Beta-lapachone Highly Effective Against Non-small Cell Lung Cancer

A recent report described the molecular mechanism used by the chemotherapeutic agent beta-lapachone to kill non-small cell lung cancer (NSCLC) tumors. NSCLC is one of the deadliest forms of cancer with a five-year survival rate of only about 15%.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) studied the action of beta-lapachone on the enzyme NAD(P)H:quinone oxidoreductase-1 (NQO1). NQO1 is absent or nearly absent in normal tissues but highly expressed in NSCLC tumors.

Results published in the July 3, 2007, online edition of the Proceedings of the [U.S.] National Academy of Sciences revealed that NSCLC cells grown in tissue culture were killed by a high dose of beta-lapachone given for only two to four hours. Normal cells not expressing NQO1 were not damaged by the drug.

Beta-lapachone induced formation of active radicals that caused damage to the cancer cells' DNA while at the same time disrupting the cells' ability to repair their DNA (by inhibiting the DNA repair enzyme topoisomerase I), ultimately leading to the death of the cells. Since treating tumor cells with radiation also causes DNA damage, co-treatment with radiation and beta-lapachone was even more effective than treatment with the drug alone.

"When you irradiate a tumor, the levels of NQO1 go up,” said senior author Dr. David Boothman, professor of pharmacology and radiation oncology at the University of Texas Southwestern Medical Center. "When you then treat these cells with beta-lapachone, you get synergy between the enzyme and this agent and you get a whopping kill. Basically, we have worked out the mechanism of action of beta-lapachone and devised a way of using that drug for individualized therapy.”


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University of Texas Southwestern Medical Center