Facets of rhizospheric microflora in biocontrol of phytopathogen Macrophomina phaseolina in oil crop soybean.

The use of microbial bioinoculants for managing plant diseases and promoting plant growth is an effective alternative approach to integrated farming. One of the devastating phytopathogens is Macrophomina phaseolina (Tassi) Goid. It is an omnipresent fungus infecting more than 500 plant species. It causes charcoal rot disease in soybean leading to 30-50% yield loss. Soybean Glycine max (L.) oil seed crop produced globally is highly susceptible to M. phaseolina. India is the fifth largest producer of soybean in the world. Madhya Pradesh is the largest soybean-producing state in India; Around 70% yield loss of soybean is accounted to M. phaseolina infection in India. Control of charcoal rot is the requisite of the current situation. Chemical control is not feasible due to saprophytic nature and prolonged survival of Macrophomina phaseolina. Chemical fungicides are expensive, toxic, hazardous, and cause pollution. Biological control is an effective approach to control this devastating fungus. The rhizosphere of soil is rich in beneficial microflora competent to suppress plant pathogens and also promote plant growth. PGPR have well-developed mechanisms that impart antagonistic traits to them. PGPR produces various antifungal metabolites siderophores and HCN which inhibit fungal growth, and can be used as potent BCA. Pseudomonas and Bacillus species have been reported effective against M. phaseolina. The mechanisms and antifungal compounds produced by these bacteria to control charcoal rot can be studied extensively. BCA or the metabolites secreted by them have the potential to develop effective bioformulations for soybean at the commercial level for sustainable agriculture.

Nitrogen alleviates salinity toxicity in Solanum lycopersicum seedlings by regulating ROS homeostasis.

The present study was aimed to investigate adaptation in physiology and biochemistry of Solanum lycopersicum seedlings under NaCl (NaCl0; 0.0 g NaCl kg-1 sand, NaCl1; 0.3 g NaCl/kg sand and NaCl2; 0.5 g NaCl/kg sand) stress, simultaneously supplemented with different (deprived; 0 mg/kg sand, LN; 105 mg/kg sand, MN; 210 mg/kg sand and HN; 270 mg/kg sand) levels of nitrogen (N). NaCl at both doses caused significant loss in growth, K+ content, K+/Na+ ratio, total chlorophyll and photosynthetic oxygen evolution. Further, N supplementation influences growth of test seedlings, that attained maximum growth in HN followed by MN, LN and deprived N conditions. N at HN level significantly declined Na+ accumulation in the cell and enhanced level of K+. NaCl treatment enhanced level of oxidative stress biomarkers: superoxide radical (O2•-), hydrogen peroxide (H2O2), MDA equivalents contents and electrolyte leakage in leaf as well as root despite enhanced activity of SOD, POD, CAT and GST, and enzymes participating in the ascorbate-glutathione cycle (AsA-GSH cycle) viz. APX, DHAR and GR. At the same time, higher contents of total AsA (AsA + DHA) and total GSH (GSH + GSSG), and maintained ratios of AsA/DHA and GSH/GSSG in HN fed seedlings were observed. Overall, the results suggest that HN supplementation was able in alleviating NaCl induced toxicity in test seedlings which was mainly due to the up-regulation of the AsA-GSH cycle, K+ and K+/Na+ ratio, which resulted into better growth performance of HN fed seedlings under NaCl stress while reverse was noticed for LN and deprive N conditions.

Responses of photosynthesis, nitrogen and proline metabolism to salinity stress in Solanum lycopersicum under different levels of nitrogen supplementation.

