N-methyl-N-nitrosourea Research Articles

Antimetastatic effect of nanodiamond-conjugated quercetin against colon cancer: an in vivo study.

Quercetin (Q) is a compound that can inhibit the growth of cancer cells in the colon; however, to do so, a high dose is needed, requiring a drug delivery system to target cancer endothelial cells directly. This study investigates the potency of nanodiamond-conjugated quercetin (NDQ) as an anticancer drug against colon cancer in Rattus norvegicus induced by N-methyl N-Nitrosourea (MNU). This study is experimental-based and was designed using a six-group treatment method, namely normal control (KN: not treated by MNU, nanodiamond (ND), or Q); negative control (K-: treated by MNU); positive control (K+: treated by MNU and capecitabine); ND (treated by MNU and NDs); Q (treated by MNU and Q); and NDQ (treated by MNU and NDQ). To induce colon cancer in rats, MNU (10 mg/Kg BW) was administrated intrarectally three times per week for four weeks. The treatment of Q (40 mg/Kg BW) or NDQ (40 mg/Kg BW) was given intraperitoneally twice a week for 6 weeks. Cancer progression of all cohorts was evaluated by performing body and colon weight measurements, which involved the following: ELISA assay-specific to metastatic marker matrix metalloprotein-9 (MMP-9), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1 α (HIF1α), vascular endothelial growth factor, protein 53 (p53) and immunohistochemistry staining of Caspase-3 and Ki-67 proteins. Observation of cancer metastasis to the lung was also performed. NDQ significantly inhibited cancer aggressiveness by causing an increment in body weight gain and the growth rate-while reducing the colon weight compared to the K- group. Moreover, decreased levels of MMP-9, CEA, HIF-1α, and Ki67 and increased levels of p53 and Caspase-3 were more significant in the NDQ group than in the Q group. The lung tumor metastases in the NDQ group were fewer than in the K- group. NDQ increased Q's anticancer activity, suggesting that NDs have an effective drug delivery property.

Crocetin regulates cell cycle progression in N-nitroso-Nmethylurea(NMU)-induced breast cancer in rat: cyclin D1 suppression, p21Cip1 and p53 induction

Objectives: Crocetin, a saffron-derived carotenoid, inhibits tumor growth in some cancer types. However, its mechanism of action still needs to be clearly understood. Here, the Crocetin effect on the expression of some cell cycle regulators was investigated. Methods: The N-nitroso-N-methylurea (NMU)-induced rat mammary carcinomas were induced in a group of 35-day-old female Wistar Albino rats. Then, the expression of several cell cycle regulators was studied using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. After the tumor appearance, these rats were treated with Crocetin through weekly, intraperitoneal injections of 100 mg/kg body weight for four weeks. A control group has received the vehicle only. In the end, rats were sacrificed, and tumors were divided into two parts. A part was for pathologic investigation, and a part was retained at -70 °C to determine desired parameters. Results: Before Crocetin treatment, the tumor volumes were 13.27 ± 3.77 and 9.44 ± 4.39 cm3 , which was changed to 23.66 ± 8.82 and 4.71 ± 2.44 cm3 at the end of the experiment in the untreated and treated groups, respectively. The results showed that Crocetin markedly decreased the increased expression of cyclin D1 due to NMU administration. However, it further increased the expression of p53 and p21Cip1, with no significant effect on p27Kip1 expression. We previously showed Crocin-induced cell cycle arrest through a p53-dependent mechanism. Conclusion: Crocetin induced the cell cycle arrest in NMU-induced breast cancer in rats through a p53-independent mechanism. It is the second mechanism additional to apoptosis induction in cancer cells.

Integrin-Linked Kinase in the Development of Gastric Tumors Induced by Helicobacter pylori: Regulation and Prevention Potential.

