Abstract
Lung cancer is the leading cause of cancer-related death in the Unites States, and approximately 85% of all lung cancers are classified as non-small cell lung cancer (NSCLC), which is extremely difficult to treat and its survival rate is low. After decades of clinical trials, the most effective treatments are still those that implement the first-generation platinum anticancer agent cisplatin (CDDP) in combination with other drugs. We previously demonstrated that the naturally-occurring compound phenethyl isothiocyanate (PEITC) can be used to sensitize NSCLC cells to CDDP. Furthermore, co-encapsulation of PEITC and CDDP in liposomes enhances their toxicity toward NSCLC cells. We here optimize liposomal-PEITC-CDDP, demonstrate the release of PEITC and CDDP from the nanoparticle, and show that liposomal-PEITC-CDDP is much more toxic toward both A549 and H596 human NSCLC cell lines than toward WI-38 and BEAS-2B human normal lung cell lines. Thus, we have prepared an efficacious therapy that has significantly higher toxicity toward cancer cell lines than normal cell lines.
Highlights
Lung cancer is the leading cause of cancer-related death in the United States [1]
A Dunnett’s post hoc test accounting for multiple comparisons shows that for both cancer cell lines, the percent survival for the cells treated with a combination of CDDP + phenethyl isothiocyanate (PEITC) is significantly lower than free drug CDDP
A Dunnett’s post hoc test accounting for multiple comparisons shows that for both cancer cell lines, the percent survival of the cells treated with Lipo-PEITC-CDDP is significantly lower than the free drug combination (CDDP + PEITC), as well as liposomal formulations of either single drug (Lipo-CDDP and Lipo-PEITC) (Table 5)
Summary
Lung cancer is the leading cause of cancer-related death in the United States [1]. Approximately 85%. Structural variations among the naturally-occurring ITCs affected their ability to sensitize NSCLC cells to CDDP, and this correlated well with their ability to bind to and, degrade β-tubulin in NSCLC; the ability of benzyl ITC (BITC) is about the same as that of phenethyl ITC (PEITC), both of which are much greater than that of sulforaphane (SFN) [10]. This mechanism may be important for said sensitization. Toxicity was tested in two human NSCLC cell lines, A549 and H596, and compared to its toxicity in human normal lung cells, BEAS-2B and WI-38
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