Ehrlich Ascites Tumor Cells Research Articles

Suppression of Ehrlich Ascites Tumor Cell Proliferation via G1 Arrest Induced by Dietary Nucleic Acid-Derived Nucleosides

Suppression of Ehrlich Ascites Tumor Cell Proliferation via G1 Arrest Induced by Dietary Nucleic Acid-Derived Nucleosides

Suppression of Ehrlich ascites tumor cell proliferation via G1 arrest induced by dietary nucleic acid-derived nucleosides.

The nucleic acids found in food play a crucial role in maintaining various bodily functions. This study investigated the potential anticancer effects of dietary nucleic acids, an area that is still not fully understood. By utilizing an in vivo mouse model and an in vitro cell model, we discovered an anti-proliferative impact of RNA in both systems. DNA exhibited anti-proliferative effects in the mouse model, while this phenomenon wasn't observed in the in vitro cell model using Ehrlich ascites tumor (EAT) cells. Conversely, DNA hydrolysate demonstrated distinct anti-proliferative effects in EAT cells, suggesting that nucleotides or nucleosides generated during nucleic acid digestion act as active constituents. Furthermore, we examined various nucleosides and two sodium-independent equilibrative nucleoside transporter inhibitors (ENTs), identifying guanosine and 2'-deoxyguanosine as pivotal in the anti-proliferative effect. We also found that the anti-proliferation activity with both nucleosides was suppressed by the treatment of dipyridamole, a non-selective inhibitor for ENT1 and ENT2, but not nitrobenzylthioinosine, a low inhibitor for ENT2. The uptake of these compounds into cells is likely facilitated by ENT2. These nucleotides impeded the progression of cancer cells from the G1 phase to the S phase in the cell cycle. Another significant finding is the increased expression of CCAAT/enhancer-binding protein (C/EBPβ) induced by guanosine and 2'-deoxyguanosine. Furthermore, immunostaining revealed that C/EBPβ diffuses into the nucleus, indicating its presence. This suggests that guanosine or 2-deoxyguanosine induces G1 arrest in cancer cells via the activation of C/EBPβ. Encouraged by these promising results, guanosine and 2'-deoxyguanosine show potential applications in cancer prevention.

Euphorbia grantii Oliv. standardized extract and its fraction ameliorate doxorubicin-induced cardiomyopathy in Ehrlich carcinoma bearing mice

Ethnopharmacological relevanceEuphorbia plants have long been used as traditional medicine in China, Europe, America, Turkey, India, Africa, Iran, and Pakistan because of its high medicinal value and health advantages especially as a remedy for several types of cancer. Aim of the studyDoxorubicin (DOX) is one of the most frequently prescribed drugs in cancer chemotherapy, with dose-limiting cardiotoxicity. The development of medicinal approaches to attenuate drug's toxicity represents an area of great concern in cancer research. Because research on this topic is still disputed and limited, we aim to investigate the potential of supplementation with Euphorbia grantii Oliv. on DOX-induced cardiomyopathy in Ehrlich carcinoma bearing mice. Materials and methodsThe high-performance thin layer chromatography (HPTLC) analysis of total methanolic extract (TE), and its bioactive dichloromethane fraction (DCMF) was applied for the determination of friedelin. Male BALB/c mice were used to keep the Ehrlich ascites tumor cells. The experiment was performed for a 2-weeks period. ResultsA good linearity relationship was found to be with correlation coefficient (r2) value of 0.9924 for the isolated friedelin. Limit of detection (LOD) and limit of quantitation (LOQ) was found to be 0.00179, and 0.000537 ng/band respectively for friedelin. The amount of friedelin in the TE and DCMF were determined by using calibration curve of standard as 106.32 ± 5.69 μg, and 159.2 ± 4.24 μg friedelin/mg extract, respectively. DOX-induced cardiomyopathy by decreasing the ejection fraction (EF) compared to the Ehrlich and negative control groups. It resulted in a decrease in the EF by 30 and 39% compared to the other groups. High and low doses of the TE and DCMF did not result in significantly different ejection fractions compared to the Ehrlich group. Co-administration of DCMF with DOX ameliorated the alteration in the serum CKMB and LDH levels. As revealed from histopathological study, DOX impairs viability of cardiac myocytes and DCMF could effectively and extensively counteract this action of DOX and potentially protect the heart from severe toxicity of DOX. ConclusionsFinally, our results indicated that Euphorbia grantii Oliv. would be the best option to reduce DOX adverse effects.

