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Over 2 million Americans are currently living with prostate cancer. Current chemotherapeutic strategies are only partially effective in controlling the disease. There is always a need for an effective newer drug for treating prostate cancer. Use of active principles from medically important herbs has proven to be effective in treating various forms of cancers. Glycyrrhizin, a triterpene compound isolated from roots of licorice has been found to exhibit potent in vitro cytotoxic activity against several human cancer cell lines. In this study, we evaluated the effects of glycyrrhizin on the viability of two human prostate cancer cells LNCaP (hormone-dependent) and DU-145 (hormone-independent) in vitro. Cell viability assay showed that glycyrrhizin inhibited the cell proliferation of prostate cancer cells in a time- and dose-dependent manner. The decreased viability of prostate cancer cells was due to apoptosis as confirmed by Annexin-V FITC flow cytometric analyses. Glycyrrhizin also caused DNA damage in DU-145 and LNCaP cells in a time-dependent manner. Caspase-3 and -8 activities were not detected in glycyrrhizin-treated prostate cancer cells suggesting that caspase-independent pathways may be involved in the apoptotic mechanism. Collectively, these studies suggest that glycyrrhizin has therapeutic potential against prostate cancer.

Patients who survive critical illness are at risk of permanent physical and functional deficits which decrease the health-related quality of life. The reasons for physical morbidity include the nature of and treatment for the inciting critical illness, new decrements in organ function and worsening of pre-existing organ dysfunction, and prolonged physical immobility and long intensive care unit stay.

Immunization of jirds with Bm-alt-2 elicited partial protection against challenge infection with the filarial parasite Brugia malayi. In this study, we initially compared the protective immune responses elicited following immunization with recombinant Bm-ALT-2 protein regimen and Bm-alt-2 DNA regimen. These studies showed that protein vaccination conferred approximately 75% protection compared to DNA vaccination that conferred only 57% protection. Analysis of the protective immune responses showed that the protein immunization promoted a Th2-biased response with an increase in IL-4, IL-5 and IgG1 responses, whereas, the DNA vaccine promoted a Th1-biased response with profound IFN-gamma and IgG2a responses. Since protein vaccination gave better results than DNA vaccination, we then wanted to evaluate whether a prime-boost vaccination that combined DNA prime and protein boost will significantly increase the protective responses induced by the protein vaccine. Our results suggest that prime-boost vaccination had no added advantage and was comparatively less effective (64% protection) than the Bm-ALT-2 protein alone vaccination. Prime boost vaccination generated mixed Th1/Th2 responses with a slightly diminished Th2 responses compared to protein vaccination. Thus, our results suggest that Bm-ALT-2 protein vaccination regimen may be slightly better than prime-boost vaccine regimen and the mechanism of protection appears to be largely mediated by a Th2-biased response.

The use of complementary and alternative medicines for breast cancer patients has been increasing every year. Traditional Indian systems of medicine, such as Siddha, have been reported to benefit patients in India through herbal interventions for cancer. One such herbal medicine is Semecarpus Lehyam (SL), and this study aims at providing a scientific basis for the anti-tumor property of SL with respect to breast cancer. SL was subjected to serial extraction with four organic solvents of increasing polarity (n-hexane, chloroform, ethyl acetate, n-butanol and water). The solvents from all fractions were removed, dried and dissolved in dimethyl sulfoxide for testing their anti-tumor activity against two breast cancer cell lines, MCF-7 [estrogen receptor (ER)-positive] and MDA 231 (ER-negative) using cell viability and apoptosis assays. The most potent SL fractions were also combined with radiation and doxorubicin to determine the radio- and chemo-sensitizing effects of SL on these breast cancer cell lines. In terms of cytotoxicity as well as induction of apoptosis, the n-hexane and chloroform fractions of SL were more significantly active against MDA 231 cells than MCF-7 cells. The n-butanol fraction of SL showed some activity against MCF-7 cells. When combined with radiation or doxorubicin, the n-hexane and chloroform fractions enhanced the radio-sensitivity (11.8-fold) and chemo-sensitivity (6.5-fold) of MDA 231 cells. This study demonstrated SL to be a potent anti-tumor agent against the ER-negative breast cancer cell line. The study is also the first step in the scientific validation of SL for use against breast cancer, particularly the ER-negative type.

