scholarly journals The Use of Plants’ Natural Products in Breast Cancer: Have We Already Found the New Anticancer Drug?

2021 ◽  
Author(s):  
Isadora de Fátima Braga Magalhães ◽  
Kátia da Silva Calabrese ◽  
Ana Letícia Marinho Figueirêdo ◽  
Ana Lucia Abreu-Silva ◽  
Fernando Almeida-Souza

The importance of a new anticancer drug for breast cancer is well established. Natural compounds that can prevent this disease or be used as an adjuvant treatment associated with conventional drugs could be the solution for this. This chapter is an overview of agents extracted from plants with outstand results in the last six years. Green tea, berberine, thymoquinone and cannabidiol are compounds isolated from medicinal plants. These agents showed action through induction of apoptosis, down regulation of inflammation, epigenetics, hormonal modulation, among other. In vitro effect against cancer cells, in vivo experiments mainly with murine model and clinical trials reassured their efficacy against breast cancer. A protective effect against recurrence cases and chemosensitization to standard drugs was also successful. The use of nanotechnology provided a optimize delivery of these therapeutical molecules. Taken together this information led us to acknowledgement that we do probably have the natural agents for a future adjuvant treatment against breast cancer.

2021 ◽  
Vol 23 (1) ◽  
pp. 129
Author(s):  
Huinan Qu ◽  
Da Qi ◽  
Xinqi Wang ◽  
Yuan Dong ◽  
Qiu Jin ◽  
...  

Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c–MYC–mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co–activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c–MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c–MYC–mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.


1994 ◽  
Vol 12 (11) ◽  
pp. 2460-2470 ◽  
Author(s):  
P E Goss ◽  
K M Gwyn

PURPOSE AND DESIGN: One way to deprive hormone-dependent breast cancer of estrogen is to prevent its synthesis. This is achievable by inhibiting the aromatase cytochrome P-450 (P-450arom) enzyme complex responsible for the ultimate step in estrogen production. A new generation of specific and selective aromatase inhibitors is currently under investigation. The purpose of this review is to outline the preclinical test systems for screening these inhibitors, to summarize the preclinical and clinical data published to date, and to discuss the future application of these inhibitors in the management of breast cancer. RESULTS AND CONCLUSION: Disadvantages to the use of earlier inhibitors are described. In vitro and in vivo experiments that reflect the potency and selectivity of new inhibitors are highlighted. From preliminary clinical trials, these inhibitors appear to have excellent pharmacokinetic profiles and produce few side effects when administered orally. Activity against postmenopausal metastatic breast cancer has been demonstrated for the agents reviewed. They are all now in phase III testing to determine their relative efficacy in this setting. Their application in combination with both hormone therapy and chemotherapy, in premenopausal metastatic disease, and in the adjuvant setting in both premenopausal and postmenopausal women remains to be defined.


2013 ◽  
Vol 1 (39) ◽  
pp. 5288 ◽  
Author(s):  
Hang Xing ◽  
Li Tang ◽  
Xujuan Yang ◽  
Kevin Hwang ◽  
Wendan Wang ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yixiang Huang ◽  
Wenfang Zheng ◽  
Changle Ji ◽  
Xuehui Wang ◽  
Yunhe Yu ◽  
...  

AbstractBreast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3′-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianhui Liu ◽  
Shaoliang Zhu ◽  
Wei Tang ◽  
Qinghua Huang ◽  
Yan Mei ◽  
...  

Abstract Background Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM. Methods Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA. Results Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM. Conclusions Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.


2019 ◽  
pp. 69-82
Author(s):  
Neda Esfandiari ◽  
Amirali Taherian

Background: As cancers, especially breast cancer, have become the most lethal and concerning subject, new methods to promote therapies and achieve better results are strongly essential. Nanotechnology has offered a new approach to advocate the strategies being used and to vanquish their impediments. This article provides a review of the nanomaterials used most recently, mainly in breast cancer, for more effective and specific treatment. Methods: Documents were found in PubMed and Google Scholar using “nanomaterials” and “breast cancer” as the main keywords. Additionally, each individual nanomaterial with “liposomes”, “polymeric NPs”, “dendrimers”, “quantum dots”, “virus like nanoparticles” and “magnetic NPs” keywords were searched and selected after assessments such as publishers, journals impact and their relativities to the subject of the review.  Results: Six frequently used nanoparticles in breast cancer treatment including liposomes, polymeric NPs, dendrimers, VLPs, quantum dots, and magnetic NPs were selected to be discussed in this review. They all showed correlative results such as promoting drug maintenance, hydrophilicity, and accumulation in the tumor site by their specific cell targeting system and high cellular uptake. Each of these NPs has unique properties and disadvantages and therefore many in vitro and in vivo experiments have been carried out. Conclusion: Extensive research into in nanotechnology in medicine, especially in cancer, suggests that nanotechnology could be the dawn of a new era in cancer treatment and imaging.  


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2800-2800
Author(s):  
Christian P. Pallasch ◽  
Janine Schwamb ◽  
Alexandra Schulz ◽  
Svenja Debey ◽  
David Kofler ◽  
...  