Fermented milk supplemented with water-soluble curcumin ameliorates survival rate, selected biochemical parameters and fecal microbiota of Ehrlich ascites carcinoma-bearing mice

This study assessed the impact of fermented cow and soy milk supplemented with curcumin on enhancement the health status of female Swiss mice under Ehrlich ascites carcinoma (EAC) condition. Both types of milk were fermented by Lactobacillus plantarum EMCC 1027. Ninety-five grams of basal diet mixed with five grams of either fermented cow or soy milk supplemented with curcumin. Induction of Ehrlich tumor-bearing mice synergized by intraperitoneal injection with 1 × 106 Ehrlich ascites tumor cells after one week of the adaptation period. Our results showed that levels of survival rate were increased to 117% in mice that were fed fermented cow and soy milk while supplementation of fermented soy milk with curcumin improved the survival rate to 150%. The concentration of glutathione and superoxide dismutase in Ehrlich tumor-bearing was increased after feeding with both types of fermented milk. Fermented soy milk supplemented with curcumin showed the highest reduction levels of plasma tumor necrosis factor (TNF)-α and interleukin-6. The relative gene expression TNF-α was also significantly (P < 0.05) down-regulated in mice that were fed fermented soy milk with curcumin. The viable count of lactobacilli and bifidobacteria in feces samples was increased when mice fed both types of fermented milk. Dietary feeding with fermented cow or soy milk supplemented with curcumin has an ameliorative impact on the survival rate, antioxidant capacity, inflammation, fecal microbiota in EAC mouse model. Further research is still needed to investigate the molecular mechanisms in this tumor.

The Role of Hyperthermia in Potentiation of Anti-Angiogenic Effect of Cisplatin and Resveratrol in Mice Bearing Solid Form of Ehrlich Ascites Tumour

The aim of this study was to investigate the therapeutic potential of resveratrol in combination with cisplatin on the inhibition of tumour angiogenesis, growth, and macrophage polarization in mice bearing the solid form of an Ehrlich ascites tumour (EAT) that were exposed to whole-body hyperthermia treatment. In addition, we investigated whether a multimodal approach with hyperthermia and resveratrol could abolish cisplatin resistance in tumour cells through the modulation of histone deacetylase (HDAC) activity and levels of heat shock proteins (HSP70/HSP90) and contribute to the direct toxicity of cisplatin on tumour cells. The tumour was induced by injecting 1 × 106 EAT cells subcutaneously (sc) into the thighs of Balb/c mice. The mice were treated with resveratrol per os for five consecutive days beginning on day 2 after tumour injection and/or by injecting cisplatin intraperitoneally (ip) at a dose of 2.5 mg/kg on days 10 and 12 and at a dose of 5 mg/kg on day 15. Immediately thereafter, the mice were exposed to systemic hyperthermia for 15 min at a temperature of 41 °C. The obtained results showed that the administration of resveratrol did not significantly contribute to the antitumour effect of cisplatin and hyperthermia, but it partially contributed to the immunomodulatory effect and to the reduction of cisplatin toxicity and to a slight increase in animal survival. This treatment schedule did not affect microvessel density, but it inhibited tumour growth and modulated macrophage polarization to the M1 phenotype. Furthermore, it abolished the resistance of tumour cells to cisplatin by modulating HDAC activity and the concentration of HSP70 and HSP90 chaperones, contributing to the increased lifespan of mice. However, the precise mechanism of the interaction between resveratrol, cisplatin, and hyperthermia needs to be investigated further.

