Rajasthan.

“We have unravelled the molecular involved in this process. We hope that this might open a new avenue to deal with rogue cancer cells ,” says Chowdhury who did his schooling in Calcutta and earned a PhD from the city-based Indian Institute of Chemical Biology.

Tripathi points out that resistant cancers have been giving scientists a tough challenge for some time. “For instance, apoptosis cannot be an option for certain breast and pancreatic cancers because of two biomolecules. When the protein PCL2 is present in high levels, the cells cannot be subjected to programmed cell death. On the other hand, low levels of the enzyme capsase3 come in the way of destroying the tumour cells,” says Tripathi, who moved to the US in 2010 after obtaining a doctorate from the National Institute of Pharmaceutical Education and Research at Mohali, near Chandigarh.

Free radicals like reactive oxygen species are produced in the body as part of the metabolic process. When they combine with nitric oxide, much stronger reactive nitrogen species are produced. These molecules can induce autophagy by activating a protein called ATM, whose primary job is to repair damage caused to DNA, Tripathi says.

But when its efforts to repair the damage fail, it signals the protein machinery of the cell to prepare it for autophagy. As part of autophagy, mitochondria — which is responsible for supplying energy in the cell — is attacked. “It is just like shutting down the energy supply in the cell,” Tripathi told KnowHow.

The scientists next plan to study what sort of impact this process will have on normal cells around tumour cells.

“This work describes a new self-destruction mechanism that can be exploited to treat cancer, particularly the resistant types,” says Rathindranth Baral, a senior scientist at the Chittaranjan National Cancer Institute, Calcutta.

More importantly, this process can be initiated by nitric oxide whose production is less expensive than standard cancer treatment, Baral adds. He hopes that further studies by different research groups will validate the efficacy of this process, helping the scientific community to develop novel, non-toxic cancer therapies.