In the present study, effect of different levels of nitrogen (N0, deprived; N25, sub-optimum; N75, optimum and N150, supra-optimum) in Solanum lycopersicum L. seedlings under NaCl (NaCl1, 0.3 g kg-1 sand and NaCl2, 0.5 g kg-1sand) stress was investigated. Biomass accumulation, pigments, K+ concentration, nitrate and nitrite contents were declined by NaCl in dose dependent manner. As compared to control (N75 without NaCl), fresh weight declined by 4% and 11%, and dry weight by 7 and 13% when seedlings were grown under N75+NaCl1 and N75+NaCl2 combinations, respectively. Furthermore, fluorescence parameters (JIP-test): the size and number of active reaction centres of photosynthetic apparatus (Fv/F0), efficiency of water splitting complex (F0/Fv), quantum yield of primary photochemistry (φP0 or Phi_P0), yield of electron transport per trapped excitation (Ψ0 or Psi_0), the quantum yield of electron transport (φE0), and performance index of PS II (PIABS) and parameters related to energy fluxes per reaction centre (ABS/RC, TR0/RC, ET0/RC and DI0/RC) were also affected by NaCl. However, toxic effect of NaCl on photosystem II photochemistry was ameliorated by N. The lower dose (NaCl1) of NaCl exerts damaging effect on oxidation side of PS II, while higher dose (NaCl2) damages PS II reaction centre and its reduction side. Moreover, control seedlings (N75 without NaCl) when exposed to NaCl1 and NaCl2 exhibited a significant enhancement in respiration rate by 6 and 16%, Na+ accumulation by 111 and 169% in shoot, and 141 and 223% in root and ammonium contents by 19 and 34% respectively. Nitrate and ammonium assimilating enzymes such as nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS) and glutamate synthase (GOGAT) were adversely affected by NaCl stress while glutamate dehydrogenase (GDH) showed reverse trend. N addition caused further enhancement in free proline, and activity of Δ1-pyrroline-5-carboxylate synthetase (P5CS), while activity of proline dehydrogenase (ProDH) decreased. The results indicate that different levels of N significantly modulated NaCl-induced damaging effects in tomato seedlings. Furthermore, the results suggest that after N addition Na+, nitrite, nitrate, ammonium contents, nitrogen metabolic enzymes, proline content, and activity of P5CS are favourably regulated, which might be associated with mitigation of NaCl stress and effect was more pronounced with supra-optimum level of N (N150).

PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma.

The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich's ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG.

Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage.

In spite of proficient results of several phytochemicals in preclinical settings, the conversion rate from bench to bedside is not very encouraging. Many reasons are attributed to this limited success, including inefficient systemic delivery and bioavailability under in vivo conditions. To achieve improved efficacy, polyphenolic constituents of black (theaflavin [TF]) and green (epigallocatechin-3-gallate [EGCG]) tea in poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) were entrapped with entrapment efficacy of ~18% and 26%, respectively. Further, their preventive potential against 7,12-dimethylbenzanthracene (DMBA)-induced DNA damage in mouse skin using DNA alkaline unwinding assay was evaluated. Pretreatment (topically) of mouse skin with either TF or EGCG (100 µg/mouse) doses exhibits protection of 45.34% and 28.32%, respectively, against DMBA-induced DNA damage. However, pretreatment with TF-loaded PLGA-NPs protects against DNA damage 64.41% by 1/20th dose of bulk, 71.79% by 1/10th dose of bulk, and 72.46% by 1/5th dose of bulk. Similarly, 51.28% (1/20th of bulk), 57.63% (1/10th of bulk), and 63.14% (1/5th of bulk) prevention was noted using EGCG-loaded PLGA-NP doses. These results showed that tea polyphenol-loaded PLGA-NPs have ~30-fold dose-advantage than bulk TF or EGCG doses. Additionally, TF- or EGCG-loaded PLGA-NPs showed significant potential for induction of DNA repair genes (XRCC1, XRCC3, and ERCC3) and suppression of DNA damage responsive genes (p53, p21, MDM2, GADD45α, and COX-2) as compared with respective bulk TF or EGCG doses. Taken together, TF- or EGCG-loaded PLGA-NPs showed a superior ability to prevent DMBA-induced DNA damage at much lower concentrations, thus opening a new dimension in chemoprevention research.

