Curcumin aid for oral cancer
doi:10.1038/nindia.2010.124 Published online 13 September 2010
Researchers have synthesized hydrazinocurcumin, a curcumin-derived water-soluble compound that halts the growth of oral cancer cells. The compound stops the modification of an enzyme called histone acetyltransferase (HAT), which in turn modifies histone protein. When combined with DNA, histone makes chromatin, the building block of chromosome.
When this enzyme modification goes into overdrive, it triggers various diseases and turns on specific cancer genes that are involved in the manifestation of oral cancer. The curcumin-derived compound therefore looks promising as a potential candidate for fighting oral cancer.
Oral cancer starts with inflammation and increased levels of nitric oxide in the mouth. Nitric oxide triggers a cascade of chemical events that lead to the production of two proteins — NPM1 and GAPDH. These proteins bring about changes in p300 — a type of HAT enzyme — which further modifies H3, a specific type of histone protein. This activates several cancer-promoting genes, and thus leads to oral cancer.
The therapeutic efficacy of compounds that inhibit the activity of HAT has been successfully explored for HIV and cardiac diseases. To find out how the curcumin-derived compound disrupts HAT activity in cancer, the researchers took mice with weak immune systems and grew in them oral cancer cells isolated from patients. These mice were then treated with the compound.
The researchers found that the tumours were around 50% smaller in the treated mice than the untreated ones. The treated mice also showed lower levels of GAPDH and NPM1. The compound brought about senescence-like growth arrest in oral cancer cells, which is known to contribute to treatments such as chemotherapy and ionization radiation.
"This therapeutic option for combating oral cancer could be an important strategy as it is one of the most predominant killer cancers in Indian subcontinent," says lead researcher Tapas K. Kundu. The compound was also found to be non-toxic in mice, he adds.
The authors of this work are from: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur and Bangalore Institute of Oncology, Bangalore, Karnataka, India.