Integrin-linked kinase (ILK) is crucial in solid tumors by regulating the Hippo-Yes-associated protein 1 (YAP) pathway. This study aimed to uncover how Helicobacter pylori influences ILK levels and its role in regulating YAP during H. pylori-induced gastric cancer. GES-1 cells with stable Ilk knockdown and overexpression and a mouse carcinogenesis model for H. pylori infection were constructed. And ILK, the phosphorylated mammalian STE20-like protein kinase 1 (MST1), large tumor suppressor 1 (LATS1; S909, T1079), and YAP (S109, S127) were detected in cells, and mice by western blotting, as well as fluorescence intensity of YAP were assayed by immunofluorescence. YAP downstream genes Igfbp4 and Ctgf, the pathological changes and tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), and nitric oxide (NO) levels in mice gastric tissues were detected by real-time PCR, H&E, and ELISA assays. In this study, stable Ilk knockdown cells exhibited significantly higher phosphorylated levels of MST1, LATS1, and YAP, as well as increased YAP in the nuclei of GES-1 cells. Conversely, cells with Ilk overexpression showed opposite results. H. pylori infection led to decreased ILK levels in gastric epithelial cells but increased ILK levels in gastric cancer cell lines (MGC803, SGC7901) and gastric cancer tissues in mice. Treatment with the ILK inhibitor OST-T315 elevated the phosphorylated MST, LATS1, and YAP levels, and inhibited the mRNA levels of Igfbp4 and Ctgf at 44, 48 week-aged mice. OST-T315 also reduced the release of TNF-α, IL-6, IL-1β, and NO, as well as the progression of gastric cancer caused by H. pylori and N-Nitroso-N-methylurea (NMU) treatment. Upon initiation of gastric tumorigenesis signals, H. pylori increases ILK levels and suppresses Hippo signaling, thereby promoting YAP activation and gastric cancer progression. ILK can serve as a potential prevention target to impede H. pylori-induced gastric cancer.

Chemopreventive effects of atractylenolide-III on mammary tumorigenesis via activation of the Nrf2/ARE pathway through autophagic degradation of Keap1

The incidence of breast cancer is increasing annually, making it a major health threat for women. Chemoprevention using natural, dietary, or synthetic products has emerged as a promising approach to address this growing burden. Atractylenolide-III (AT-III), a sesquiterpenoid present in various medicinal herbs, has demonstrated potential therapeutic effects against several diseases, including tumors, nonalcoholic fatty liver disease, and cerebral ischemic injury. However, its impact on breast cancer chemoprevention remains unexplored. In this study, we used an N-methyl-N-nitrosourea (NMU)-induced rat breast cancer model and 17β-estradiol (E2)-treated MCF-10A cells to evaluate the chemopreventive potential of AT-III on mammary tumorigenesis. AT-III inhibited mammary tumor progression, evidenced by reduced tumor volume and multiplicity, prolonged tumor latency, and the reversal of NMU-induced weight loss. Furthermore, AT-III suppressed NMU-induced inflammation and oxidative stress through the Nrf2/ARE pathway in breast cancer tissues. In vitro, AT-III effectively suppressed E2-induced anchorage-independent growth and cell migration in MCF-10A cells. Nrf2 knockdown attenuated the protective effects of AT-III, highlighting the pivotal role of Nrf2 in AT-III-mediated suppression of tumorigenesis. The mechanism involves the induction of Nrf2 expression by AT-III through the autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Overall, the results of this study indicate that AT-III is a promising candidate for breast cancer chemoprevention and provide valuable insights into its molecular interactions and signaling pathways.

Bloom syndrome DNA helicase mitigates mismatch repair-dependent apoptosis

Generation of O6-methylguanine (O6-meG) by DNA-alkylating agents such as N-methyl N-nitrosourea (MNU) activates the multiprotein mismatch repair (MMR) complex and the checkpoint response involving ATR/CHK1 and ATM/CHK2 kinases, which may in turn trigger cell cycle arrest and apoptosis. The Bloom syndrome DNA helicase BLM interacts with the MMR complex, suggesting functional relevance to repair and checkpoint responses. We observed a strong interaction of BLM with MMR proteins in HeLa cells upon treatment with MNU as evidenced by co-immunoprecipitation as well as colocalization in the nucleus as revealed by dual immunofluorescence staining. Knockout of BLM sensitized HeLa MR cells to MNU-induced cell cycle disruption and enhanced expression of the apoptosis markers cleaved caspase-9 and PARP1. MNU-treated BLM-deficient cells also exhibited a greater number of 53BP1 foci and greater phosphorylation levels of H2AX at S139 and RPA32 at S8, indicating the accumulation of DNA double-strand breaks. These findings suggest that BLM prevents double-strand DNA breaks during the MMR-dependent DNA damage response and mitigates O6-meG-induced apoptosis.

