Combinatorial Drug Therapy with Phytochemicals as Adjuvants in Prostate Cancer Management

Prostate cancer is one of the leading cancers in men needs a long period for development from small lesion to become a clinical manifestation. The prostate specific antigen is a prominent tumor marker for prostate cancer. Androgens are involved in the development and progression of prostate cancer regulating the androgen receptor as androgen-dependent or androgen-independent types. The latter occurs in metastatic conditions of prostate cancer developed as hormone resistant prostate cancer (HRPC) that inappropriately activates transcription of other genes involved in molecular pathways inducing cellular proliferation and inhibiting apoptosis. Since prostate cancer is characterized by slow growth and long latency period and thus integration of phytochemicals/compounds in combination with other existing therapies have promising future to manage cancer, thus controlling the disease progression and mortality rate. Therefore, the medicinal plants therapeutic or prophylactic activities on prostate cancer exhibiting anti-androgenic effects, depleting PSA, down-regulating expression of androgen receptor, regulating cell cycle regulators have promising future to be applied as adjuvant drugs in prostate cancer treatment

ANTI-CANCER POTENTIAL OF POLYSACCHARIDE ISOLATED FROM METHANOLIC EXTRACT OF TINOSPORA CORDIFOLIA STEM BARK

Objective: The exploration of the anticancer potential of polysaccharide isolated from the methanolic extract of Tinospora cordifolia (T. cordifolia) stem bark against breast cancer in DMBA-induced female albino Wistar rat models were examined by various hematological parameters. Methods: Analysis of Red blood cell (RBC), White blood cell (WBC) and platelet level, Tumor markers Carcino Embryonic Antigen (CEA) and Cancer Antigen 15.3 (CA 15.3) in the serum, was done in the normal, cancer and compound treated rats using specific kits. Histological studies were performed to examine the changes in the tissue morphology and cell patterns in breast tissue. Results: The decreased levels of RBC, WBC and platelets in 7,12-Dimethylbenz [a] anthracene (DMBA)-induced breast cancer (Group III) animals were revived to the normal conditions in polysaccharide treated breast cancer (Group IV) animals as that of normal (Group I). The level of tumor markers CEA and CA 15.3, was found elevated in serum of DMBA-induced breast cancer groups (Group III) when compared to their levels in the normal groups (Group I) whereas polysaccharide treatment (Group IV) prevented this rise in the levels of tumor markers. The histological studies on the breast tissue samples of all the groups showed the appropriate features where the normal (Group I) animals were characterized with normal cells uniformly arranged without any change in orientation and morphology, DMBA-induced cancer (Group III) animals showed an improper orientation of cells arranged as glandular structures, as nest, or cords of various sizes or as solid sheets foci of necrosis in some areas with margins infiltrating, pushing, circumcised or mixed and the polysaccharide treated (Group IV) animals showed results resembling that of the normal (Group I) animals. Conclusion: Thus, polysaccharide is proved as an effective chemo preventive agent against breast cancer

Novel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats

Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from Cassia fistula stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (p p p p p p p p p p p p p p p p Tyr612 (p p Ser473 (p p p < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1–C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1–C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes

IN VITRO AND IN SILICO STUDIES ON EVALUATING EREMANTHIN AS POTENTIAL THERAPEUTIC DRUG AGAINST BREAST CANCER

Objective: The present study was aimed to evaluate the anticancer property of eremanthin isolated from Costus speciosus against breast cancer using in vitro and in silico approaches and thereby to develop eremanthin as a typical phytotherapeutic drug against cancer. Methods: The presence of specific biologically active extract was confirmed under GC–MS/MS (gas chromatography–mass spectrometry) analysis. The cell proliferation inhibitory effect of the eremanthin was confirmed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and LDH (lactate dehydrogenase) assay. In silico studies were performed to predict the targeted interaction of eremanthin with cancer proteins. Results: The GC–MS/MS analysis confirmed the presence of eremanthin with peak value of RA: 20.03. The MTT and LDH assays revealed the antiproliferative activity of eremanthin on MCF-7 and MDA-MB-231 breast cancer cell lines. The results provide stable interaction between eremanthin and cancer target proteins. Conclusion: Thus, the compound can be used as an effective herbal therapeutic molecule to treat cancer with further explorations

Acute Free-Iron Exposure Does Not Explain the Impaired Haemorheology Associated with Haemochromatosis.

