Saponins as novel TNF-alpha inhibitors: isolation of saponins and a nor-pseudoguaianolide from Parthenium hysterophorus.

Two novel saponins and a 13-nor-pseudoguaianolide designated as hysterolactone were isolated from Parthenium hysterophorus. The two saponins were found to be potent inhibitors of TNF-alpha. Their mode of inhibition was studied through molecular modeling. The wet lab results were in concordance with the data obtained from docking experiments.

Structure-activity relationship (SAR) of parthenin analogues with pro-apoptotic activity: Development of novel anti-cancer leads.

Analogues of parthenin were synthesized by substitutions at different reaction centres to establish a structure-activity relationship (SAR). Some of the molecules have displayed significant cytotoxicity in human cervical carcinoma (HeLa) and human myeloid leukemia (HL-60) cells. A few of the compounds also induced apoptosis in HL-60 cells measured in terms of sub-Go/G1 DNA fraction. Also one of the lead molecules has been shown to be the inhibitor of both telomerase and topoisomerase-II.

The Singaporean English and Chinese versions of the EQ-5D achieved measurement equivalence in cancer patients.

OBJECTIVE: To assess measurement equivalence of the Singaporean English and Chinese versions of the EuroQol Group's 5-domain questionnaire (EQ-5D) in cancer patients. STUDY DESIGN AND SETTING: Seven hundred and seventy-one ethnic Chinese patients in Singapore were recruited, and they answered either an English or a Chinese version of the EQ-5D. Seven days later, a similar questionnaire in the same language was mailed to the patients. Regression analysis was used to assess equivalence of the mean values obtained by using the two language versions. The validity, responsiveness to change, and reliability of the two versions of the EQ-5D were assessed and compared. RESULTS: Based on the prespecified equivalence margin of +/-10% for binary outcome, +/-0.05 for utility index, and +/-5 points in the visual analog scale, the two language versions of the EQ-5D gave equivalent mean values at item and scale levels. They also showed similar characteristics in validity, responsiveness, and reliability. For example, the test-retest reliability values for the EQ-5D utility index in the two language samples were identical in two significant digits: 0.79. CONCLUSION: The Singaporean English and Chinese versions of the EQ-5D were validated in cancer patients and were shown to achieve measurement equivalence.

Mapping the English and Chinese versions of the Functional Assessment of Cancer Therapy-General to the EQ-5D utility index.

OBJECTIVE: This study aims to develop a function for mapping the English and Chinese versions of the Functional Assessment of Cancer Therapy-General (FACT-G) scores to the EuroQoL Group's EQ-5D utility index and to test whether a single function is sufficient for the two language versions. METHODS: A baseline survey of 558 cancer patients in Singapore using the FACT-G and EQ-5D was conducted (308 English and 250 Chinese questionnaires). Regression models were used to predict the EQ-5D utility index values based on the FACT-G scores and thus derive a mapping equation. Data from a follow-up survey of the patients were used to validate the results. RESULTS: The FACT-G Social/Family scale was not associated with the EQ-5D utility index (P = 0.701). There was no interaction between language version and the predictors (each P > 0.1). An equation that maps the FACT-G Physical, Emotional, and Functional well-being scales to the EQ-5D utility index was derived. In the validation sample, the mean observed utility values was larger than the mapped by only 0.005 (95% confidence interval [CI]-0.006 to 0.016), but the mean absolute difference was 0.083 (95% CI 0.076 to 0.090). CONCLUSIONS: At the group level, but not individual level, the equation developed can accurately map the English and Chinese versions of the FACT-G scores to the EQ-5D utility index.

A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells.

A triterpenediol (TPD) comprising of isomeric mixture of 3alpha, 24-dihydroxyurs-12-ene and 3alpha, 24-dihydroxyolean-12-ene from Boswellia serrata induces apoptosis in cancer cells. An attempt was made in this study to investigate the mechanism of cell death by TPD in human leukemia HL-60 cells. It inhibited cell proliferation with IC50 approximately 12 microg/ml and produced apoptosis as measured by various biological end points e.g. increased sub-G0 DNA fraction, DNA ladder formation, enhanced AnnexinV-FITC binding of the cells. Further, initial events involved massive reactive oxygen species (ROS) and nitric oxide (NO) formation, which were significantly inhibited by their respective inhibitors. Persistent high levels of NO and ROS caused Bcl-2 cleavage and translocation of Bax to mitochondria, which lead to loss of mitochondrial membrane potential (Deltapsim) and release of cytochrome c, AIF, Smac/DIABLO to the cytosol. These events were associated with decreased expression of survivin and ICAD with attendant activation of caspases leading to PARP cleavage. Furthermore, TPD up regulated the expression of cell death receptors DR4 and TNF-R1 level, leading to caspase-8 activation. These studies thus demonstrate that TPD produces oxidative stress in cancer cells that triggers self-demise by ROS and NO regulated activation of both the intrinsic and extrinsic signaling cascades.