In-vivo anticancer activity of biosynthetic silver nanoparticles of Cassia marginata Roxb against NMU-Induced mammary carcinoma

The use of silver nanoparticles in the diagnosis and treatment of cancer is on the rise, and they are becoming more commonly recognized as effective therapeutic agents. Silver nanoparticles of Cassia marginata Roxb were prepared to investigate its anticancer potential in female Sprague-Dawley rats against N-nitroso N-methyl urea-induced mammary carcinoma. In this study, thirty animals were divided into five groups of six each: normal, disease control, Cassia marginata silver nanoparticles at 200 mg/kg, 400 mg/kg, and tamoxifen 10 mg/kg. N-nitroso N-methyl urea (50 mg/kg, i.p) was given twice at 52 days of age and four weeks after the prior treatment in 0.9 % NaCl. A total of two oral doses of Cassia marginata silver nanoparticles were administered, and the results were compared to the results of a single dose of tamoxifen (10 mg/kg, p.o). The tumor incidence rate, average tumor burden, and the total number of tumors were reduced in the treatment groups when compared with the disease control and the silver nanoparticles of Cassia marginata may prevent mammary carcinoma in Sprague-Dawley rats when exposed to N-nitroso N-methyl urea.

Histopathological Effect of Annona Muricata Fruit Extract on Methyl nitrosourea -Induced Mammary Gland Carcinoma in Female Albino Mice

The Annona muricata (Family-Annonaceae) fruit contain annonaceous acetogenins which have an effect on cancer cell as reported in many research studies. This study was aimed to evaluate the effect of methanolic fruit extract of Annona muricata (MFEAM) on breast cancer histology and invasive cell of MNU-induced breast cancer mice. Fifty female albino mice were divided into five groups (of ten each): control; MNU-induced breast cancer; MNU-induced breast cancer + (MFEAM) 200 mg/kg, MNU-induced breast cancer + (MFEAM) 300 mg/kg and MNU-induced breast cancer + (MFEAM) 500 mg/kg. The research indicates that breast cancer invasive ductal carcnoma (IDC) developed in the MNU-induced breast cancer group. The control group showed normal duct structure. The (MFEAM) -treated group showed lower invasive (DCIS) compared with the untreated cancer group. We concluded that (MFEAM), that improved the histological changes of breast cancer-induced MNU. Also (MFEAM) reduced proliferative epitheal cell of breast cancer-induced MNU and the most effective dose was 300 mg/kg. The present study concluded that the methanol extracts derived from Annona muricata fruit potentially exhibit antitumor activity. The control group showed normal duct structure. The (MFEAM) -treated group showed lower invasive (DCIS) compared with the untreated cancer group, We concluded (MFEAM) that improved the histological changes of breast cancer-induced MNU. Also (MFEAM) reduced proliferative epitheal cell of breast cancer-induced MNU and the most effective dose in 300 mg/kg.

Mutation types and frequency in Nigella damascena L. in the М2 and M3 generation, using ethyl methanesulfonate, nitrosomethylurea and a new derivative of dimethylsulfate, DG-2

Aim. To identify mutations and evaluate the mutation frequency in Nigella damascena L. cultivars (cvs) Bereginya and Charivnytsya (M2 and M3 generation), following treatment of their seeds with ethyl methanesulfonate (EMS), nitrosomethylurea (NMU) and a new derivative of dimethyl sulfate, DG-2. Methods. Treated Nigella seeds of two cvs with the mutagens for 6 and 16 h and in concentrations of 0.01 and 0.5 % for EMS and NMU and 0.05 and 0.5 % for DG-2. Results. A wide range of mutations (59 types) was obtained, that was divided into six groups: five groups with changes in the morphological type and one group with changes in the physiological type. Among the detected mutations, there were both previously known mutations and those obtained in this culture for the first time. The high- est mutation frequency (30 %) affecting synthesis of chlorophyll and structure of stem, shoots and leaves and 20 % for physiological features, was registered for NMU at 16 h and 0.05 % in cv. Bereginya. However, this NMU concentra- tion appeared to be lethal for cv. Charivnytsya. Conclusions. The new mutagen DG-2 proved to be most effective for inducing mutations in the corolla petal color of nigella, namely 4.0 at a 0.5 % concentration of the mutagen and 16h exposure for cv. Bereginya and 4.0 % at the same concentration and exposure for cv. Charivnytsya. DG-2 caused a substantial number of mutations in all six mutation groups affecting morphological and physiological traits. The clas- sic mutagen EMS was also effective across the spectrum of mutation groups in our study; however, it caused mutations at a lower frequency. The maximum mutation frequency under influence of EMC at a concentration of 0.05 % and an exposure of 16 h in cv. Bereginya was 11.0 %, and in cv. Charivnytsya 8.0 %. For all three mutagens used, an increase in the concentration of the active substance and of exposure time led to an increase in the mutation frequency in N. damascena plants. We will select mutants with economically valuable traits, such as tall, lodging-resistant plants and early maturing ones, for further work on the development of new cultivars of N. damascena for industrial cultivation.