RETRACTED: Tea polyphenols enhance cisplatin chemosensitivity in cervical cancer cells via induction of apoptosis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Multiple figures in this article appear to be falsified/fabricated. Figure 2A and C. The representative dot plots from the EGCG (15ug/ml)+CDDP (10ug/ml) and TF (15ug/ml) groups appear to be duplicated. Figures 3, 4 and 6. Multiple Western blot bands appear to be rotated and reused throughout Figure 3 (A and B); 4 (A and B) and 6 (A, B, C). In particular, the Cytochrome-c blot in Figure 3B is duplicated and flipped in Figure 6B as p-NFKB. The p53 blot in Figure 3B is duplicated in Figure 6C as p-NFKB. The B-actin blot in Figure 3B is shown as an unmarked control lane (flipped in Figure 6B. The p53 band in Figure 3C is very similar to the Caspase 9 blot in Figure 4B and is cropped and duplicated in Figure 6A as p-NFKB by cisplatin in SiHa cells. The Caspase 3 blot in Figure 4A is rotated and flipped and appears in Figure 6B as p-IKBa.

Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G(2)/M arrest to apoptosis.

Bromelain, obtained from pineapple, is already in use clinically as adjunct in chemotherapy. Our objective was to test its ability to act as a sole anti-cancer agent. Therefore, we describe its anti-proliferative, anti-inflammatory and subsequent anti-cancer effects in vitro, against human epidermoid carcinoma-A431 and melanoma-A375 cells. Bromelain exhibited reduction in proliferation of both these cell-lines and suppressed their potential for anchorage-independent growth. Further, suppression of inflammatory signaling by bromelain was evident by inhibition of Akt regulated-nuclear factor-kappaB activation via suppression of inhibitory-kappaBα phosphorylation and concomitant reduction in cyclooxygenase-2. Since, the inflammatory cascade is well-known to be closely allied to cancer; we studied the effect of bromelain on events/molecules central to it. Bromelain caused depletion of intracellular glutathione and generation of reactive oxygen-species followed by mitochondrial membrane depolarization. This led to bromelain-induced cell-cycle arrest at G(2)/M phase which was mediated by modulation of cyclin B1, phospho-cdc25C, Plk1, phospho-cdc2, and myt1. This was subsequently followed by induction of apoptosis, indicated by membrane-blebbing, modulation of Bax-Bcl-2 ratio, Apaf-1, caspase-9, and caspase-3; chromatin-condensation, increase in caspase-activity and DNA-fragmentation. Bromelain afforded substantial anti-cancer potential in these settings; hence we suggest it as a potential prospect for anti-cancer agent besides only an additive in chemotherapy.

Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53.

Cancer chemoprevention by natural dietary agents has received considerable importance because of their cost-effectiveness and wide safety margin. However, single agent intervention has failed to bring the expected outcome in clinical trials; therefore, combinations of chemopreventive agents are gaining increasing popularity. The present study aims to evaluate the combinatorial chemopreventive effects of resveratrol and black tea polyphenol (BTP) in suppressing two-stage mouse skin carcinogenesis induced by DMBA and TPA. Resveratrol/BTP alone treatment decreased tumor incidence by ∼67% and ∼75%, while combination of both at low doses synergistically decreased tumor incidence even more significantly by ∼89% (p<0.01). This combination also significantly regressed tumor volume and number (p<0.01). Mechanistic studies revealed that this combinatorial inhibition was associated with decreased expression of phosphorylated mitogen-activated protein kinase family proteins: extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase 1/2, p38 and increased in total p53 and phospho p53 (Ser 15) in skin tissue/tumor. Treatment with combinations of resveratrol and BTP also decreased expression of proliferating cell nuclear antigen in mouse skin tissues/tumors than their solitary treatments as determined by immunohistochemistry. In addition, histological and cell death analysis also confirmed that resveratrol and BTP treatment together inhibits cellular proliferation and markedly induces apoptosis. Taken together, our results for the first time lucidly illustrate that resveratrol and BTP in combination impart better suppressive activity than either of these agents alone and accentuate that development of novel combination therapies/chemoprevention using dietary agents will be more beneficial against cancer. This promising combination should be examined in therapeutic trials of skin and possibly other cancers.

