PATIENTS AND METHODS: A total of 120 men, aged 40-70 years, with TD (serum total testosterone [TT] ≤ 12 nmol/L) were randomised to receive either i.m. TU (1000 mg) or placebo. In all, 58 and 56 men in the placebo and treatment arm, respectively, completed the study. Participants were seen six times in the 48-week period and the following data were collected: physical examination results, haemoglobin, haematocrit, TT, lipid profile, fasting blood glucose, sex hormone-binding globulin, liver function test, prostate- specific antigen (PSA) and adverse events.
RESULTS: The mean (sd) age of the participants was 53.4 (7.6) years. A significant increase in serum TT (P < 0.001), PSA (P = 0.010), haematocrit (P < 0.001), haemoglobin (P < 0.001) and total bilirubin (P = 0.001) were seen in the treatment arm over the 48-week period. Two men in the placebo arm and one man in the treatment arm developed myocardial infarction. Common adverse events observed in the treatment arm included itching/swelling/pain at the site of injection, flushing and acne. Overall, TU injections were well tolerated.
CONCLUSIONS: TU significantly increases serum testosterone in men with TD. PSA, haemoglobin and haematocrit were significantly elevated but were within clinically safe limits. There was no significant adverse reaction that led to the cessation of treatment.
Methods: This study investigated the cytotoxic effect of the venom from Trimeresurus purpureomaculatus, the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue.
Results: The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC50) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C18 reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study.
Conclusion: Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian T. purpureomaculatus venom and suggested its anticancer potential in drug discovery.
Methods: The cytotoxicity of the Ligno TG-K against human breast (MCF7), prostate (PC3) and lung (A549) adenocarcinoma cell lines was evaluated using MTT cytotoxicity assay. The cytotoxic mechanisms of the active high molecular weight proteins (HMWp) fraction were investigated through detection of caspases activity and apoptotic-related proteins expression by Western blotting. The in vivo antitumor activity of the isolated HMWp was examined using MCF7 mouse xenograft model. Shotgun LC-MS/MS analysis was performed to identify the proteins in the HMWp.
Results and Discussion: Cold water extract of the sclerotia inhibited proliferation of MCF7, A549 and PC3 cells with IC50 ranged from 28.9 to 95.0 µg/mL. Bioassay guided fractionation of the extract revealed that HMWp exhibited selective cytotoxicity against MCF7 cells via induction of cellular apoptosis by the activation of extrinsic and intrinsic signaling pathways. HMWp activated expression of caspase-8 and -9 enzymes, and pro-apoptotic Bax protein whilst inhibiting expression of tumor survivor protein, Bcl-2. HMWp induced tumor-cell apoptosis and suppressed growth of tumor in MCF-7 xenograft mice. Lectins, serine proteases, RNase Gf29 and a 230NA deoxyribonuclease are the major cytotoxic proteins that accounted for 55.93% of the HMWp.
Conclusion: The findings from this study provided scientific evidences to support the traditional use of the L. tigris sclerotia for treatment of breast cancer. Several cytotoxic proteins with high abundance have been identified in the HMWp of the sclerotial extract and these proteins have potential to be developed into new anticancer agents or as adjunct cancer therapy.
OBJECTIVE: The objective of this study is to evaluate the anti-cancer potential of the novel class of quinazoline tethered acetamide derivatives against six different cancer cell lines.
METHOD: A novel series of various substituted quinazolinone acetamides were synthesized through a feasible scheme. The synthetic scheme involves the conversion of benzoxazinone (from anthranilic acid and benzoyl chloride) intermediate to 3-amino quinazoline-4-one which is further converted to the final amide by tethering with the propionyl chloride employing Schotten-Baumann Reaction conditions. All the synthesized derivatives characterized by IR, 1HNMR and MASS spectral methods and anti-cancer activity evaluated by employing MTT assay for six cancer cell lines and one normal human cell line.
RESULTS: All the synthesized compounds were screened for anti-cancer activity against six cancer cell lines, including A 549 (lung), DU 145 (prostate), HT 29 (colon), MCF-7 (breast), SiHA (cervical), B16F10 (mouse skin melanoma) and one normal human fibroblast cell lines. All the compounds displayed a decent cytotoxicity profile when compared with the standard drug, doxorubicin. Among the synthesized compounds (5a to 5n) tested, two compounds, 5f and 5g have demonstrated excellent cytotoxicity against SiHA and MCF-7 cancer cell lines.
CONCLUSION: Comparatively, most of the compounds displayed decent cytotoxicity potential relative to the standard drug, doxorubicin. Further investigations are needed to establish the detailed mechanism of action of the developed novel quinazolinone acetamides.