The regeneration-responsive element careg monitors activation of Müller glia after MNU-induced damage of photoreceptors in the zebrafish retina.

In contrast to mammals, zebrafish can regenerate their damaged photoreceptors. This capacity depends on the intrinsic plasticity of Müller glia (MG). Here, we identified that the transgenic reporter careg, a marker of regenerating fin and heart, also participates in retina restoration in zebrafish. After methylnitrosourea (MNU) treatment, the retina became deteriorated and contained damaged cell types including rods, UV-sensitive cones and the outer plexiform layer. This phenotype was associated with the induction of careg expression in a subset of MG until the reconstruction of the photoreceptor synaptic layer. Single-cell RNA sequencing (scRNAseq) analysis of regenerating retinas revealed a population of immature rods, defined by high expression of rhodopsin and the ciliogenesis gene meig1, but low expression of phototransduction genes. Furthermore, cones displayed deregulation of metabolic and visual perception genes in response to retina injury. Comparison between careg:EGFP expressing and non-expressing MG demonstrated that these two subpopulations are characterized by distinct molecular signatures, suggesting their heterogenous responsiveness to the regenerative program. Dynamics of ribosomal protein S6 phosphorylation showed that TOR signaling became progressively switched from MG to progenitors. Inhibition of TOR with rapamycin reduced the cell cycle activity, but neither affected careg:EGFP expression in MG, nor prevented restoration of the retina structure. This indicates that MG reprogramming, and progenitor cell proliferation might be regulated by distinct mechanisms. In conclusion, the careg reporter detects activated MG, and provides a common marker of regeneration-competent cells in diverse zebrafish organs, including the retina.

Chemo-preventive Activity of Ethanolic Extracts of Newbouldia laevis and Olax subscorpioidea Leaves on Methylnitrosourea–induced Stroma Fibrosis in Breast Tissues of Female Albino Rats

Breast cancer represents the most common neoplastic disease in females, accounting for up to one third of new diagnoses of women’s cancer in certain regions of the world. The chemo-preventive activity of ethanolic extracts of Newbouldia laevis and Olax subscorpioidea leaves on methylnitrosourea (MNU)–induced stroma fibrosis in female albino rats was evaluated. Quantitative and qualitative phytochemical screening was carried out to identify and determine the quantity of bioactive compounds. Haematoxylin and Eosin staining procedure was used to assess breast tissues of experimental animals. Cancer antigen (CA) markers 15-3, 27-29 and carcinoembryonic antigen (CEA) in the blood of experimental animals were evaluated using an automated procedure. Quantitative phytochemical screening showed that Olax subscorpioidea and Newbouldia laevis contained alkaloid in the highest amount. Histopathological assay revealed the presence of stromal fibrosis in the breast tissues of 8 out of 10 rats administered with NMU. Levels of CA 15-3, CA 27-29, CEA were significantly (p < 0.05) elevated in MNU administered group in comparison to the negative control. Treatment with Olax subscorpioidea leave extract significantly (p < 0.05) ameliorated CA 15-3, CA 27-29 and CEA levels. However, treatment with Newbouldia laevis leave extract significantly (p < 0.05) ameliorated CA 15-3 and CEA levels only. Findings from this study showed that ethanolic extracts of Olax subscorpioidea and Newbouldia laevis leaves have chemo-preventive activity in NMU-induced stroma fibrosis in the breast tissue of female albino rats. However more studies on the discovery and validation of bioactive components of the plants are needed.

