An HIV Protein and Telomerase Inhibitor Join Forces Against Cancer

Researchers have found a way to specifically kill liver cancer cells and stop tumor growth. In the January issue of Gastroenterology, Guangming Chen et al. report that fusion of a natural inhibitor of telomerase to an HIV protein stops proliferation of hepatocellular carcinoma (HCC) cells and growth of liver tumors in mice.

Cancer cells, especially HCC cells, overexpress the enzyme telomerase, which allows them to extend their chromosome ends and proliferate indefinitely. Telomerase has been investigated as an anti-cancer target because it is required for long-term proliferation of cancer cells and is inactive in most healthy cells. Chen et al. fused part of the protein LPTSan endogenous blocker of telomeraseto the HIV Tat protein, which allowed the fusion protein (called TAT-LPTS-LC) to cross cell membranes and induce telomere shortening, cell crisis (white arrows in figure) and apoptosis of HCC cells (red arrows in figure). TAT-LPTS-LC also reduced the tumorigenicity of HCC cells in mice.

TAT-LPTS-LC shortens cancer cell telomeres to induce cell crisis and apoptosis.

Chen et al. observed the inhibitory effects of TAT-LPTS-LC only in telomerase-positive cells—normal cells were not affected and the fusion protein caused no signs of toxicity in the mice. This might be because normal cells already express LPTS, whereas cancer cells lose it, which allows them to replicate indefinitely; LPTS is reduced or absent in 40%–50% of cases of HCC and other tumor samples.

LPTS (also called PinX1) was the first natural telomerase inhibitor identified. Chen et al. note that although TAT-LPTS-LC suppresses tumor growth effectively, its effects in mice took several weeks, rather than inducing an immediate response. Combinations of telomerase inhibitors and chemotherapeutic drugs might be used to reduce this lag phase and cause rapid and sustained tumor cell death.

Read the article online:
Chen G, Da L, Wang H, et al. HIV-tat–mediated delivery of an LPTS functional fragment inhibits telomerase activity and tumorigenicity of hepatoma cells. Gastroenterology 2011;140:332–343.

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About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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One Response to An HIV Protein and Telomerase Inhibitor Join Forces Against Cancer

  1. Biljna Iliev says:

    Congratulations.I wish you success at research with patients

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