-
1.
A Review on Sources and Pharmacological Aspects of Sakuranetin.
Stompor, M
Nutrients. 2020;(2)
Abstract
Sakuranetin belongs to the group of methoxylated flavanones. It is widely distributed in Polyomnia fruticosa and rice, where it acts as a phytoalexin. Other natural sources of this compound are, among others, grass trees, shrubs, flowering plants, cheery, and some herbal drugs, where it has been found in the form of glycosides (mainly sakuranin). Sakuranetin has antiproliferative activity against human cell lines typical for B16BL6 melanoma, esophageal squamous cell carcinoma (ESCC) and colon cancer (Colo 320). Moreover, sakuranetin shows antiviral activity towards human rhinovirus 3 and influenza B virus and was reported to have antioxidant, antimicrobial, antiinflammatory, antiparasitic, antimutagenic, and antiallergic properties. The aim of this review is to present the current status of knowledge of pro-health properties of sakuranetin.
-
2.
Recent Advances in the Development of "Curcumin Inspired" Compounds as New Therapeutic Agents.
Borosky, GL, Laali, KK
Mini reviews in medicinal chemistry. 2020;(15):1543-1558
Abstract
Despite a huge body of research in the past two decades investigating the antioxidant, antiinflammatory, anti-microbial, and anti-carcinogenic properties of curcumin (CUR), a CUR-based antitumor drug is yet to be developed. Lack of success in achieving this goal stems from CUR's unfavorable biophysicochemical features, particularly poor solubility, low bioavailability, and rapid metabolism, coupled with a complex biological profile making it difficult to determine its mechanism of action. A significant body of literature aimed at improving its physicochemical properties through synthesis or by designing delivery methods has been published, and the progress in these areas has been reviewed. The present review aims to summarize recent progress in the synthesis of structurally diverse "curcumin-inspired" compounds along with computational docking and bioassay studies, through which a number of promising analogs have been identified that warrant further study.
-
3.
Berberine reverses epithelial-mesenchymal transition and modulates histone methylation in osteosarcoma cells.
Mishra, R, Nathani, S, Varshney, R, Sircar, D, Roy, P
Molecular biology reports. 2020;(11):8499-8511
Abstract
Osteosarcoma is the most frequently occurring cancer in children as well as young adolescents and the metastatic forms worsen this condition to a further great extent. The metastatic dissemination of cancer cells is often acquired through a process of epithelial-mesenchymal transition (EMT). Since, phytochemicals have attracted intense interest in recent years due to their diverse pharmacological effects, in the present study, we investigated if berberine, a naturally occurring isoquinoline quaternary alkaloid, could modulate the EMT in osteosarcoma cells. Our experimental studies showed that berberine reduced cell viability, colony formation, wound healing ability and migration of osteosarcoma cells. Also, berberine significantly reduced the expression of matrix metalloproteinase (MMP)-2, suggesting its inhibitory action on the matrix metalloproteinases that are required for cancer cell invasion. The significant reduction in the expression of vimentin, N-cadherin, fibronectin and increased expression of E-cadherin further suggested its role in the inhibition of EMT in osteosarcoma cells. The downregulation of H3K27me3, as well as the decreased expression of the histone methyl transferase enzyme EZH2, further substantiated the fact that the plant alkaloid can be used as an epigenetic modulator in the treatment of osteosarcoma. In conclusion, our findings suggest that berberine inhibits proliferation and migration of osteosarcoma cells and most importantly reverses EMT along with modulation of key epigenetic regulators.
-
4.
Salidroside inhibits proliferation, migration and invasion of human pancreatic cancer PANC1 and SW1990 cells through the AKT and ERK signaling pathway.