Purpose: The use of complementary and alternative medicine (CAM) in cancer has been increasing. The therapeutic modalities which originated from India, viz., Ayurveda and Siddha, have phytotherapy as their fundamental basis and, therefore, produce few side effects. They are among the most ancient medicinal systems and are still being practiced in India and elsewhere, to cure cancer and other diseases. Many Siddha practitioners in the southern parts of India prescribe rasagenthi lehyam (RL) as a drug for cancer. RL contains 38 different botanicals, many of which have been shown to possess therapeutic efficacy, and 8 inorganic compounds, all prepared into a paste in a palm sugar and hen's egg base. The efficacy of RL in killing prostate cancer cells in vitro was investigated in this study to determine whether RL could be recommended as a CAM for prostate cancer., Methods: In order to scientifically validate the anticancer activity of RL on prostate cancer, a methanolic extract of RL was serially extracted with four organic solvents, and the extracts were tested for clonogenic inhibition and induction of apoptosis in PC-3 prostate cancer cells, with and without irradiation. n-Hexane, ethyl acetate and chloroform extracts of RL effectively killed PC-3 cells., Results: The IC(50) values of n-hexane, ethyl acetate and chloroform extracts of RL were 3.84 microg/ml, 3.68 microg/ml and 75 ng/ml, respectively. All three extracts induced apoptosis in PC-3 cells. Further, all the three extracts when combined with radiation, caused enhanced effect on killing of PC-3 cells. Among the three extracts, the chloroform extract showed the most significant radiation-sensitizing effect., Conclusion: RL, either in its original formulation prepared under strict quality control or its chloroform extract, could potentially be an alternative medicine for prostate cancer, and also a sensitizing agent in the context of radiation therapy for prostate cancer, as a complementary medicine. A more directed study could lead to the identification of the active principle(s) in the chloroform extract of RL for use in prostate cancer therapy.

Prior studies have demonstrated that transglutaminase (TGase) from the human filarial parasite Brugia malayi is critical for the growth and development of the larval stages. In this report, we describe the cloning and partial characterization of a cDNA encoding the B. malayi TGase (BmTGase). Using RT-PCR and RACE-PCR, the cDNA was amplified from adult worm mRNA. BmTGase is 1,881 bp long and codes for a protein with a predicted molecular mass of 54 kDa. Amino acid sequence analysis of BmTGase revealed significant homology to the protein disulfide isomerase (PDI), particularly, to the PDI-related protein ERp60, a PDI isoform found in the lumen of endoplasmic reticulum. The activity of recombinant B. malayi TGase enzyme (rBmTG) was found to be calcium-dependent and could be inhibited by EDTA. ELISA studies showed that approximately 88% of 48 sera from healthy Indian patients living in a bancroftian filariasis endemic area were reactive with rBmTG. In contrast, only 33% of sera from patients with clinical filariasis were reactive to rBmTG. Non-endemic sera were uniformly non-reactive. Additional studies are needed to elucidate the role, if any, of B. malayi TGase in protective immunity to filariasis.

We have shown that the requirement of the epsilon-isoform of diacylglycerol kinase for diacylglycerols containing arachidonic acid is specific for this substrate and cannot be replaced by the presence of an arachidonoyl group in other places in the membrane; rather, it has to be present on the substrate itself. In addition, we demonstrate that the increased activity shown toward 1-stearoyl-2-arachidonoylglycerol by the epsilon-isoform of diacylglycerol kinase is not a consequence of altered membrane physical properties but is rather a specific interaction with the arachidonoyl group. We have also compared the modulation of the activity of the epsilon-isoform of diacylglycerol kinase with that of the zeta-isoform with regard to some of the intermediates involved in phosphatidylinositol cycling. One of the products of the hydrolysis of phosphatidylinositol diphosphate is diacylglycerol enriched in arachidonic acid. The activity of the epsilon-isoform is known to be specific for this form of diacylglycerol. We show that in contrast, the activity of the zeta-isoform is lower against 1-stearoyl-2-arachidonoylglycerol compared with dioleoylglycerol. We demonstrate that addition of phosphatidylserine, as well as other anionic phospholipids including L-alpha-phosphatidylinositol 4,5-bisphosphate, strongly inhibits the epsilon-isoform, but these anionic lipids increase the activity of the zeta-isoform. Addition of Ca(2+), which is released from internal stores as a consequence of phosphatidylinositol cycling, promotes the activity of the epsilon-isoform of this enzyme but has little effect on the zeta-isoform. The contrasting conditions required for maximal activity of these two isoforms of diacylglycerol kinase, as well as their different substrate specificity, suggest that they have different physiological roles in signal transduction.