Abstract Genome-wide gene expression profiling of chronic lymphocytic leukemia (CLL) cells in comparison to healthy donor CD5-positive B-cells revealed deregulated expression of lipase-associated genes. A set of 19 lipase activity defined genes, e.g. LPL, phospholipases A1, −A2, −C and −D2 family members and other lipase-associated genes were overexpressed in CLL. Recently lipoprotein lipase (LPL) was identified as prognostic factor in CLL. Here we show that the expression of LPL in CLL is induced by B-cell receptor (BCR) stimulus both in mutated and unmutated CLL samples. In native and BCR-stimulated CD5+ healthy B-cells no LPL-expression was detected. Antigenic stimulation via the BCR is thought to be functionally and prognostically relevant in CLL pathogenesis, LPL expression in CLL cells could reflect a permanent BCR-stimulus due to autoantigens including also unmutated IgVH cases. We hypothesized that the overexpression of lipases and especially of LPL reveals a putative therapeutic target by lipase inhibition through the the FDA-approved obesity drug and lipase inhibitor orlistat (tetrahydrolipstatin), which is known to inhibit LPL as well. Treatment of CLL cells with orlistat in vitro revealed significant cytotoxicity and induction of apoptosis in primary CLL cells with an IC50 of 5.48 μM (n=18). In comparison, no significant cytotoxicity was seen with healthy PBMC’s (n=12; p<0.001), even using high doses of orlistat up to 100 μM. Induction of apoptosis induction was observed both in low-risk (ZAP70 negative, n=15) and high-risk (ZAP70-positive, n=10) CLL samples. Orlistat mediated cytotoxicity was slightly decreased by BCR stimulus while additive cytotoxic effects where observed in combination with fludarabine treatment. Susceptibility to orlistat treatment was not dependent on Binet stage. In summary, we provide in vitro data for a criticial role of fatty acid metabolism in CLL pathogenesis and suggest a therapeutic potential of the lipase inhibitor orlistat. No severe systemic side effects of orlistat have been observed in several animal models and in the current clinical application as anti-obesity drug. Orlistat seems to be a promising candidate for an anti-leukemic therapy in CLL, ongoing in vivo experiments applying the TCL1 mouse model will further elucidate the therapeutic potential of orlistat.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Jun Liu ◽  
Feng Xu ◽  
Jie Li ◽  
Hongchuan Jiang

Abstract Objectives: The high mortality of breast cancer (BC) is associated with the strong metastatic properties of primary breast tumor cells. The present study was conducted in order to clarify the effect of Cosmc on the growth and metastasis of BC cell lines of different molecular types, which may be implicated in the regulation of Tn and T glycans. Methods: BC cell lines with different molecular types were transduced with shRNA targeting Cosmc or, Cosmc overexpression plasmid in order to explore the role of Cosmc in cell proliferation, migration, invasion, and apoptosis. The protein levels of Tn, T, Cosmc, proliferation-related factors (Ki67 and PCNA) and apoptosis-related factors (Bax and Bad) in BC cell lines were determined by Western blot analyses. Finally, the role of Cosmc was substantiated through in vivo experiments. Results: Cosmc was down-regulated in different subtypes of BC cell lines compared with normal control cells. Overexpression of Cosmc suppressed the proliferation, migration, and invasion, yet promoted the apoptosis of BC cells, as reflected by in vitro experiments. Additionally, in vivo tumor xenografts in nude mice showed that ectopic overexpression of Cosmc inhibited the tumor growth of BC cells. Consequently, the levels of proliferation-related factors and Tn antigen were decreased, while those of apoptosis-related factors and T antigen were increased in BC cells. This observation was confirmed in vivo in xenograft tumors. Conclusion: Collectively, up-regulation of Cosmc potentially impedes BC growth and metastasis by modulating the balance between Tn and T glycans.


Polymers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1307 ◽  
Author(s):  
Angel Hernandez-Martinez ◽  
Gustavo Molina ◽  
Rodrigo Esparza ◽  
Ángel Luis Rodríguez ◽  
Martha Cruz-Soto ◽  
...  

Strength and biocompatibility of composite materials (using a polymer matrix) are used in medicine for various devices such as prostheses and marker clips (biomarkers). Marker clips indicate the site of a lesion in the body, specifically for breast cancer diagnosis or treatment. In general, marker clips are made of steel or titanium, but lately, materials containing biodegradable polymers had been proposed. Our hypothesis is that a copolymer of polylactic acid and poly(ε-caprolactone) (PLA-PCL) could be used as marker clip material. After evaluating different polymer rates performance, metallic nanoparticles (NPs) were included to enhance the stability of the best copolymer and a marker clip prototype was proposed. Characterization of nanoparticles was made by dynamic light scattering (DLS), X-ray diffraction (XRD) and magnetic measurements. Mechanical, thermal and radiopacity properties were evaluated for composites formulation. In vitro, radiopaque experiments showed that BM-2 composite had the best performance. In vivo experiments showed that, after five months, the marker clip prototype maintained its shape, visibility and contrast properties. In consequence, a novel formulation of composite (PLA-PCL/metallic nanoparticles) is suitable for further studies as an alternative material for marker clips for breast cancer lesions.


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