Yuetong, L, Shangzhu, L, Qinglin, H, Pingping, H
Die Pharmazie. 2020;(8):385-388
Abstract
Salidroside is the main compounds extracted from the Chinese medicine Rhodiola rosea and has many pharmacological effects, including anti-tumor effects. However, the role of salidroside in human pancreatic cancer remains poorly known. Thus, the focus of this study was to evaluate the inhibitory effect of purified salidroside on human pancreatic cancer cells and its underlying molecular mechanisms. PANC1 and SW1990 cells were incubated with various concentrations of salidroside, and CCK-8 assay, colony formation, apoptosis, migration and invasion, western blot were conducted. As a result, it was found that salidroside significantly inhibited pancreatic cancer cells viability, proliferation, migration and invasion, and also induced cell apoptosis. Furthermore, we also detected that salidroside inhibited pancreatic cancer cells by downregulating the AKT and ERK signaling pathways. In conclusion, these findings suggest that salidroside may be a promising candidate for the development of a therapy of human pancreatic cancer.
-
5.
Platelet-rich plasma counteracts detrimental effect of high-glucose concentrations on mesenchymal stem cells from Bichat fat pad.
D'Esposito, V, Lecce, M, Marenzi, G, Cabaro, S, Ambrosio, MR, Sammartino, G, Misso, S, Migliaccio, T, Liguoro, P, Oriente, F, et al
Journal of tissue engineering and regenerative medicine. 2020;(5):701-713
Abstract
Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5-mM glucose (low glucose [LG]) or 25-mM glucose (high glucose [HG]). BFP-MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP-MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high-glucose concentrations impair BFP-MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP.
-
6.
The tRNA pseudouridine synthase TruB1 regulates the maturation of let-7 miRNA.
Kurimoto, R, Chiba, T, Ito, Y, Matsushima, T, Yano, Y, Miyata, K, Yashiro, Y, Suzuki, T, Tomita, K, Asahara, H
The EMBO journal. 2020;(20):e104708
Abstract
Let-7 is an evolutionary conserved microRNA that mediates post-transcriptional gene silencing to regulate a wide range of biological processes, including development, differentiation, and tumor suppression. Let-7 biogenesis is tightly regulated by several RNA-binding proteins, including Lin28A/B, which represses let-7 maturation. To identify new regulators of let-7, we devised a cell-based functional screen of RNA-binding proteins using a let-7 sensor luciferase reporter and identified the tRNA pseudouridine synthase, TruB1. TruB1 enhanced maturation specifically of let-7 family members. Rather than inducing pseudouridylation of the miRNAs, high-throughput sequencing crosslinking immunoprecipitation (HITS-CLIP) and biochemical analyses revealed direct binding between endogenous TruB1 and the stem-loop structure of pri-let-7, which also binds Lin28A/B. TruB1 selectively enhanced the interaction between pri-let-7 and the microprocessor DGCR8, which mediates miRNA maturation. Finally, TruB1 suppressed cell proliferation, which was mediated in part by let-7. Altogether, we reveal an unexpected function for TruB1 in promoting let-7 maturation.
-
7.
Upregulation of amphiregulin by retinoic acid and Wnt signalling promotes liver cancer cell proliferation.
Lin, HH, Peng, YJ, Tsai, MJ, Wu, YY, Tsai, TN, Huang, HH, Shih, YL, Chang, WK, Hsieh, TY
Journal of cellular physiology. 2020;(2):1689-1699
Abstract
Activated hepatic stellate cells promote hepatocellular carcinoma (HCC) progression. Hepatic stellate cells play a key role in retinoid metabolism, and activation of stellate cells increases retinoic acid (RA) in the liver. However, the role of RA in HCC proliferation remains unclear. We aimed to analyse the mechanism of RA in HCC proliferation. Thirty-eight patients who had undergone hepatic resection for HCCs were recruited. Paired non-tumour tissues, adjacent and distal to HCCs, were collected, and the RA levels in the tissues were analysed. The mechanisms of RA and HCC proliferation were assessed in liver cancer cell lines by protein and gene expression analyses. Early recurrence of HCC was significantly higher in patients with a higher RA concentration than in those with a lower RA concentration in tissues adjacent to HCCs (61.1% vs. 20%, p = .010). RA promoted HCC cell proliferation and activated the expression of Amphiregulin, a growth factor in hepatocarcinogenesis. The promoter of Amphiregulin contained the binding sites of the RA receptor, RXRα. Wnt signalling also activated the expression of Amphiregulin, and the RA and Wnt pathways acted synergistically to increase the expression of Amphiregulin. Furthermore, RXRα interacted with β-catenin and then translocated to the nucleus to activate Amphiregulin. An increased RA concentration in the tissues adjacent to the tumour was associated with an early recurrence of HCC. RA activated the expression of Amphiregulin, and then promoted HCC proliferation, which might partly contribute to early recurrence of HCC after hepatic resection.