Kaempferia galanga L. extract and its main component, ethyl p-methoxycinnamate, inhibit the proliferation of Ehrlich ascites tumor cells by suppressing TFAM expression

Kaempferia galanga L. shows anti-cancer effects; however, the underling mechanism remains unclear. In this study, we explored the underlying mechanism of the anti-cancer effects of Kaempferia galanga L. Kaempferia galanga L. rhizome extracts (KGEs) suppressed Ehrlich ascites tumor cell (EATC) proliferation by inhibiting S-phase progression. The main component of KGE is ethyl p-methoxycinnamate (EMC), which exhibits the same anti-proliferative effect as KGE. Furthermore, EMC induced the downregulation of cyclin D1 and upregulation of p21. EMC also decreased the expression of mitochondrial transcription factor A (TFAM) but did not significantly change mitochondrial DNA copy number and membrane potential. Phosphorylation at Ser62 of c-Myc, a transcription factor of TFAM, was decreased by EMC treatment, which might be due to the suppression of H-ras expression. These results indicate that EMC is the active compound responsible for the anti-cancer effect of KGE and suppresses EATC proliferation by regulating the protein expression of cyclin D1 and p21; TFAM may also regulate the expression of these genes. In addition, we investigated the anticancer effects of KGE and EMC in vivo using EATC bearing mice. The volume of ascites fluid was significantly increased by intraperitoneal administration of EATC. However, the increase in the volume of ascites fluid was suppressed by oral administration of EMC and KGE. This study provides novel insights into the association between the anti-cancer effects of natural compounds and TFAM, indicating that TFAM might be a potential therapeutic target.

Investigation of the effect of rhamnetin on mice injected with solid and ehrlich ascites tumor.

Rhamnetin is a flavonoid which contained in especially clove, such as apple, tea, and onion plant. Rhamnetin has been used in cancer research due to its antitumor and antioxidant properties. In this study, effects of rhamnetin administration at different doses on ascites and solid tumors were investigated in Balb/C mice bearing EAT model that originating from rat breast adenocarcinoma. Experimental procedure: Overall, 92 Balb-c mice were used in this study. EAT cells (1 × 106 cells) that harvested from stock animals were injected to all rats via intraperitoneal and subcutaneous route. Rhamnetin (100µg/kg-200µg/kg) were given intraperitoneally and subcutaneously during 10 and 15days to the animals bearing ascites tumor and solid tumor, respectively. Throughout experiments, weight changes were recorded in all groups. The maximum weight increase was observed in the control group among all groups (ascites and solid tumor groups). In the treatment groups, the least weight increase were determined in 200-µg/kg rhamnetin applied. The lowest increase in tumor volume was observed in the group that received 200-µg/kg rhamnetin (2.84) when compared to tumor control group (3.67). Result and conclusion: We determined that the number of live and dead cells in the treatment groups administered with the mean rhamnetin dose (2.5µg/ml) was found in the count made in the EAT cell line after the incubation periods. We observed that rhamnetin plays an important role against cancer formation. We have obtained important results in our study, but detailed studies on the relationship between rhamnetin and cancer are needed.

Investigating the anti-tumoral effect of yarrow (Achillea milllefolium) on the mice in which ehrlich solid tumor is created.

In this study, BALB/c mice with Ehrlich solid tumors were used to examine the effect of Achillea millefolium L. (AM) extract on the Ehrlich ascites tumor (EAT) model, which is one of the experimental cancer models. Also known as yarrow and plant, AM has antioxidant, anti-inflammatory, antibacterial and antitumor properties. In our study, 57 male BALB/c type mice, 8-10weeks old, weighing 25-30g, were used. Mice were divided into two groups. Ehrlich Solid Tumor group: Negative Control Group (ENC), Positive Control Group (EPC), and Treatment Group (TG) (TNCAM-200mg/kg, TPCAM-400mg/kg). EPC and TG were given to EAT cells. Each EAT contained 1 × 106 (will be 6 out of 10: so:000000) EAT cells, 0.1ml of phosphate-buffered saline (PBS) was administered subcutaneously (s.c.) to the nape of mice. Then It was awaited for solid tumor formation. AM extract was administered intraperitoneally (i.p.) to TG for 17days to mice. AM extract was found to have a curative effect on areas of inflammation, bleeding, and necrosis in treatment groups treated with AM extract alone. The treatment groups showed nearly normal histological results compared to the positive control group. According to the results, the TPCAM-400mg/kg group had a more significant histological impact than the TNCAM-200mg/kg group. In terms of tumor growth, tumor length, tumor volume, and tumor weight, AM extract did not show significant effects. However, in the light of histological findings, promising results of AM were observed in mice in which Ehrlich Solid Tumor was formed.