Tea polyphenols induce apoptosis through mitochondrial pathway and by inhibiting nuclear factor-kappaB and Akt activation in human cervical cancer cells.

Phytochemicals present in tea, particularly polyphenols, have anticancer properties against several cancer types. However, studies elucidating the role and the mechanism(s) of action of tea polyphenols in cervical cancer are sparse. In this study, we investigated the mechanism of antiproliferative and apoptotic actions exerted by tea polyphenols on human papilloma virus-18-positive HeLa cervical cancer cells. Treatment of green tea polyphenol (-)-epigallocatechin gallate (EGCG) and black tea polyphenol theaflavins (TF) in HeLa cells showed a marked concentration- and time-dependent inhibition of proliferation and induced sub-G1 phase in a dose-dependent manner after 24 h. There was an attenuation of mitochondrial membrane potential with the increase of reactive oxygen species generation, p53 expression, Bax/Bcl-2 ratio, cytochrome-c release, and cleavage of procaspase-3 and -9 and poly(ADP-ribose)-polymerase, indicating the participation of a mitochondria related mechanism. In addition, EGCG as well as TF inhibited activation of Akt and nuclear factor-kappaB (NF-kappaB) via blocking phosphorylation and subsequent degradation of inhibitor of kappaBalpha and kappaBbeta subunits, thereby downregulating cyclooxygenase-2. Additionally, the protein level of cyclin D1, a transcriptional target of NF-kappaB, was also reduced significantly. Thus, we can conclude that tea polyphenols inhibit the growth of cervical cancer cells by inducing apoptosis and regulating NF-kappaB and Akt.

Enhancement of cancer chemosensitization potential of cisplatin by tea polyphenols poly(lactide-co-glycolide) nanoparticles.

Anti-cancer potential of polymer based nanoparticle of EGCG and TF alone and in combination with anti-cancer drug cisplatin have been studied in human cancer lines: A549 (lung carcinoma), HeLa (cervical carcinoma) and THP-1 (acute monocytic leukemia) using cell proliferation assay and cell cycle analysis. Encapsulated polyphenols retained biological effectiveness with over 20-fold dose advantage than EGCG/TF in exerting anti-cancer effects and also enhanced the potential of a widely used anti-cancer drug cisplatin. Subsequently, encapsulated polyphenols alone or in combination with cisplatin were more effective in inhibiting cell proliferation, metastasis, angiogenesis and apoptosis biomarkers. Collectively, our observations reveal that nanoparticle-mediated delivery of phytochemicals could serve as a basis for enhancing bioavailability and limiting the unwanted toxicity of chemotherapeutic agents.

Synergistic growth inhibition of mouse skin tumors by pomegranate fruit extract and diallyl sulfide: evidence for inhibition of activated MAPKs/NF-κB and reduced cell proliferation.

Limited outcomes from earlier chemopreventive studies have necessitated that some modifications be made to get better efficacy. It is proposed that cancer prevention is more feasible than treatment, and this could be achieved effortlessly with use of multiple agents competent of targeting multiple targets. This study was initiated to examine the chemopreventive efficacy of pomegranate fruit extract (PFE) and diallyl sulfide (DAS), alone and in combination, using 2-stage mouse skin tumorigenesis model. PFE and DAS alone delayed onset and tumor incidence by ∼55% and ∼45%, respectively, while their combination at low doses synergistically decreased tumor incidence more potentially (∼84%, p<0.01). In addition, regression in tumor volume was seen with continuous combinatorial treatment (p<0.01). Mechanistic studies revealed that this inhibition was associated with decreased expression of phosphorylated ERK1/2, JNK1 and activated NF-κB/p65, IKKα, IκBα phosphorylation and degradation in skin tissue/tumor. Histological and cell death analysis also confirmed that combined PFE and DAS inhibit cellular proliferation and markedly induce apoptosis than the single agents. Altogether, our results suggest that PFE and DAS in combination impart better suppressive activity than either of these agents alone and provide support that development of novel combination therapies/chemoprevention using dietary agents will be more beneficial against cancer.

Genotoxic and carcinogenic risks associated with the consumption of repeatedly boiled sunflower oil.