Effect of Curcuma longa on T lymphocytes in rats induced to prostate cancer

Worldwide, prostate cancer is the second most diagnosed type of cancer in the male population, as well as the fifth leading cause of death. Therefore, it is necessary to look for alternatives for its prevention and treatment. Objective: to determine the effect of the pulverized rhizome of Curcuma longa on T lymphocytes in an animal model of prostate cancer. Methodology: It is an experimental study, 30 male rats Holtzman from 10 to 12 weeks of age were used, with an average weight of 200 to 250 g. Prostate cancer induction was performed by administration of testosterone, progesterone, and N-nitroso-N-methylurea (NMU) at doses of 100 mg/kg, 50 mg/kg, and 50 mg/kg, respectively. The pulverized rhizome of Curcuma longa was administered in aqueous solution at doses of 200, 400 and 600 mg/kg. Determination of CD4+ and CD8+ T cells was analyzed by BD FACSCalibur flow cytometry using FlowJo software. Results: Curcuma longa at different doses significantly improved the percentage of CD4+ and CD8+ T lymphocytes in the animals that received the treatments, increasing the population subgroups by 50 to 100%. Likewise, a better effect on the inhibition of tumor growth was presented at the dose of 600 mg/kg. Conclusion: an increase in T lymphocytes by Curcuma longa was evidenced at all the doses tested, presenting better results at the dose of 600 mg/kg.

Asymmetric Dimethylarginine in an NMU-induced Rat Mammary Tumor Model.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) production and a newly discovered risk factor involved in endothelial dysfunction and adverse cardiovascular events. Recently, both NO and ADMA have also emerged as molecules of interest in carcinogenesis and tumor growth progression. Our earlier studies have confirmed elevated plasma ADMA levels in patients with hematological malignancies. However, the cause of elevated ADMA was unclear. The aim of this study was to assess the concentrations of ADMA, symmetric dimethylarginine (SDMA) and L-arginine in rats exposed to N-nitroso-N-methylurea (NMU) for the induction of mammary tumors. A total of 95 female rats of the Sprague-Dawley strain were used in the study. Plasma concentrations of ADMA, SDMA and L-arginine were quantified and statistically analyzed. Mean ADMA levels were higher in the tumor-bearing group compared to the control group. Mean plasma levels of SDMA and L-Arginine were not significantly different between the groups. The L-ARG/ADMA ratio was lower in rats with tumors compared to controls. Histological assessment confirmed expression of ADMA within the tumor cells, which strongly suggests that these tumor cells were the source of ADMA. Other studies are warranted to further explain the role of ADMA in neoplastic diseases.

Increasing the effect of annonacin using nanodiamonds to inhibit breast cancer cells growth in rats (Rattus norvegicus)-Induced breast cancer

BackgroundAnnonaceous acetogenins have been reported to have anti-cancer properties but low viability. In this study, we aimed to investigate the potency of nanodiamonds to be employed as a carrier of annonacin to help increase its viability and inhibit the growth of breast cancer cells. MethodsThe annonacin was coupled with nanodiamond and characterized using UV-Vis spectrophotometer, FTIR, SEM, and PSA, and determined their stability and drug release. A cell growth inhibition assay and cell migration assay was performed using the breast cancer MCF7 and T747D cell lines, and in vivo analysis was performed in rats (Rattus norvegicus). MCF7 and T747D cells were treated with 12.5 μg/mL annonacin coupled with nanodiamonds for 24 and 48 h and further analyzed by MTT, cell migration, and reactive oxygen species (ROS) assays. Twenty-five female rats were divided into five groups. Breast cancer was induced using two intraperitoneal doses of N-nitroso-N-methylurea (NMU) (50 and 30 mg/kg body weight). Annonacin coupled with nanodiamonds was administered by intraperitoneal injection (17.5 mg/kg body weight) for 5 weeks, one injection per 3 days. ResultsAdministration of annonacin coupled with nanodiamonds significantly reduced MCF7 cell growth and reactive oxygen species (ROS) levels. The in vivo study showed that administration of annonacin coupled with nanodiamonds significantly reduced PI3KCA levels and increased p53 expression, reduced cancer antigen-15-3 (CA-15-3) levels in serum, increased caspase-3 expression, reduced Ki-67 levels, and reduced the thickness of the mammary ductal epithelium. ConclusionsCollectively, this study demonstrated the effectiveness of nanodiamonds as a carrier of annonacin to inhibit breast cancer cell growth through inhibition of the PI3K/Akt signaling pathway.

