Preventive Effect of Combined Zingiber officinale and Terminalia chebula against DMBA-Induced Breast Cancer Rats via mTOR Inhibition.
TL;DR: In this paper, the preventive effect of Zingiber officinale-Terminalia chebula extract (ZOTC) against DMBA-induced breast cancer in a rat model was investigated.
Abstract: Zingiber officinale (ZO) and Terminalia chebula (TC) are plants used for the treatment of diverse illnesses in traditional medicine. The present study investigates the preventive effect of Zingiber officinale-Terminalia chebula extract (ZOTC) against DMBA-induced breast cancer in a rat model. Bioactive compounds from ZO (6-gingerol, 6-shogaol) and TC (gallic acid, ellagic acid, corilagin, chebulinic acid, and chebulagic acid) were detected using high-performance liquid chromatography. Mammary carcinogenesis was induced in rats with a single subcutaneous injection of 7,12-Dimethylbenz[a]anthracene (DMBA). Oral administration of ZOTC ameliorated the antioxidant status in mammary tissues, serum lipid levels, and serum cytokines. Histological analysis of the mammary tissue (normal and tumor) was carried out to obtain pathological alterations due to ZOTC treatment. The effect of ZOTC on the mechanistic target of rapamycin (mTOR) gene and accumulation of corresponding gene product was also investigated. mTOR plays a central role in cell metabolism and proliferation in normal and cancer cells. Transcriptional and immunohistochemical analysis showed the downregulation of mTOR expression in the mammary tissues of ZOTC-treated rats. In conclusion, the results obtained suggest that ZOTC can suppress tumor progression in DMBA-induced breast cancer rats via inhibition of the mTOR pathway.
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TL;DR: The NCHDH and NTHDH significantly improved the DMBA‐induced breast cancer via attenuating oxidative stress and inflammatory cytokines and enhanced the antioxidants signaling proteins such as nuclear factor erythroid 2–related factor 2 (Nrf2) and Heme oxygenase 1 (HO‐1).
Abstract: The present study investigated the effect of the N‐(benzylidene)‐2‐((2‐hydroxynaphthalen‐1‐yl)diazenyl)benzohydrazides (1‐2) (NCHDH and NTHDH) against breast cancer using in vitro and in vivo approaches. The NCHDH and NTHDH significantly inhibited the growth of the MCF‐7 cells using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. The NCHDH and NTHDH treatment significantly inhibited the tumor size, tumor weight, and tumor volume, while it enhanced the survival and tumor free survival rate following 7,12‐Dimethylbenz[a]anthracene (DMBA)‐induced breast cancer. The NCHDH and NTHDH markedly attenuated the oxidative stress markers and induced the antioxidant level. The enzyme‐linked immunosorbent assay (ELISA) showed significant reduction in the inflammatory cytokines production compared with the DMBA control. The NCHDH and NTHDH treatment significantly improved the histological features using hematoxylin and eosin (H and E) staining, Masson's trichrome, PAS (periodic acid Schiff), and Toluidine blue staining compared with the DMBA‐induced group. The NCHDH and NTHDH treatment improved the hematological and serological parameters following DMBA‐induced breast tumor compared with DMBA‐induced group. Furthermore, the NCHDH and NTHDH treatment significantly enhanced the antioxidants signaling proteins such as nuclear factor erythroid 2–related factor 2 (Nrf2) and Heme oxygenase 1 (HO‐1). The NCHDH and NTHDH enhanced the inhibitor of NF‐κB (IκB) level, while it attenuated the NF‐κB level. Similarly, the NCHDH and NTHDH showed marked increase in the apoptosis proteins such as Caspase‐3, Caspase‐9, and Bcl‐2 Associated X‐protein (Bax), while it inhibited the B‐cell lymphoma 2 (Bcl‐2) expression. In conclusion, the NCHDH and NTHDH significantly improved the DMBA‐induced breast cancer via attenuating oxidative stress and inflammatory cytokines.
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TL;DR: In this paper , the potential therapeutic and chemosensitizing effects of geraniol on breast carcinoma induced in mice through examination of tumour biomarkers and histopathology profile were investigated.