Repeated boiling of vegetable oils at high temperature in cooking and frying is a very common practice and leads to the formation of a class of toxic substances. Among them, polycyclic aromatic hydrocarbons (PAHs) are well-documented for their mutagenic/carcinogenic potential. The objectives of the present study were to evaluate the genotoxic and carcinogenic risks associated with the consumption of repeatedly boiled sunflower oil, which is one of the commonly consumed vegetable oils in southeast Asian countries. The presence of PAHs was analyzed using high-performance liquid chromatography (HPLC) methods in fresh, single-boiled, and repeatedly-boiled sunflower oil (FSO, SBSO, and RBSO) samples. A higher amount of known carcinogenic/mutagenic PAHs in RBSO samples were shown, as compared to FSO and SBSO. Oral administration of RBSO in Wistar rats resulted in significant induction of aberrant cells (p < 0.05) and micronuclei (p < 0.05) incidence in a dose-dependent manner. Oxidative stress analysis also showed a significant decrease in levels of antioxidant enzymes, such as superoxide dismutase and catalase, with a concurrent increase in reactive oxygen species and lipid peroxidation in animals following RBSO consumption, as compared to FSO or SBSO (p < 0.05). Additionally, RBSO administration alone and along with diethylnitrosamine for 12 weeks induced altered hepatic foci, as noticed by the alteration in positive (γ-glutamyl transpeptidase and glutathione-S-transferase) and negative (adenosine-triphosphatase, alkaline phosphatase, and glucose-6-phosphatase) liver biomarkers. A significant decrease in the relative and absolute hepatic weight in RBSO-supplemented rats was also noted (p < 0.05).

Genotoxic and carcinogenic risks associated with the dietary consumption of repeatedly heated coconut oil.

Repeated heating of vegetable oils at high temperatures during cooking is a very common cooking practice. Repeated heating of edible oils can generate a number of compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have been reported to have carcinogenic potential. Consumption of these repeatedly heated oils can pose a serious health hazard. The objectives of the present study were to evaluate the genotoxic and carcinogenic risks associated with the consumption of repeatedly heated coconut oil (RCO), which is one of the commonly consumed cooking and frying medium. The PAH were analysed using HPLC in fresh CO, single-heated CO (SCO) and RCO. Results revealed the presence of certain PAH, known to possess carcinogenic potential, in RCO when compared with SCO. Oral intake of RCO in Wistar rats resulted in a significant induction of aberrant cells (P<0·05) and micronuclei (P<0·05) in a dose-dependent manner. Oxidative stress analysis showed a significant (P<0·05) decrease in the levels of antioxidant enzymes such as superoxide dismutase and catalase with a concurrent increase in reactive oxygen species and lipid peroxidation in the liver. In addition, RCO given alone and along with diethylnitrosamine for 12 weeks induced altered hepatic foci as noticed by alteration in positive (γ-glutamyl transpeptidase and glutathione-S-transferase) and negative (adenosine triphosphatase, alkaline phosphatase and glucose-6-phosphatase) hepatospecific biomarkers. A significant decrease in the relative and absolute hepatic weight of RCO-supplemented rats was recorded (P<0·05). In conclusion, dietary consumption of RCO can cause a genotoxic and preneoplastic change in the liver.

Inhibition of hyaluronidase activity of human and rat spermatozoa in vitro and antispermatogenic activity in rats in vivo by Terminalia chebula, a flavonoid rich plant.

Our interest in development of hyaluronidase inhibitors as male antifertility agents led to identification of Terminalia chebula (T. chebula) plant with hyaluronidase (HAase) inhibitory activity of human spermatozoa ( approximately 93% inhibition) and rat caudal epididymal spermatozoa ( approximately 86% inhibition) in vitro at 30 mg/ml. We further demonstrated inhibition of hyaluronidase activity of testis and epididymal spermatozoa in vivo coincident with antispermatogenic activity and contraceptive efficacy of TC extract administered at 50 and 100mg/kg/day orally for 60 days in male albino rats. The significant decrease in motility, count and increase in morphological abnormalities of epididymal spermatozoa and severe reduction in fertility (-100%) of male rats treated with T. chebula fruit extract at 100mg/kg dose could be attributed to either direct effect on testis or direct or indirect interference with sperm maturation in epididymis, and/or inhibition of testicular and epididymal sperm hyaluronidase enzyme in vivo probably caused by flavonoids like tannins present in T. chebula.