-
8.
Anticancer Potential of Raddeanin A, a Natural Triterpenoid Isolated from Anemone raddeana Regel.
Naz, I, Ramchandani, S, Khan, MR, Yang, MH, Ahn, KS
Molecules (Basel, Switzerland). 2020;(5)
Abstract
Natural compounds extracted from plants have gained immense importance in the fight against cancer cells due to their lesser toxicity and potential therapeutic effects. Raddeanin A (RA), an oleanane type triterpenoid is a major compound isolated from Anemone raddeana Regel. As an anticancer agent, RA induces apoptosis, cell cycle arrest, inhibits invasion, migration and angiogenesis in malignant cell lines as well as in preclinical models. In this systemic review, the pharmacological effects of RA and its underlying molecular mechanisms were carefully analyzed and potential molecular targets have been highlighted. The apoptotic potential of RA can be mediated through the modulation of Bcl-2, Bax, caspase-3, caspase-8, caspase-9, cytochrome c and poly-ADP ribose polymerase (PARP) cleavage. PI3K/Akt signaling pathway serves as the major molecular target affected by RA. Furthermore, RA can block cell proliferation through inhibition of canonical Wnt/β-catenin signaling pathway in colorectal cancer cells. RA can also alter the activation of NF-κB and STAT3 signaling pathways to suppress invasion and metastasis. RA has also exhibited promising anticancer potential against drug resistant cancer cells and can enhance the anticancer effects of several chemotherapeutic agents. Overall, RA may function as a promising compound in combating cancer, although further in-depth study is required under clinical settings to validate its efficacy in cancer patients.
-
9.
Saffron Crudes and Compounds Restrict MACC1-Dependent Cell Proliferation and Migration of Colorectal Cancer Cells.
Güllü, N, Kobelt, D, Brim, H, Rahman, S, Timm, L, Smith, J, Soleimani, A, Di Marco, S, Bisti, S, Ashktorab, H, et al
Cells. 2020;(8)
Abstract
The high mortality rate of colorectal cancer (CRC) patients is directly associated with metastatic dissemination. However, therapeutic options specifically for metastasis are still limited. We previously identified Metastasis-Associated in Colon Cancer 1 (MACC1) as a major causal metastasis-inducing gene. Numerous studies confirmed its value as a biomarker for metastasis risk. We investigated the inhibitory impact of saffron on MACC1-induced cancer cell growth and motility. Saffron crudes restricted the proliferation and migration of MACC1-expressing CRC cells in a concentration- and MACC1-dependent manner. Saffron delays cell cycle progression at G2/M-phase and does not induce apoptosis. Rescue experiments showed that these effects are reversible. Analysis of active saffron compounds elucidated that crocin was the main compound that reproduced total saffron crudes effects. We showed the interaction of MACC1 with the cancer stem cell (CSC) marker DCLK1, which contributes to metastasis formation in different tumor entities. Saffron extracts reduced DCLK1 with crocin being responsible for this reduction. Saffron's anti-proliferative and anti-migratory effects in MACC1-expressing cells are mediated by crocin through DCLK1 down-regulation. This research is the first identification of saffron-based compounds restricting cancer cell proliferation and motility progression via the novel target MACC1.
-
10.
Resistant starch supplementation increases crypt cell proliferative state in the rectal mucosa of older healthy participants.
Malcomson, FC, Willis, ND, McCallum, I, Xie, L, Ouwehand, AC, Stowell, JD, Kelly, S, Bradburn, DM, Belshaw, NJ, Johnson, IT, et al
The British journal of nutrition. 2020;(4):374-385
-
-
Free full text
-
Abstract
There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.