Abstract: OBJECTIVES
Breast cancer is the most diagnosed cancer in females worldwide. Phytochemicals are among the recent compelling approaches showing anticancer activity. Geraniol is a monoterpenoid showing anti-tumoral potential in cell lines. However, its exact mechanism in breast cancer has not been elucidated. In addition, the possible chemosenstizing effect of geraniol when combined with chemotherapeutic drugs in breast carcinoma has not been previously addressed.
METHODS
Therefore, the aim of the current work is to investigate the potential therapeutic as well as chemosensitizing effects of geraniol on breast carcinoma induced in mice through examination of tumour biomarkers and histopathology profile.
KEY FINDINGS
Results showed a prominent suppression of tumour growth following geraniol treatment. This was accompanied with miR-21 downregulation that subsequently upregulated PTEN and suppressed mTOR levels. Geraniol was also able to activate apoptosis and inhibit autophagy. Histopathological examination revealed high necrosis areas separating malignant cells in the geraniol-treated group. Combined geraniol and 5-fluorouracil treatment induced more than 82% inhibition of tumour rate, surpassing the effect of each drug alone.
CONCLUSIONS
It can be concluded that geraniol could represent a promising avenue for breast cancer treatment as well as a potential sensitizing agent when combined with chemotherapeutic drugs.
TL;DR: Amaç et al. as discussed by the authors presented a study on the ekspresyonning of mRNA in klinik and found that it is an important research topic in the field of cancer research.
Abstract: Amaç: Bu çalışma, meme kanserinde insan telomeraz ters transkriptaz (hTERT) genin mRNA ekspresyonunun klinik önemini incelemeyi ve klinikopatolojik rolünü araştırmayı amaçlamıştır. hTERT geni hücre proliferasyonu, apoptoz ve hücre invazyonu gibi olaylarda rol almaktadır. Yüksek hTERT mRNA ekspresyonunun meme kanseri, mide, akciğer, glioblastoma, baş ve boyun gibi solid tümörlerde kötü prognoz ile ilişkili olduğu bildirilmektedir.
Gereç ve Yöntemler: 59 meme kanser ve sağlıklı kan örneklerinin RNA izolasyonları gerçekleştirildi. hTERT geni mRNA ekspresyonu Gerçek Zamanlı Polimeraz Zincir Reaksiyonu (RT-PZR) yöntemi ile analiz edildi. mRNA ekspresyon sonuçları 2-∆∆ct metoduyla kanserli ve sağlıklı örneklerde değerlendirildi. Klinik veriler toplandı ve bu verilerin hTERT gen ekspresyonu ile ilişkisi istatiksel olarak değerlendirildi.
Bulgular: Meme kanser hastalarında hTERT geni mRNA ekspresyonu sağlıklı örneklere kıyasla anlamlı derecede yüksekti (p=0,0211). Düşük hTERT geni ekspresyonu östrojen reseptör (ÖR) (+) ve insan epidermal büyüme faktör reseptörü 2 (HER 2) (+) olan hastalarda anlamlı derecede ilişkiliydi (sırasıyla p=0,0464; p=0,0080). hTERT geni ekspresyonu histolojik derece (grade) 3 hastalarda derece 2’ye kıyasla yüksek anlamlı bulundu (p=0,0389). Bununla birlikte hTERT ekspresyonun bazal benzeri histolojik tipte luminal A ve luminal B’ye kıyasla anlamlı derecede yüksek olduğu gösterildi (sırasıyla p=0,0160; p=0,0008).
Sonuç: Çalışmamızın bulguları, meme kanser hastalarında hTERT gen ekspresyonunun sağlıklı örneklere göre anlamlı olarak daha yüksek olduğunu gösterdi. Anormal hTERT gen ekspresyonu kanserojenez veya teşhiste önemli bir rol oynayabilir.
TL;DR: The myrobalan (Terminalia chebula) is one such example that was renowned as the king of medicinal plants in Ayurveda due to its wide range of utilization in herbal decoctions to treat various health disparities as mentioned in this paper .