Evaluation of antitumoral effect of mistletoe fruit extract on Ehrlich ascites tumor cells with muse cell analyzer and argyrophilic nucleolar organizer region staining method

Abstract Introduction Mistletoe has been used alone or as a complementary therapy in the treatment of different diseases for years. In this study, the antitumoral effect of mistletoe fruit extract on Ehrlich ascites tumor (EAT) cells was evaluated. Materials and Methods EAT cells from preformed stock mice were transferred to culture dishes containing 5-fluorouracil (5-FU) and mistletoe extracts at different doses (100, 200, 400, and 800 μg/ml). These cells were incubated at 37 °C in an environment with 95% humidity and 5% CO2. At the end of the incubations, the apoptosis status of the cells, cell cycle, mitochondrial membrane potential, and proliferation status with the argyrophilic (Ag) nucleolar organizer region staining (NORs) method were evaluated. Results As a result, it was observed that the mistletoe fruit extract and 5-FU induce apoptosis of EAT cells. It was concluded that the 5-FU substance arrests the cell cycle at the G0/G1 stage, while the mistletoe arrests the cell cycle at the S and G2/M stages. The depolarization rate of the mistletoe treated cells was higher. As a result of the evaluation made with the AgNORs method, it was seen that mistletoe and 5-FU could be effective in reducing the proliferation of EAT cells. Conclusions It was seen that mistletoe fruit extract could be effective in stimulating the apoptosis and depolarization of cancer cells. The results of other studies in the literature and our study support each other. It was concluded that the mistletoe plant may be useful in cancer treatment.

Investigation of the protective and therapeutic effects of Lactobacillus casei and Saccharomyces cerevisiae in a breast cancer mouse model.

IntroductionThe development of novel strategies for cancer therapy is crucial to improve standard treatment protocols.AimThis study aimed to determine the protective and therapeutic effects of heat-killed preparations of Lactobacillus casei and Saccharomyces cerevisiae in a breast cancer mouse model.MethodsForty-two female BALB/c mice (7–8 weeks old) were divided into six groups (seven mice per group). Four groups were injected with 107 Ehrlich ascites tumor (EAT) cells suspended in phosphate-buffered saline (PBS) subcutaneously into the left side of the mammary fat pad. Tumor growth was monitored weekly until all animals developed a palpable tumor. The tumor-bearing mice in the experimental groups received heat-killed L. casei or S. cerevisiae three times per week for 35 days. The mice in the control group received PBS. The remaining two groups received heated L. casei or S. cerevisiae and then were injected with EAT cells. After 35 days, all mice were sacrificed to determine the immune response.ResultsAnimals that received heated S. cerevisiae exhibited the lowest rate of tumor growth compared with the other groups. TGF-β and IL-4 secretion was increased in all mice, whereas the secretion of INF-γ and IL-10 was decreased in breast tissues. Moreover, at the histopathological level, the volume of viable tumor in the control group was higher than in the treated groups.ConclusionSupplementary treatment with S. cerevisiae resulted in the best outcome in the breast cancer model compared with other treated and vaccinated groups.

Investigation of the effect of yarrow (Achillea millefolium) on Ehrlich ascites tumor

Abstract Introduction One of the most important health problems today is cancer. The aim of this study was to investigate the in vitro effect of yarrow (Y) with known anticarcinogenic effect on Ehrlich ascites tumor (EAT). Materials and Methods The above-ground part (300 g) of Y was macerated with water and extracted three times for 24 hours at 37°C in a shaking water bath. In the study, EAT cells were divided into control, DMSO group 5-FU, 50, 100, 200, 400 and 800 μg/ml YP groups. Results At the end of the hour, it was observed that total apoptosis increased significantly in Y groups (especially 50 μg/ml) compared to the control group (p&lt;0.05). It was observed that Y slowed the division of EAT cells (especially 800 μg/ml) by stopping the cell cycle at the G0/G1 stage. It was concluded that Y (especially at high doses) triggered apoptosis by significantly increasing the percentage of total depolarized cells (p&lt;0.001) in all three time periods. Conclusions The results obtained showed that Y extract may have an antitumoral effect on EAT cells. It is thought that this study will contribute to studies on cancer treatment.