Given the severity of the current imbalance between blood donor supply and recipient demand, discarded blood drawn from the routine venesections of haemochromatosis (HFE-HH) patients may serve as a valuable alternative source for blood banks and transfusion. We investigated whether functional or biochemical differences existed between HFE-HH and control blood samples, with particular focus upon the haemorheological properties, to investigate the viability of venesected blood being subsequently harvested for blood products.Blood samples were collected from HFE-HH patients undergoing venesection treatment (n = 19) and healthy volunteers (n = 8). Moreover, a second experiment investigated the effects of a dose-response of iron (0, 40, 80, 320 mM FeCl3) on haemorheology in healthy blood samples (n = 7). Dependent variables included basic haematology, iron status, haematocrit, red blood cell (RBC) aggregation (native and standardised haematocrit) and "aggregability" (RBC tendency to aggregate in a standard aggregating medium; 0.4 L/L haematocrit in a Dx70), and RBC deformability.Indices of RBC deformability were significantly decreased for HFE-HH when compared with healthy controls: RBC deformability was significantly decreased at 1-7 Pa (p < 0.05), and the shear stress required for half maximal deformability was significantly increased (p < 0.05) for HFE-HH. RBC aggregation in plasma was significantly increased (p < 0.001) for HFE-HH, although when RBC were suspended in plasma-free Dx70 no differences were detected. No differences in RBC deformability or RBC aggregation/aggregability were detected when healthy RBC were incubated with varying dose of FeCl3.HFE-HH impairs the haemorheological properties of blood; however, RBC aggregability was similar between HFE-HH and controls when cells were suspended in a plasma-free medium, indicating that plasma factor(s) may explain the altered haemorheology in HFE-HH patients. Acute exposure to elevated iron levels does not appear (in isolation) to account for these differences. Further consideration is required prior to utilising routine venesection blood for harvesting RBC concentrates due to the potential risk of microvascular disorders arising from impaired haemorheology

Aggregation of RBC suspensions in autologous plasma following incubation with various concentration of FeCl₃.

<p>Incubation with FeCl₃ did not influence the RBC aggregation at stasis (M₀; Panel A) or at low-shear (M₁; Panel B).</p

Red cell aggregation for haemochromatosis (HFE-HH) patients and healthy controls (Con) measured in plasma suspensions at native and a standardised (0.4 L/L) haematocrit, and red cell aggregability in a standard aggregating medium (Dx70).

<p>Red cell aggregation was increased for HFE-HH when compared with Con while at stasis (“M₀”; Panel A) at native and standardised haematocrit. The same observation was made for aggregation measures at low-shear (“M₁”; Panel B). Red cell aggregability was not different between groups at stasis or low-shear. ***, HFE-HH significantly increased compared with Con, p < 0.001.</p

The Elongation Index (EI) of RBC in autologous plasma at varying shear stresses (Panel A) following an incubation with varying concentration of FeCl₃ (0, 40, 80, 320 uM).

<p>The varied iron incubated conditions did not influence the maximal EI (EI_max; Panel B) or the amount of shear stress required for half maximal EI (SS_half; Panel C).</p

Red cell deformability (Elongation Index; Panel A) was decreased at discrete shear stresses for haemochromatosis (HFE-HH) when compared with healthy controls (CON).

<p>Maximal Elongation Index (EI_max) was not different between groups (Panel B); however, the shear stress required for half-maximal elongation index (SS_1/2) was significantly increased for HFE-HH (Panel C). *, p < 0.05. **, p < 0.01.</p