Enhancing the Anticancer Activity of Squamocin for Breast Cancer Treatment Using Nanodiamond Nanoparticles: An In Vivo Study

Squamocin is one of the annonaceous acetogenins produced by the Annonaceae family and displays potent anti-cancer activity against cancer cell lines. This study aimed to investigate the growth inhibition activity of squamocin coupled with nanodiamond on rats (Rattus norvegicus)-induced breast cancer. Twenty-five female R. norvegicus were divided into five groups (n = 5), including normal control (without any treatment), negative control, group treated with nanodiamond only (ND), group treated with squamocin only (SQ), and the group treated with squamocin coupled with nanodiamond (NDSQ). All of the animal models were induced for breast cancer, except for the normal control group. Breast cancer induction was performed using two doses of N-nitroso-N-methylurea (NMU) injection (50 and 30 mg/kg body weight) intraperitoneally and waited for 22 weeks until the tumor was detected to formed. Nanodiamond coupled with squamocin were administered by intraperitoneal injection (1.5 mg/kg body weight) for 5 weeks, one injection per 3 days. This study showed that the treatment with squamocin coupled with nanodiamond (NDSQ) significantly reduced the proliferation (Ki-67) and induced apoptosis (Caspase-3) of breast cancer cells, corresponding to the reduction of the thickness of the mammary ductal epithelium (p<0.001) and the lower level of CA-153 in serum. In addition, the treatment significantly reduced the malondioldehyde (MDA) and PI3KCA and increased the p53 level significantly. Altogether, in this study, we are the first to report the anti-cancer activity of squamocin in rat-induced breast cancer and the potency of nanodiamond as a carrier of squamocin to increase its anti-cancer activity.

Anticancer activity of Alpinia purpurata (Vieill) K. Schum. against MNU and testosterone induced prostate cancer in male Wistar albino rats

BackgroundNumerous Chinese herbal extracts have been proved to inhibit the development of prostate cancer. Zingiberaceae family is one type of plant used as an ingredient in traditional Chinese medicine (TCM). The genus Alpinia species of the Zingiberaceae family are well-known traditional herbal medicine for anti-inflammatory, antioxidant, antimicrobial, anti-dermatophytic, anti-nociceptive, hepatoprotective, immune stimulatory and anticancer activities. In vivo anticancer activity of Alpinia purpurata were studied in MNU and testosterone induced prostate cancer rats. MethodsThe induction of prostate cancer by using Wistar strain rats. The animals were divided into five groups. Group 1- Control, normal healthy rats Group 2- Rats were induced prostate cancer by daily intraperitoneal injection of testosterone (T) (100 mg/kg bw) in 0.3 ml propylene glycol for 3 days. One day after the testosterone injection, all the rats received intravenous injection of N-methyl N-nitrosourea (MNU) (50 mg/kg bw) (dissolved in saline at 10 mg/ml), through the tail vein for a period of one week. One week after MNU administration, rats received daily intraperitoneal injection of 2 mg/kg bw testosterone for 60 days. Group 3 - Rats were treated as group 2 along with Finasteride (25 mg/kg bw) supplemented throughout the entire experimental period of 2 months. Group 4 - Rats were treated as group 2 and simultaneously treated with daily dose of 200 mg/kg bw of the crude leaf ethyl acetate extract of Alpinia purpurata through oral gavage for 2 months. Group 5 - Rats were received daily dose of 200 mg/kg bw of crude, leaf ethyl acetate extract of Alpinia purpurata through oral gavage for 2 months. After the experimental period of 4 months, the animals were sacrificed by cervical dislocation under mild chloroform anesthesia. All biochemical parameters and histopathological studies were carried out. ResultsThe biochemical parameters such as total protein, enzymatic and non-enzymatic antioxidants and membrane bound enzymes were decreased whereas LPO, tumor markers, nucleic acid constituents were increased in prostate and seminal vesicle tissues of cancer induced group. The hematological, lipid parameters were altered and prostate markers, renal markers and liver markers were increased in serum. Those levels were brought back to near normal upon treatment with ethyl acetate leaf extract of Alpinia purpurata and standard drug finasteride. No significant changes were observed on treatment with plant extract alone group which indicated that there is no toxic substance present in Alpinia purpurata which was confirmed by the histopathological analysis of organs liver, kidney, prostate gland and seminal vesicle. ConclusionOn the basis of our findings, it is concluded that Alpinia purpurata might be used as an anticancer agent for the management of carcinoma in future.