Resveratrol and its nanocrystals: A promising approach for cancer therapy?

There has been a significant research interest in nanocrystals as a promising technology for improving the therapeutic efficacy of poorly water-soluble drugs, such as resveratrol. Little is known about the interaction of nanocrystals with biological tissue. The aim of this study was to investigate the potential use of resveratrol (RSV) and its nanocrystals (NANO-RSV) as antitumor agents in Ehrlich ascites tumour (EAT)-bearing mice and the interaction of nanocrystals with biological tissue through biochemical and histological changes of kidney, liver and EAT cells. After intraperitoneal injection of 2.5 × 106 cells into the abdominal cavity of mice, treatment of animals was started next day by injecting RSV or NANO-RSV at a dose of either 25 or 50 mg/kg every other day for 14 days. The results show that the administration of resveratrol and its nanocrystals lead to significant reductions in the proliferation of tumour cells in the abdominal cavity, and a reduction of the number of blood vessels in the peritoneum, with low systemic toxicity. In histopathological examinations, greater hepatocellular necrosis and apoptosis, hepatic fibrosis around the central vein and degeneration with minor fatty change were observed with RSV than with NANO-RSV. Inflammation with proximal tubular necrosis and renal glomerulus swelling were also observed, together with slight elevation of several biochemical parameters in both the RSV and NANO-RSV groups. In order to increase the beneficial effects and reduce risks associated with resveratrol nanocrystals, additional factors such as dose, genetic factors, health status, and the nature of the target cells should also be considered.

Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent

ObjectiveThe chemo-preventative and therapeutic properties of selenium nanoparticles (SeNPs) have been documented over recent decades and suggest the potential uses of SeNPs in medicine. Biogenic SeNPs have higher biocompatibility and stability than chemically synthesized nanoparticles, which enhances their medical applications, especially in the field of cancer therapy. This study evaluated the potential of green-synthetized SeNPs by using berberine (Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors (ESTs). MethodsSeNPs containing Ber (SeNPs-Ber) were synthesized using Ber and Na2SeO3 and characterized with Fourier transform infrared spectroscopy. Sixty male Swiss albino mice were then acclimatized for one week, injected with Ehrlich ascites tumor cells, and divided into four groups: EST, EST + cisplatin (5 mg/kg), EST + Ber (20 mg/kg), and EST + SeNPs-Ber (0.5 mg/kg). At the end of a 16-day observation period, 12 mice from each group were euthanized to analyze differences in the body weight, tumor size, gene expression, and oxidative stress markers in the four groups. Three mice from each group were kept alive to compare the survival rates. ResultsTreatment with SeNPs-Ber significantly improved the survival rate and decreased the body weight and tumor size, compared to the EST group. SeNPs-Ber reduced oxidative stress in tumor tissue, as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glutathione levels. Moreover, SeNPs-Ber activated an apoptotic cascade in the tumor cells by downregulating the B-cell lymphoma 2 (Bcl-2) expression rate and upregulating the Bcl-2-associated X protein and caspase-3 expression rates. SeNPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue, compared to the EST group. ConclusionOur study provides a new insight into the potential role of green-synthesized SeNPs by using Ber as a promising anticancer agent, these molecules could be used alone or as supplementary medication during chemotherapy.

Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release

BackgroundT cell-based immunotherapies using chimeric antigen receptors (CAR) or bispecific antibodies (BsAb) have produced impressive responses in hematological malignancies. However, major hurdles remained, including cytokine release syndrome, neurotoxicity, on-target off-tumor...