Tea polyphenols inhibit cyclooxygenase-2 expression and block activation of nuclear factor-kappa B and Akt in diethylnitrosoamine induced lung tumors in Swiss mice.

BACKGROUND: Due to lack of validated screening methods and hence poor prognosis, treatment of lung cancer has not still improved up to the expectations. Therefore, risk of lung cancer needs to be minimized by efficient preventive measures. Tea (Camellia sinensis) and its bioactive polyphenols have been associated with prevention of human cancer for several organs. Thus, intake of tea polyphenols seems to be a viable mean to control lung cancer burden. In the present study, we studied the chemopreventive effects of green tea polyphenols (GTP) and black tea polyphenols (BTP) against diethylnitrosoamine (DEN) induced lung tumors in Swiss albino mice. RESULTS: Chemopreventive potential of tea polyphenols, was recorded as evident by, low incidence of alveologenic tumors in lungs of animals at tested doses (0.1% and 0.2% of both GTP and BTP) when compared with DEN (20 mg/kg b wt) treated animals. As a mechanism of cancer chemoprevention cellular signaling pathways were also targeted. GTP and BTP treatment inhibited the expression of Akt, cyclooxygenase-2 and inactivated nuclear factor-kappa B via blocking phosphorylation and subsequent degradation of IkappaB alpha. CONCLUSION: Thus, the study suggests that polyphenolic constituents of both cultivars of tea, i.e. green and black, have chemopreventive effects in DEN induced lung tumorigenesis in Swiss albino mice.

Regulation of cell growth through cell cycle arrest and apoptosis in HPV 16 positive human cervical cancer cells by tea polyphenols.

Cervical cancer is the second most common malignant neoplasm in women, in terms of both incidence and mortality rates worldwide. The polyphenolic constituents of tea (Camellia sinensis) have gained considerable attention because of its anti-cancer properties against a variety of cancers. Here we studied the effects of green and black tea polyphenols (GTP and BTP), on cellular proliferation and cell death in the SiHa cells (human cervical cancer) expressing the human papilloma virus (HPV)-16. The result showed that both GTP and BTP inhibited proliferation of cells in dose and time dependent manner. Cell cycle analysis showed anti-proliferative effect of GTP which is associated with an increase in the G2/M phase and apoptotic effect of BTP in 24 h treated SiHa cells. Further, on increase of incubation time for 48 h, GTP caused induction of apoptosis up to 20% of SiHa cells. The role GTP and BTP in apoptosis was further confirmed by reduction in mitochondrial membrane potential and increased levels of membrane phosphatidylserine. Thus, our data suggests that tea polyphenols exhibit anti-cancer potential against cervical cancer by inhibition of cell growth and induction of apoptosis.

Inhibitory effect of tea polyphenols on hepatic preneoplastic foci in Wistar rats.

Tea (Camellia sinensis) is one of the most widely used beverages worldwide and tea consumption has been shown to have an inverse correlation to the incidence of human cancers in epidemiological and experimental studies. In the present study, the protective effects of green tea polyphenols (GTP) and black tea polyphenols (BTP) in Wistar rats were assessed by medium-term bioassay, using altered hepatic foci (AHF) as end point. Animals were exposed to a single dose of diethylnitrosamine (DEN; 200 mg/kg body weight intraperitoneally), and GTP (1%) and BTP (1%) were then administered orally together with 0.05% 2-acetyl aminofluorene (2-AAF) crushed and mixed in the diet for 8 weeks. Numbers of AHF were scored and analyzed by quantitative stereology using the Image analysis system from frozen liver tissue sections. Tea polyphenol supplementation resulted in a significant protection against AHF induction in Wistar rats. In addition, levels of the positive biomarkers: gamma-glutamyl transpeptidase and glutathione-S-transferase (placental form) were reduced with GTP and BTP supplementation. Levels of the negative biomarkers adenosine triphosphatase and glucose-6-phosphatase were also restored by GTP and BTP administration. Thus, these results show the hepatoprotective effects of GTP and BTP against DEN- and 2-AAF-induced AHF development.