Chemo-Protective Effects of Dl-Limonene Unaided and in-Blend with 6-Methyleneandrosta-1, 4-Diene-3, 17-Dione on N-Nitroso-N-Methylurea and Estrogen Sulfotransferase Breast Cancer-Induced Albino Female Rat

Breast cancer is a serious prime hassle commonly diagnosed in women worldwide and it is currently the leading cause of cancer-related mortality. In N-nitroso-N-methylurea (NMU) and estrogen sulfotransferase (EST) breast cancer-induced female rat, the study evaluates the chemo-protective possibilities of DL-limonene (1:1) and its combination with 6-Methyleneandrosta-1, 4, Diene- 3, 17-Dione using standard techniques. Amongst others, data obtained reveals mild areas of clogged blood vessels and pulmonary inflammation revealed in the histopathology section. Interestingly, it's possible that DL-limonene alone at a concentration of 10% could be an effective breast cancer treatment. The findings also revealed that combining DL-limonene with 6-ADD at 5% and 12.5mg/kg could reduce the risk of toxicity associated with higher chemotherapeutic dosages in long-term treatment. Furthermore, at a modest dose, this combination may increase the use of aromatase inhibitors in premenopausal women. Despite the medicinal and therapeutic benefits of DL-limonene, it is best to take it in moderation due to its possible harmful effects on the blood vessels.

Wedelolactone Attenuates N-methyl-N-nitrosourea-Induced Retinal Neurodegeneration through Suppression of the AIM2/CASP11 Pathway.

N-methyl-N-nitrosourea (NMU) is widely used to model oxidative stress and inflammation mediated retinal neurodegeneration. Wedelolactone (WD) is known to have antioxidant, anti-inflammatory, and neuroprotective roles. This study tested the therapeutic potential of WD in NMU-induced retinal neurodegeneration and investigated the underlying mechanisms in mice. NMU (40 mg/kg) was injected intraperitoneally into C57BL/6J mice with/without an intravitreal injection of WD (1 μL/eye, 200 μM). Seven days later, retinal function and structure were evaluated by electroretinography (ERG) and Spectral Domain Optical Coherence Tomography (SD-OCT). The expression of inflammasome components (Aim2, Caspase 1/11, and Il1b/Il18) in the total retina lysate was evaluated by RT-qPCR. In vitro, 661W photoreceptor cells were transfected with synthetic double-strand DNA (Poly(dA:dT)) with/without WD pre-incubation. The aim2-related inflammasome expression was evaluated by RT-qPCR and immunocytochemistry. The production of IL18 was measured by ELISA. NMU treatment significantly impaired A- and B-wave response (ERG) and reduced neuroretina thickness (OCT). This was significantly attenuated upon intravitreal injection of WD. The expression of Aim2, ACasp1, and Casp11 was increased in the retina from NMU-treated mice, and this was prevented by WD treatment. Transfection of Poly(dA:dT) upregulated Aim2, Casp11, and Il18 expression in 661W cells. WD prevented their upregulation and reduced IL18 production. Aim2 inflammasome activation is critically involved in NMU-induced retinal neurodegeneration and WD can protect the retina particularly through the suppression of this inflammasome-linked pathway.

Probing Transferrin Receptor Overexpression in Gastric Cancer Mice Models.