Abstract: Globalization witnessed changing trends in consumer markets. However, their long-term impacts include lifestyle and dietary changes. Although research in the pharmaceutical and chemical sciences led to the discovery and development of drugs saving millions of lives, their persistent use led to safety and toxicological issues. The plants previously used in Chinese and Ayurveda medicines received attention of the researchers to validate their traditional therapeutic applications. As a result, the reliance of communities on complementary and alternative medicines started to recover in the last few decades. The myrobalan (Terminalia chebula) is one such example that was renowned as the king of medicinal plants in Ayurveda due to its wide range of utilization in herbal decoctions to treat various health disparities. The current review showed phytochemical profile, that includes phenolic acids, casuarinin, chebulagic acid, chebulinic acid, rutin, and corilagin. Phytochemistry is linked with its medicinal applications and several research studies validated its antioxidant, antimicrobial, anti-inflammatory, hypoglycemic, and digestive tonic. The facts presented in the current article are derived from cell culture, animal, and human studies. Moreover, conceptualized framework regarding the effectiveness against cardiovascular disorders, immune dysfunction, cancer insurgence, and neurological disorders is in the limelight of the article. In last, a comprehensive discussion regarding its potential inclusion in the modern-day functional food market and presents its future applications.
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TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.
5,792 citations
Journal Article•
TL;DR: A simple and rapid method for the assay of superoxide dismutase in biological samples is described, which takes advantage of the inhibition of NADH-dependent-nitroblue tetrazolium reduction by the dismut enzyme.
Abstract: A simple and rapid method for the assay of superoxide dismutase in biological samples is described. Present method takes advantage of the inhibition of NADH-dependent-nitroblue tetrazolium reduction by the dismutase. Inhibition of the chromogen formation by superoxide dismutase was linear with increase in enzyme concentrations. The chromogen extract in butanol was stable even up to 48 hr. Superoxide dismutase activity, as assayed by the modified method, was in good agreement with that obtained using other methods.
3,436 citations
TL;DR: It is proposed that the additive and synergistic effects of phytochemicals in fruit and vegetables are responsible for their potent antioxidant and anticancer activities, and that the benefit of a diet rich in Fruit and vegetables is attributed to the complex mixture of phydochemicals present in whole foods.
1,991 citations
TL;DR: The results suggest that tissue GSH-Px can be used as an indicator of animal Se status, but other factors such as age, sex, and dietary vitamin E may have to be considered.
Abstract: Experiments were conducted with male rats to quantitate the relation ship between dietary selenium (Se) intake and the amount of the enzyme glutathione peroxidase (GSH-Px) in erythrocytes and liver. Weanling male rats were fed torula yeast-based diets with 0, 0.05, 0.1, 0.5, 1.0, or 5.0 ppm Se supplemented as sodium selenite. Liver GSH-Px fell to undetectable levels (<1% of that found in the weanling rats) within 24 days in the O ppm Se group; feeding 0.1 ppm Se, or greater, caused liver GSH-Px to increase above that found in the weanling rats. The erythrocyte GSH-Px response to lack of dietary Se was somewhat smaller in magnitude and more gradual; however, only 21% of initial erythrocyte GSH-Px activity remained in the unsupplemented group after 66 days. Increased dietary Se resulted in corresponding increases of erythrocyte GSH-Px activity. Resupplementing with 0.1, 0.5, or 5.0 ppm Se elevated the depressed erythrocyte GSH-Px levels of the deficient rats. Increased dietary Se provided for both faster elevation, and higher maximal GSH-Px activity which in all cases was achieved 60 to 90 days after resupplementation. The results suggest that tissue GSH-Px can be used as an indicator of animal Se status, but other factors such as age, sex, and dietary vitamin E may have to be considered. Lack of GSH-Px in livers of Se-deficient rats may explain the liver necrosis observed when the diet is also deficient in vitamin E and sulfur-containing amino acids. J. Nutr. 104: 580-587,
1,103 citations
TL;DR: 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.
724 citations