Protective effects of lupeol and mango extract against androgen induced oxidative stress in Swiss albino mice.

AIM: To investigate antioxidant potential of lupeol/mango pulp extract (MPE) in testosterone induced oxidative stress in prostate of male Swiss albino mice. METHODS: Oral treatment of lupeol (1 mg/animal) and MPE (1 mL [20% w/v]/animal) was given separately to animals along with subcutaneous injection of testosterone (5 mg/kg body weight) consecutively for 15 days. At the end of the study period, the prostate was dissected out for the determination of reactive oxygen species (ROS) levels, lipid peroxidation and antioxidant enzymes status (catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase). RESULTS: In testosterone treated animals, increased ROS resulted in depletion of antioxidant enzymes and increase in lipid peroxidation in mouse prostate. However, lupeol/MPE treatment resulted in a decrease in ROS levels with restoration in the levels of lipid peroxidation and antioxidant enzymes. CONCLUSION: The results of the present study demonstrate that lupeol/MPE are effective in combating oxidative stress-induced cellular injury of mouse prostate. Mango and its constituents, therefore, deserve study as a potential chemopreventive agent against prostate cancer.

In vitro and in vivo modulation of testosterone mediated alterations in apoptosis related proteins by [6]-gingerol.

Ginger (Zingiber officinale, Zingiberaceae) has been widely used as a dietary spice, and as a traditional oriental medicine. The rhizome of ginger contains pungent vanillyl ketones, including [6]-gingerol and [6]-paradol, and have been credited with therapeutic and preventive health benefits, including anti-cancer activity. Prostate cancer is an attractive target for chemoprevention because of its ubiquity, treatment-related morbidity, long latency between premalignant lesions and clinically evident cancer, and defined molecular pathogenesis. Here we are reporting the modulatory effects of [6]-gingerol on testosterone-induced alterations on apoptosis related proteins in both in vitro, androgen sensitive LNCaP cells and in vivo, ventral prostate of Swiss albino mice. [6]-gingerol treatment resulted apoptosis in LNCaP cells, as indicated by depolarization of mitochondrial membrane potential, increase in sub G1 cell population by flow cytometry and the appearance of DNA laddering pattern in agarose gel electrophoresis. Results of western blot analysis showed that [6]-gingerol upregulated the testosterone depleted levels of p53 in mouse prostate and upregulated its downstream regulator Bax and further activated Caspase-9 and Caspase-3 in both LNCaP cells and in mouse prostate. We also found downregulation of testosterone induced antiapoptotic proteins, Bcl-2 and Survivin expression by [6]-gingerol in both LNCaP cells and in mouse ventral prostate. Thus, [6]-gingerol shows its protective effects in both in vivo and in vitro prostate cancer models by modulation of proteins involved in apoptosis pathway.

Cancer preventive properties of ginger: a brief review.

Ginger, the rhizome of Zingiber officinalis, one of the most widely used species of the ginger family, is a common condiment for various foods and beverages. Ginger has a long history of medicinal use dating back 2500 years. Ginger has been traditionally used from time immemorial for varied human ailments in different parts of the globe, to aid digestion and treat stomach upset, diarrhoea, and nausea. Some pungent constituents present in ginger and other zingiberaceous plants have potent antioxidant and anti-inflammatory activities, and some of them exhibit cancer preventive activity in experimental carcinogenesis. The anticancer properties of ginger are attributed to the presence of certain pungent vallinoids, viz. [6]-gingerol and [6]-paradol, as well as some other constituents like shogaols, zingerone etc. A number of mechanisms that may be involved in the chemopreventive effects of ginger and its components have been reported from the laboratory studies in a wide range of experimental models.