Immune stimulating and galectin-3 inhibitory effects of a hydrophilic polysaccharide nutraceutical from Tinospora cordifolia

Tinospora cordifolia is an important ayurvedic herb known for its immune stimulating effect. In this investigation, we describe the galectin-3 inhibitory and immune stimulating properties of a novel water-soluble nutraceutical made from Tinospora cordifolia stem. This proprietary extract (T2CA) had a total yield of 6% and contained 86.9% carbohydrates with a high proportion of patented (1,4)-α-D-glucan in it. The T2CA activated T-cytotoxic and NK cells significantly contributing to its immune stimulating effect. Moreover, T2CA induced the activation of functional NK cells in human lymphocyte cultures that in turn contributed to the death of K562 leukemic cells in a dose-dependent manner in co-culture experiments. T2CA inhibited the expression of phosphorylated galectin-3 expression in human glioblastoma cell line which in turn inhibits the activity of MMP2 and MMP9 proteins in zymography investigations and inhibits migration of cancer cells in in vitro scratch assay. Western blot hybridization studies showed that T2CA downregulates the expression of total gal 3 proteins and extended the survival of AKR/J mice injected with Ehrlich ascites tumor cells in the Kepler-Meier survival curve analysis. The inhibitory effect of T2CA on phopho-galectin-3 expression and the activation of T-cytotoxic and NK cells suggested its protective effects against pathogenic infections and human malignancies via its immune stimulating mechanisms.

Natural Phenolic Acid, Product of the Honey Bee, for the Control of Oxidative Stress, Peritoneal Angiogenesis, and Tumor Growth in Mice.

Tumor-associated macrophages (TAM) are key regulators of the link between inflammation and cancer, and the interplay between TAM and tumor cells represents a promising target of future therapeutic approaches. We investigated the effect of gallic acid (GA) and caffeic acid (CA) as strong antioxidant and anti-inflammatory agents on tumor growth, angiogenesis, macrophage polarization, and oxidative stress on the angiogenic model caused by the intraperitoneal (ip) inoculation of Ehrlich ascites tumor (EAT) cells (2.5 × 106) in Swiss albino mouse. Treatment with GA or CA at a dose of 40 mg/kg and 80 mg/kg ip was started in exponential tumor growth phase on days 5, 7, 9, and 11. On day 13, the ascites volume and the total number and differential count of the cells present in the peritoneal cavity, the functional activity of macrophages, and the antioxidant and anti-angiogenic parameters were determined. The results show that phenolic acids inhibit the processes of angiogenesis and tumor growth, leading to the increased survival of EAT-bearing mice, through the protection of the tumoricidal efficacy of M1 macrophages and inhibition of proangiogenic factors, particularly VEGF, metalloproteinases -2 and -9, and cyclooxygenase-2 activity.

Cornus Mas L improves Antioxidant Status in the Liver, Lung, Kidney, Testis and Brain of Ehrlich Ascites Tumor Bearing Mice.

Cornelian Cherry (Cornus Mas L) has widespread use due to its anti-inflammatory, anti-carcinogenic and anti-oxidant properties. In this study, the effects of Cornus Mas L (C. mas L) in different dosages on the biochemical values of mice organs were investigated in the Ehrlich Ascites tumor model, which originated from mice breast adenocarcinoma and developed in Balb/C mice. In our study, 32 Balb/C type male mice were used. Ehrlich Ascites Tumor (EAT) cells (1x106 EAT cell) from the stock animal were injected into all the mice in an intraperitoneal way. Experimental groups were given 100 and 200mg/kg C. mas L extract intraperitoneally for 9 days. The weights of the animals were recorded every day and were sacrificed on the 9th day. To estimate tumor proliferation of the lung, brain, kidney, liver, and testis, antioxidant parameters were recorded including, the reduced glutathione (GSH), lipid peroxidation, glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Treatments of different doses of C. mas L. meaningfully (p < 0.05) modulated the lung, brain, kidney, liver and testis tissues antioxidant parameters as compared to the control. Our study showed the anti-tumor effect of C. mas L. in assisted tumor development with EAT cells, conceivably moderated by the enhancement of oxidative stress due to numerous mechanisms.

A Comprehensive Review and Perspective on Anticancer Mechanisms of Withaferin A in Breast Cancer.

