Home > News > Decoy receptor DcR1 is induced in a p50/Bcl3-dependent manner and attenuates the efficacy of temozolomide

Decoy receptor DcR1 is induced in a p50/Bcl3-dependent manner and attenuates the efficacy of temozolomide

Temozolomide is used widely to treat malignant glioma but the overall response to this agent is generally poor. Resistance to DNA damaging drugs such as temozolomide have been related to the induction of anti-apoptotic proteins. Specifically, the transcription factor NF-kappaB has been suggested to participate in promoting the survival of cells exposed to chemotherapy. To identify factors that modulate cytotoxicity in the setting of DNA damage, we used an unbiased strategy to examine the NF-κB-dependent expression profile induced by temozolomide. By this route, we defined the decoy receptor DcR1 as a temozolomide response gene induced by a mechanism relying upon p50/NF-kappaB1. A conserved NF-kappaB binding sequence (κB-site) was identified in the proximal promoter and demonstrated to be required for DcR1 induction by temozolomide. Loss-of-function and gain-of-function studies revealed that the atypical IkappaB protein, Bcl3, was also required for induction of DcR1 by temozolomide. Mechanistically, DcR1 attenuated temozolomide efficacy by blunting activation of the Fas receptor pathway in p53+/+ glioma cells. Intracranial xenograft studies showed that that DcR1 depletion in glioma cells enhanced the efficacy of temozolomide. Taken together, our results showed how DcR1 upregulation mediates temozolomide resistance, and provided a rationale for DcR1 targeting as a strategy to sensitize gliomas to this widely used chemotherapy.

Does caffeine fight cancer?

Epidemiological studies have shown that caffeinated drinks may help prevent skin cancer by inhibiting a DNA repair pathway, thus killing potentially precancerous cells. In English, it means that drinking drinks containing caffeine will reduce one’s chances of developing some types of cancer, including UV-associated skin cancer. That just proves that caffeine fight cancer. The results, published in the Proceedings of the National Academy of Sciences, lend support to the idea that caffeine could be added to sunblock to increase its protective effects. At the cellular level, they’re showing that caffeine is working in this way of inducing an apoptotic mechanism. This statement was then made by cancer epidemiologist Joanne Kotsopoulos of the University of Toronto.

In the 2007, a study stated that woman who drank caffeinated coffee on a daily basis had a 10 percent lower risk of nonmelanoma skin cancer. Six or more cups of coffee a day translated to a 30 percent reduction in risk. Mouse studies have also confirmed the link, with both ingested and topically-applied caffeine lowering skin cancer rates in the animals. But exactly how the stimulant protected against cancer remained mysterious. One possibility is the drug’s inhibition of ataxia telangiectasia and Rad3-related (ATR), a large protein kinase that senses incomplete DNA replication often a result of DNA damage and signals the cell to not divide. By inhibiting ATR activity, caffeine could make cells more likely to die in response to UV damage, preventing damaged cells from ever becoming cancerous.

Studies have shown that the caffeine molecule acts as a sunscreen. It therefore blocks the penetration of UV rays. And that is why today we see many sunblocks with a good amount of caffeine in them.

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Can sugar consumption cause breast cancer?

A recent study stated that drinking three sugar sweetened drinks a week would increase the risk of having breast cancer. The study had 776 pre-menopausal women and 779 post-menopausal women. Each women’s breast density was assessed by examining their mammograms. The women were told to make a note of sweet they consumed such as chocolates, cakes, ice cream or any sweet drinks. Also they were asked to make a note of how much of spoonful of sugar they add to the drinks.

It was then found out that post-menopausal women who consumed more of sugar, an increase in the density of breast. While the pre-menopausal women observed an increase in breast density when they consumed sugar food. These women, in a week were just consuming three sugar sweetened drinks. The study then further stated that sugar tends to increase the migration of breast cells together. This explains the fact that the premenopausal women who consumed sugar-sweetened drinks were 3 percent more likely to have dense breasts than those who didn’t consume the drinks. And having dense breasts increases your risk of breast cancer by making it difficult to see tumors on mammograms.

However, there is more to be studied on this matter. But until then there is still a link between the sugar consumption and breast density. About 40% of women in the US have dense breast and they are totally unaware of it. Doctors say that women with a dense breast are five time more likely to have a breast cancer and 10 times more likely to miss the tumor in the mammogram test.

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