Abstract
Lung cancer is the leading cause of cancer-related death in the United States, and it is estimated more than 220,000 new cases will be diagnosed in 2011. The first-line therapy for advanced lung cancer almost always contains a platinum-based chemotherapeutic agent, regardless of the disease's histological profile. In vitro studies have shown that isothiocyanate compounds can sensitize lung cancer cells to cisplatin treatment, however the underlying mechanisms have not been well defined and until now, there have been no in vivo demonstrations to support the in vitro results. Our lab recently discovered that allyl isothiocyanate (AITC), a naturally occurring isothiocyanate molecule found in cruciferous vegetables such as horseradish and mustard seeds, can sensitize lung cancer cells to cisplatin treatment. Our data demonstrate that the combination of cisplatin and AITC can induce apoptosis more effectively than cisplatin alone. Furthermore, drug combination index (CI) analysis from cancer cell-based ex vivo studies showed synergistic effects between AITC and cisplatin in defined dose ranges. Mechanistic studies revealed that combination treatment of cisplatin and AITC decreases the expression of survivin and Bcl-2 and concomitantly increases caspase-3 activation, PARP cleavage and DNA fragmentation, hallmarks of apoptosis. Most importantly, our data demonstrate that cisplatin, in combination with orally administered AITC, shows significantly improved suppression of lung tumor growth in human lung tumor xenograft mouse models compared to cisplatin or AITC alone. Given its oral bioavailability and potential to overcome cisplatin resistance, AITC shows promise as a chemotherapeutic-sensitizer for the treatment of advanced lung cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3726. doi:1538-7445.AM2012-3726
