Photosensitized co-generation of nitric oxide and singlet oxygen Enhanced toxicity against ovarian cancer cells.

Near micromolar concentrations of nitric oxide (NO) induce tumor cells death. However, an appropriate NO load has to be delivered selectively to the tumor site in order to avoid NO loss and secondary NO-induced effects. The encapsulation of millimolar concentrations of a NO source and an appropriate trigger of NO release within phospatidylcholine-based liposomes should provide an efficient tool for the selective release of the needed NO payload. In this work we report the photosensitized generation of singlet oxygen and NO from folate-targeted PEGylated liposomes, containing AlPcS4 as the sensitizer and S-nitrosoglutathione (GSNO), in millimolar amounts, as the NO source. Amounts of singlet oxygen detected outside the liposome when using PEGylated liposomes are near 200 % larger when GSNO is present inside the liposomes as compared to its absence. These liposomes, conjugated to folate, were found to enhance the photosensitized cytotoxicity to A2780CP20 ovarian cancer cells as compared to liposomes containing the sensitizer but no GSNO (30 % as compared to 70 % cell viability) under the conditions of this work. Fluorescense of AlPcS4 was observed inside cells incubated with folate-conjugated liposomes but not with liposomes without folate. The photosensitized activity enhancement by GSNO increased when light fluence or liposome concentration were increased. The majority of ovarian cancer patients are initially diagnosed with disseminated intra-abdominal disease (stages III-IV) and have a 5-year survival of less than 20%. This work suggests a novel ovarian cancer nodules treatment via the use of tumor-targeted liposome nanoparticles with the capability of generating simultaneously reactive oxygen and nitrogen species upon illumination with near-infrared light.

Simalikalactone D, a Potential Anticancer Compound from Simarouba tulae, an Endemic Plant of Puerto Rico.

Species of the genus Simarouba have been studied because of their antimalarial and antileukemic activities. A group of oxygenated terpenes called quassinoids have been isolated from species of the Simarouba genus, and are responsible for its therapeutic properties. We hypothesized that Simarouba tulae, an endemic plant from Puerto Rico, is a natural source rich in quassinoid compounds with anticancer activity. The leaves were processed and extracted with solvents of different polarities. The extracts were screened for their antiproliferative activity, and it was shown that the chloroform extract was the most active extract. This extract was purified using different chromatographic techniques to afford the quassinoid simalikalactone D (SKD). This compound was further characterized using NMR and X-ray diffraction analysis. A reassessment of original structural assignments for SKD is proposed. SKD showed high cytotoxicity activity, with an IC50 of 55, 58, and 65 nM in A2780CP20 (ovarian), MDA-MB-435 (breast), and MDA-MB-231 (breast) cell lines, respectively. Exposure to SKD led to 15% inhibition of the migration of MDA-MB-231 cells.