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Aberrant arachidonic acid (AA) metabolism has been involved in inflammation and carcinogenesis. The key enzymes in AA metabolism such as cytosolic phospholipase A2 (cPLA(2)) and cyclooxygenase-2 (COX-2) have been implicated in the development and progression of many human cancers, including lung cancer. Hence, the blockade of these enzymes may suppress promotion and survival of human cancer cells. We and others have shown that a natural triterpenoid, pachymic acid (PA), can exhibit antiinflammatory and anticancer properties; however, its potential mechanism has not been fully clarified. In this study, we examined the effect of PA on the proliferation of human nonsmall cell lung cancer A549 cells. Furthermore, we investigated the influences of nontoxic levels of PA on AA metabolism. Additionally, the cellular events and signal transduction pathways influenced by PA were also examined. Our results showed that PA (1) inhibited anchorage-dependent and -independent A549 growth in a concentration-dependent manner, (2) induced apoptosis and disrupted mitochondrial membrane potential in A549 cells, and at nonlethal levels, (3) decreased IL-1 beta-induced activation of cPLA(2) and COX-2, (4) suppressed IL-1 beta-induced activation of mitogen-activated protein kinases (MAPKs), and (5) inhibited IL-1 beta-stimulated nuclear factor kappa B (NF-kappaB) signaling pathways. We speculate that inhibition of AA metabolism by PA is mediated in part by its inhibition of MAPKs and NF-kappaB signaling pathways. Our study reveals that, apart from its cytotoxic effect, PA has the chemopreventive potential by reducing production of eicosanoids from AA metabolism.

Lung cancer continues to be the leading cause of cancer-related mortality worldwide. This warrants the search for new and effective agents against lung cancer. We and others have recently shown that lanostane-type triterpenoids isolated from the fungal species Poria cocos (P. cocos) can inhibit cancer growth. However, the mechanisms responsible for the anticancer effects of these triterpenoids remain unclear. In this study, we investigated the effect of polyporenic acid C (PPAC), a lanostane-type triterpenoid from P. cocos, on the growth of A549 nonsmall cell lung cancer cells (NSCLC). The results demonstrate that PPAC significantly reduced cell proliferation via induction of apoptosis as evidenced by sub-G1 analysis, annexin V-FITC staining, and increase in cleavage of procaspase-8, -3, and poly(ADP-ribose)-polymerase (PARP). However, unlike our previously reported lanostane-type triterpenoid, pachymic acid, treatment of cells with PPAC was not accompanied by disruption of mitochondrial membrane potential and increase in cleavage of procaspase-9. Further, PPC-induced apoptosis was inhibited by caspase-8 and pan caspase inhibitors but not by a caspase-9 inhibitor. Taken together, the results suggest that PPAC induces apoptosis through the death receptor-mediated apoptotic pathway where the activation of caspase-8 leads to the direct cleavage of execution caspases without the involvement of the mitochondria. Furthermore, suppressed PI3-kinase/Akt signal pathway and enhanced p53 activation after PPAC treatment suggests this to be an additional mechanism for apoptosis induction. Together, these results encourage further studies of PPAC as a promising candidate for lung cancer therapy.

Ultrasound is best known for its imaging capability in diagnostic medicine. However, there have been considerable efforts recently to develop therapeutic uses for it. The purpose of this review is to summarize some of the recent advances made in the area of therapeutic ultrasound as they relate to drug delivery. In particular, this review will focus on the applications of ultrasound to enhance the delivery and effect of three distinctive therapeutic drug classes: chemotherapeutic, thrombolytic, and gene-based drugs. In addition, ultrasound contrast agents have been recently developed for diagnostic ultrasound. New experimental evidence suggests that these contrast agents can be used as exogenous cavitation nuclei for enhancement of drug and gene delivery. Thus, brief review of this new class of agents and their roles in drug delivery will also be provided. By comparison to diagnostic ultrasound, progress in therapeutic use of ultrasound has been somewhat limited. The recent successes in ultrasound-related drug delivery research positions ultrasound as therapeutic tool for drug delivery in the future. © 2002 John Wiley & Sons, Inc. Med Res Rev, 22, No. 2, 204–223, 2002; DOI 10.1002/med.10004

Until recently it was believed that opioid uptake was mediated by passive diffusion; however, we recently demonstrated that brain: plasma partitioning of fentanyl reduced by verapamil, likely by in...