Exposure to carcinogenic chemicals, Helicobacter pylori infection, and high dietary salt are the risk factors associated with gastric cancer. Mice models of gastric cancer are key to understanding the cancer mechanism, to discerning the role played by different factors, and to determining therapeutic effects of different treatments. The goal has been to find targets which are only expressed with cancer so that they can be targeted specifically without harming normal cells. One such target could be the transferrin receptor, a glycoprotein receptor that is expressed many-folds on rapidly growing cells due to the greater demand of iron. In this study, gastric cancer was developed in mice (BALB/c) with human cancer-associated risk factors by feeding them with tumor-inducing concentration of methyl nitrosourea, dietary salt, and H. pylori along with normal feed and water. Three strategies were adopted to induce gastric cancer; (1) use of N-methyl-N-nitrosourea (MNU) with high dietary salt (NaCl), (2) infection with H. pylori (isolated from human gastric tissue), and (3) use of MNU along with high concentration of NaCl after H. pylori infection. Mice were dissected after induction, and histological study of gastric tissue was done with Hematoxylin and Eosin staining. A diagnostic probe comprising transferrin conjugated with cadmium sulfide quantum dots was prepared and characterized. It was used to study the transferrin receptor overexpression in gastric tissue of cancer-induced mice relative to the normal mice. Mice of group 3 showed the highest rate of the cancer incidence ratio (96%) along with a high expression of transferrin receptors among the three groups. Histochemical studies showed that different types of gastric cancer depend upon the cancer-induction conditions. The mouse model of group 3 has the potential to be used in the future to study the therapeutic effects of cancer medicines, and overexpression of transferrin receptors could be identified through the designed probe to be used as diagnostics.

Spontaneous macromutants "soft wheat" or a complete homolog of Tritcum kiharae Dorof. et Migusch

For the successful development of breeding, a genetically diverse source material is necessary. The decline in genetic diversity is a global problem affecting most cultivated crops, including wheat. In this regard, the creation of a homologous soft wheat form for the second phylogenetic branch is very attractive, since it will be a valuable source material for the selection improvement of Triticum aestivum L.. AuBD. Previously derived from T. kiharae Dorof. et Migusch., AbGD under the influence of N-HMM (nitrosomethyl urea), the complete homologue showed phenomenal both phenotypic and certain genotypic similarity to soft wheat and easily crosses with the varieties of the latter. Later, the homologous form of soft wheat obtained from it under the influence of colchicine, despite its phenotypic proximity to the latter, looked like an intermediate form. Spontaneous macromutants "soft wheat" are shown, isolated, in the first case, from T. kiharae plants that have previously changed color, and, in the second, from the so-called intermediate form. The identified soft wheat macromutants were significantly superior in their production characteristics to the original T. kiharae and can also be used as a starting material to improve the characteristics of T. aestivum.

Chloroform extract of Calliandra portoricensis inhibits tumourigenic effect of N-methyl-N-nitrosourea and benzo(a)pyrene in breast experimental cancer

Calliandra portoricensis (C. portoricensis) is used in herbal homes in Nigeria to manage breast diseases. We investigated the anti-tumourigenic effects of chloroform extract of C. portoricensis (CP) in breast experimental cancer induced by N-methyl-N-nitrosourea (NMU) and benzo-(a)-pyrene (BaP). Fifty-six female rats were assigned into seven equal groups: Group 1 served as control, group 2 received NMU and BaP (50 mg/kg, each), groups 3 and 4 received [NMU + BaP] and treated with CP at 50 and 100 mg/kg, respectively. Group 5 received CP (100 mg/kg), group 6 received [NMU + BaP] and vincristine (0.5 mg/kg), while group 7 received vincristine (0.5 mg/kg). The NMU and BaP (i.p) were dissolved in normal saline and corn oil, respectively. The CP (oral) and vincristine (i.p) were given thrice and twice per week, respectively for 10 weeks. The [NMU + BaP] intoxication significantly decreased body weight gain by 32% while organo-somatic weight of mammary gland increased by 37%. Also, [NMU + BaP] decreased the activities of mammary catalase, glutathione-s-transferase, glutathione peroxidase, superoxide dismutase and total sulphurhydryl by 34%, 31%, 35%, 35% and 33%, respectively. The [NMU + BaP] increased inflammatory and oxidative stress markers; nitrite, lipid peroxidation and myeloperoxidase by 62%, 57% and 361%, respectively. Strong expression of BCL-2, IL-6, COX 2, β-catenin and iNOS in [NMU + BaP]-administered rats were observed. Histology revealed glands with malignant epithelial cells and high nucleocytoplasm in [NMU + BaP] rats. Treatment with CP attenuated inflammation, apoptosis and restored cyto-architecture of mammary gland. Overall, CP abates mammary tumourigenesis by targeting cellular pathways of inflammation and apoptosis.