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Betel Nut - The Chewing Package that activates a Precancerous Oral Disease

Photo: Siddharth Kankaria

The traditional Asian chewing package used in marriages for symbolising heavenly love, is no longer having its heavenly charm according to a new research. Areca nut, packed with betel leaves and slaked lime, is an important chewing dessert in many Asian cultures. Its usage to cure indigestion and impotence dates back to first century AD and it is still being consumed by around 700 million people in the tropics for its psychoactive and brain stimulating properties. However, studies have indicated that several chemical compounds present in areca nut are carcinogens and its usage has been linked to oral cancers. Now a new study points at a detailed pathway on how chewing areca nut causes a precancerous condition.

In a recent study, scientists from the Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science (IISc), Bangalore, and the Department of Oral and Maxillofacial Surgery, D.A Pandu Memorial- R.V Dental College and Hospital, Bangalore, have explained the role of areca nut in causing a precancerous disease condition called Oral Submucous Fibrosis (OSF). Fibrosis is a disease wherein excess depositions of extra cellular proteins (collagens, fibronectins, etc) are observed. OSF is an inflammatory condition in the oral sub mucosa tissue caused by prolonged chewing of areca nuts.

Previous studies have reported that chewing areca nut caused OSF by activating an important signalling pathway called TGF-β (Transforming Growth Factor Beta) in the oral tissues. However, until now not much was known about how this exactly occurred inside the cells. This study demonstrates how the signalling is activated with areca nut in epithelial cells.

“Transforming Growth Factor beta is a growth factor secreted by several types of cells in various contexts. This factor plays a role in various physiological processes like cell development, differentiation, immune function, wound healing, etc. However, some imbalance in the expression of this factor leads to pathology, fibrosis in various organs being the best known example. There is enormous evidence to suggest its implication in cancer progression”, explains Prof. Paturu Kondaiah from the Department of Molecular Reproduction, Development and Genetics, IISc.

The researchers studied the mechanism of activation of TGF-β pathway in two types of epithelial cells. It is well-known that fibrosis occurs due to activation of the fibroblast cells. “Activation of the fibroblasts is a process that brings about a change in the functionality of the fibroblasts. Although exact mechanisms are not clearly understood, several factors such as TGF-β have been shown to bring this change. Such a change results in the excess production and secretion of fibrosis related molecules such as collagens, fibronectins, etc”, says Prof. Kondaiah. Based on this, the researchers hypothesised that TGF-β secreted from epithelial cells can be considered as an important component needed for the activation of fibroblasts.

Interestingly, the researchers observed the presence of TGF-β2 protein within two hours of exposing epithelial cells to areca nut. They have also shown, for the first time, the involvement of a bunch of molecules responsible for TGF-β pathway activation in OSF. “We studied the effect of areca nut on cell lines with respect to gene expression, signalling pathway activation, etc. Some of these results have been compared with the diseased tissues and are found comparable. We feel that there are good reasons for the extrapolation”, says Prof. Kondiah on the results of the study.

What can be done to caution people about the ill-effects of chewing areca nut? “This is a public health issue. Due to the ill effects of chewing areca nut/gutka, these are banned in some states. The government should frame a policy on advertisements and distribution of these products. More and more public awareness should be advocated”, recommends Prof. Kondaiah. If science works hand in hand with cultural awareness, cures for many deadly lifestyle based diseases can be achieved sooner than expected.

About the paper:

The paper was published in Nature Scientific Reports http://www.nature.com/articles/srep34314

About the authors:

Prof. Paturu Kondaiah and Ms. Ila Pant (The first author of the paper) are from the Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore

Mr. Girish Rao (The second author of the paper) is from Department of Oral and Maxillofacial Surgery D.A Pandu Memorial- R.V Dental College and Hospital Bangalore

Contact information:

Prof. Paturu Kondaiah

E mail ID: paturu@mrdg.iisc.ernet.in