CONCORDIA-LED RESEARCH FINDS FIRST COMPOUND THAT KILLS CANCER CELLS AND EXTENDS LIFESPAN reported/posted by Luciana Gravotta
This is a reporti on the research entitled “Lithocholic bile acid selectively kills neuroblastoma cells, while sparing normal neuronal cells” by Vladimir Titorenko, Professor in the Department of Biology and Concordia University Research Chair in Genomics, Cell Biology and Aging as well as Goldberg, Alexander A. and Beach, Adam and Davies, Gerald F. and Harkness, Troy A. A. and LeBlanc, André and Titorenko, Vladimir I. (2011)
Lithocholic bile acid selectively kills neuroblastoma cells, while sparing normal neuronal cells. Oncotarget . ISSN 1949-2553 Lithocholic acid (LCA), naturally produced in the liver during digestion, has been seriously underestimated. A study published in the journal Oncotarget shows that LCA can kill several types of cancer cells, such as those found in some brain tumors and breast cancer.
| Lithocholic bile acid selectively kills neuroblastoma cells, while sparing normal neuronal cells
Aging is one of the major risk factors of cancer. The onset of cancer can be postponed by pharmacological and dietary anti-aging interventions. We recently found in yeast cellular models of aging that lithocholic acid (LCA) extends longevity. Here we show that, at concentrations that are not cytotoxic to primary cultures of human neurons, LCA kills the neuroblastoma (NB) cell lines BE(2)-m17, SK-n-SH, SK-n-MCIXC and Lan-1. In BE(2)-m17, SK-n-SH and SK-n-MCIXC cells, the LCA anti-tumor effect is due to apoptotic cell death. In contrast, the LCA-triggered death of Lan-1 cells is not caused by apoptosis. While low concentrations of LCA sensitize BE(2)-m17 and SK-n-MCIXC cells to hydrogen peroxide-induced apoptotic cell death controlled by mitochondria, these LCA concentrations make primary cultures of human neurons resistant to such a form of cell death. LCA kills BE(2)-m17 and SK-n-MCIXC cell lines by triggering not only the intrinsic (mitochondrial) apoptotic cell death pathway driven by mitochondrial outer membrane permeabilization and initiator caspase-9 activation, but also the extrinsic (death receptor) pathway of apoptosis involving activation of the initiator caspase-8. Based on these data, we propose a mechanism underlying a potent and selective anti-tumor effect of LCA in cultured human NB cells. Moreover, our finding that LCA kills cultured human breast cancer and rat glioma cells implies that it has a broad anti-tumor effect on cancer cells derived from different tissues and organisms. |
The research team, led by Concordia University, included scientists from McGill University and the Jewish General Hospital’s Lady Davis Institute in Montreal, as well as the University of Saskatchewan. Previous research from this same team showed LCA also extends the lifespan of aging yeast. This time, the team found LCA to be very selective in killing cancer cells while leaving normal cells unscathed. This could signal a huge improvement over the baby-with-the-bathwater drugs used in chemotherapy.“LCA doesn’t just kill individual cancer cells. It could also prevent the entire tumor from growing,” says senior author Vladimir Titorenko, a professor in the Department of Biology and Concordia University Research Chair in Genomics, Cell Biology and Aging.
What’s more, LCA prevents tumors from releasing substances that cause neighboring cancer cells to grow and proliferate. Titorenko says LCA is the only compound that targets cancer cells, which could translate into tumor-halting power.
“This is important for preventing cancer cells from spreading to other parts of the body,” he says, noting that unlike other anti-aging compounds, LCA stops cancer cell growth yet lets normal cells continue to grow.
The next step for the research team, which made its findings in the lab, is to test LCA’s effect on different cancers in mice models. Titorenko expects that LCA will also kill cancer cells in those experiments, which will lead to human clinical trials.
“Our study found that LCA kills not only tumours (neuroblastomas), but also human breast cancer cells,” says Titorenko. “This shows that it has a wide effect on different types of cancers.”
Titorenko emphasizes that unlike drugs used in chemotherapy, LCA is a natural compound that is already present in our bodies. Studies have shown that LCA can be safely administered to mice by adding it to their food.
So why is LCA so deadly for cancer cells? Titorenko speculates that cancer cells have more sensors for LCA, which makes them more sensitive to the compound than normal cells.
LCA sensors send signals to mitochondria — the powerhouses of all cells. It seems that when these signals are too strong, mitochondria self-destruct and bring the cell down with them. Simply put, Titorenko and his colleagues engaged in cancer cell sabotage by targeting a weakness to LCA.
Partners in research:
This study was supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and the Concordia University Research Chair program.
Related links:
• Cited research:
• Concordia Department of Biology
• McGill University
• Lady Davis Institute at the Jewish General Hospital
• University of Saskatchewan
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