Reduced Cancer Cell Growth Research Articles

A Role for the G12 Family of Heterotrimeric G Proteins in Prostate Cancer Invasion

Many studies have suggested a role for the members of the G12 family of heterotrimeric G proteins (Galpha12 and Galpha13) in oncogenesis and tumor cell growth. However, few studies have examined G12 signaling in actual human cancers. In this study, we examined the role of G12 signaling in prostate cancer. We found that expression of the G12 proteins is significantly elevated in prostate cancer. Interestingly, expression of the activated forms of Galpha12 or Galpha13 in the PC3 and DU145 prostate cancer cell lines did not promote cancer cell growth. Instead, expression of the activated forms of Galpha12 or Galpha13 in these cell lines induced cell invasion through the activation of the RhoA family of G proteins. Furthermore, inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) in the PC3 and DU145 cell lines did not reduce cancer cell growth. However, inhibition of G12 signaling with p115-RGS in these cell lines blocked thrombin- and thromboxane A2-stimulated cell invasion. These observations identify the G12 family proteins as important regulators of prostate cancer invasion and suggest that these proteins may be targeted to limit invasion- and metastasis-induced prostate cancer patient mortality.

In vitro investigation of lipid implants as a controlled release system for interleukin-18

Operating on the inductive and effective phases of an anti-tumor immune response and uncovering pivotal functions that may reduce cancer cell growth, interleukin-18 (IL-18) appears to be an attractive candidate for the sustained local adjuvant immunotherapeutic treatment of brain gliomas. The objective of this work was to develop IL-18 loaded lipid implants as a controlled delivery system. For the preparation of protein loaded triglyceride matrix material, a solid-in-oil (s/o) dispersion technique was chosen for which protein particles in the micrometer range were first prepared by co-lyophilization with polyethylene glycol (PEG). Implants of 1 mm diameter, 1.8 mm height and 1.8 mg weight were manufactured by compression of the powder mixture in a specially designed powder compacting tool. The in vitro release behavior of 125I-Bolton-Hunter-radiolabeled IL-18 was assessed in a continuous-flow system. A cell culture assay was established for the determination of bioactivity of released IL-18. Implants showed a continuous release of 10–100 ng IL-18 per day for 12 days. A progressive integrity loss was observed with ongoing release, which would be related to protein degradation during incubation. The initially released fraction proved complete retention of bioactivity, indicating that the manufacturing procedure had no detrimental effects on protein stability.

Effects of herbal preparation Equiguard™ on hormone-responsive and hormone-refractory prostate carcinoma cells: Mechanistic studies

The Equiguard is a dietary supplement comprised of standardized extracts from nine herbs, respectively, Herba epimedium brevicornum Maxim (stem and leaves), Radix morindae officinalis (root), Fructus rosa laevigatae michx (fruit), Rubus chingii Hu (fruit), Schisandra chinensis (Turz.) Baill (fruit), Ligustrum lucidum Ait (fruit), Cuscuta chinensis Lam (seed), Psoralea corylifolia L. (fruit), and Astragalus membranaceus (Fisch.) Bge (root). This proprietary product, formulated according to Chinese traditional medicinal concepts, is aimed at restoring harmony in the <primordial (original) ying-yang> of the kidney, an organ which Chinese medicinal principles consider to be vital for invigorating as well as maintaining balance of the entire urological system. As the prostate is an integral component of the urological system, we performed in vitro studies to test the effects of ethanol extracts of Equiguard to modulate prostate growth and gene expression. These studies used prostate cancer cells mimicking the androgen-dependent (AD) and androgen-independent (AI) states of prostate carcinogenesis. Results show that Equiguard significantly reduced cancer cell growth, induced apoptosis, suppressed expression of the androgen receptor (AR) and lowered intracellular and secreted prostate specific antigen (PSA), and almost completely abolished colony forming abilities of prostate cancer cells. These data support the interpretation that this herbal formulation contains ingredients that collectively may be efficacious in preventing or treating AD and AI prostate carcinoma. The anti-prostatic activities of Equiguard may stem from its complex composition capable of targeting multiple signal transduction/metabolic pathways, to effectively correct, counteract or circumvent the impaired or dysfunctional mechanisms accompanying different stages of prostate carcinogenesis.