Withaferin A (hereafter abbreviated as WA) is a promising anticancer steroidal lactone abundant in a medicinal plant (Withania somnifera) native to Asia. The root/leaf extract of Withania somnifera, which belongs to the Solanaceae family, continues to be included in the Ayurvedic medicine formulations of alternative medicine practice. Numerous chemicals are detectable in the root/leaf extract of Withania somnifera [e.g., withanolides (WA, withanone, withanolide A, etc.), alkaloids, sitoindosides, etc.], but the anticancer effect of this medicinal plant is largely attributed to WA. Anticancer effect of WA was initially reported in the early 70s in the Ehrlich ascites tumor cell model in vitro Since then, numerous preclinical studies have been performed using cellular and animal models of different cancers including breast cancer to determine cancer therapeutic and chemopreventive effects of WA. Chemoprevention, a word first introduced by Dr. Michael B. Sporn, was intended to impede, arrest, or reverse carcinogenesis at its earliest stages with pharmacologic agents. This review succinctly summarizes the published findings on anticancer pharmacology of WA in breast cancer focusing on pharmacokinetic behavior, in vivo efficacy data in preclinical models in a therapeutic and chemoprevention settings, and its known effects on cancer-relevant cellular processes (e.g., growth arrest, apoptosis induction, autophagy, metabolic adaptation, immune function, etc.) and molecular targets (e.g., suppression of oncogenes such as estrogen receptor-α, STAT3, etc.). Potential gaps in knowledge as well as future research directions essential for clinical development of WA for chemoprevention and/or treatment of breast cancer are also discussed.

Natural bioactive 4-Hydroxyisophthalic acid (4-HIPA) exhibited antiproliferative potential by upregulating apoptotic markers in in vitro and in vivo cancer models.

There is tremendous scope for identifying novel anti-cancer molecules from the unexplored reserves of plant kingdom. The application of dietary supplementation or medicine derived from such sources is a promising approach towards treatment of cancer. In the present study we have evaluated the antiproliferative potential of 4-hydroxyisophthalic acid (4-HIPA), which is a novel antioxidant compound isolated from the roots of the aqueous extract of Decalepis hamiltonii. 4-HIPA was screened in vitro against human breast cancer cell lines MCF-7, MDA-MB-468 and normal human breast epithelial cell MCF-10, and demonstrated that human breast cancer cell lines, in contrast to MCF-10, are sensitive to 4-HIPA .4-HIPA showed marked reduction in cell viability and short-term proliferation assays in these cells. Results of the long-term colony formation and scratch assay further reaffirmed that 4-HIPA inhibited the growth and proliferation in breast cancer cells. We further conducted in vivo studies using murine Ehrlich Ascites Tumor (EAT) cell model. Our in vivo results established that treatment with 4-HIPA reduced the tumorigenesisby promoting apoptosis in EAT-bearing mice. The results of our molecular docking predictions further warranted our claim. This study is valuable as 4-HIPA exhibits antiproliferative potential that can be exploited in the development of anticancer drugs.

Effects of curcumin on lipid peroxidation and antioxidant enzymes in kidney, liver, brain and testis of mice bearing Ehrlich Solid Tumor

Introduction: Cancer is the second most common cause of death in the world. Several natural products have been studied for anticancer activity and for prevention or repair of oxidative injury. Curcumin is one of the natural products of high medicinal interest. This study was performed to investigate effects of curcumin on lipid peroxidation and antioxidant enzymes in tissues of mice bearing Ehrlich solid tumor. Materials and Methods: Forty mice were distributed to four groups as healthy control and treatments that received 1x106 Ehrlich ascites tumor (EAT) cells and EAT cells plus 25 mg/kg/day or 50 mg/kg/day curcumin with a single subcutaneous injection. The liver, kidney, brain and testis tissues were collected for the MDA, SOD and CAT analyses. Results: Tumor development increased MDA levels in liver (p=0.001), kidney (p&lt;0.001) and testis (p&lt;0.01) and curcumin reduced liver MDA. Liver and kidney SOD activities were increased by both levels of curcumin (p=0.001) but 50 mg/kg/day curcumin increased brain SOD activity (p&lt;0.001). The kidney CAT activity was increased by 50 mg/kg/day curcumin (p&lt;0.001). Discussion: This study showed that curcumin suppresses tumor progression, and alleviates the lipid peroxidation and improves antioxidant status in the tissues of solid tumor-bearing mice.