scholarly journals In vitro and in vivo studies on stilbene analogs as potential treatment agents for colon cancer

2010 ◽  
Vol 45 (9) ◽  
pp. 3702-3708 ◽  
Author(s):  
Shiby Paul ◽  
Cassia S. Mizuno ◽  
Hong Jin Lee ◽  
Xi Zheng ◽  
Sarah Chajkowisk ◽  
...  
2021 ◽  
Author(s):  
JUNDONG WANG ◽  
TIANHAO LI ◽  
CHAOCHI YUE ◽  
SEN ZHONG ◽  
XIANGDONG YANG ◽  
...  

Abstract BackgroundThe problems associated with poor water solubility of anticancer drugs are one of the most important challenges in achieving effective cancer therapy. The present study was designed to evaluate the effect of Scutellarein on human colon cancer cells in vitro by using a target αvβ-3 novel Scutellarein (Scu)-loaded niosome nanoparticle (β-CD-CL-Scu-cRGD).Resultsβ-CD-CL-Scu-cRGD has a diameter of 140.2nm and a zeta potential of -11.3 mV with a constant physicochemical stability. The MTT assay showed both Scu and β-CD-CL-Scu-cRGD caused a decrease in cell proliferation and viability of HT29, but β-CD-CL-Scu-cRGD showed better activity in vitro. Colony formation assay and flow cytometry assay showed that β-CD-CL-Scu-cRGD has a better effect on cell proliferation and apoptosis.ConclusionsAlthough further in vivo studies are necessary, our results suggested that β-CD-CL-Scu-cRGD could be an outstanding carrier to deliver Scu for potential therapeutic approaches into colon cancer.


2021 ◽  
Author(s):  
Yi Li ◽  
Chunli Zhang ◽  
Xiaohan Ma ◽  
Liuqing Yang ◽  
Huijun Ren

Abstract Radix Puerariae (RP), a dry root of the Pueraria lobata (Willd.) Ohwi, is used to treat a variety of diseases, including cancer. Several in vitro and in vivo studies have demonstrated the efficacy of RP in the treatment of colon cancer (CC). However, the biological mechanism of RP in the treatment of colon cancer remains unclear. In this study, the active component of RP and its potential molecular mechanism against CC were studied by network pharmacology and enrichment analysis. The methods adopted included screening of active ingredients of Chinese medicine, prediction of target genes of Chinese medicine and disease, construction of protein interaction network, and GO and KEGG Enrichment Analysis. Finally, the results of network pharmacology were further validated by molecular docking experiments and cell experiments. 8 active constituents and 14 potential protein targets were screened from RP, including EGFR, JAK2 and SRC. The biological mechanism of RP against CC was analyzed by studying the relationship between active components, targets, and enrichment pathway. This provides a basis for understanding the clinical application of RP in CC.


2018 ◽  
Vol 9 (1) ◽  
pp. 190-199 ◽  
Author(s):  
Geet P. Asnani ◽  
Chandrakant R. Kokare

AbstractThe aim of this study was to formulate a novel dual crosslinked hydrogel bead using Portulaca mucilage for colon-targeted delivery of 5-fluorouracil (5-FU) and evaluate its safety, specificity and efficacy. The ionotropic gelation technique was employed to prepare the hydrogel beads of Portulaca mucilage. For this, the mucilage was initially crosslinked with alginate and calcium ions. Epichlorohydrin was employed as a crosslinker in the second crosslinking step. The formulation was subjected to in vitro and in vivo studies to evaluate morphology, size, cytotoxicity, and organ distribution. Human HT-29 colon cancer cell-line was used for in vitro assays and in vivo studies were performed in Wistar rats to assess the usefulness and effectiveness of the formulation for colon cancer therapy. Microsphere sizes ranged from 930 to 977μm and possessed a high level of drug encapsulation efficiency (ca. 78% w/w). Compared with 5-FU solution (Tmax = 1.2 h, mean resident time: MRT = 3.3h) the dual crosslinked Portulaca microspheres exhibited sustained drug release after oral administration to rats (Tmax = 16h, MRT = 14h). The relative bioavailability of 5-FU solution and the microspheres were 100 and 93.6% respectively. Tissue distribution studies indicated high concentration of 5-FU in colon. In-vitro anticancer assay demonstrated IC50 value of 11.50 μg/ml against HT-29 colon cancer cell line. The epichlorohydrin cross-linked Portulaca microspheres prepared in this study provided sustained release of 5-FU up to 16h in the colonic region and enhanced the antitumor activity of the neoplastic drug. The formulation is hence an ideal carrier system for colon-targeted drug delivery.


2010 ◽  
Vol 21 (6) ◽  
pp. 538-543 ◽  
Author(s):  
Chiu-Li Yeh ◽  
Man-Hui Pai ◽  
Cheng-Chung Li ◽  
Yu-Ling Tsai ◽  
Sung-Ling Yeh

2018 ◽  
Vol 8 (5) ◽  
pp. 1226-1237 ◽  
Author(s):  
Mahboubeh Rezazadeh ◽  
Niloofar Jafari ◽  
Vajihe Akbari ◽  
Marjan Amirian ◽  
Majid Tabbakhian ◽  
...  

2021 ◽  
Author(s):  
Karolina Beton ◽  
Piotr Wysocki ◽  
Beata Brozek-Pluska

One of the most important areas of medical science is oncology, which is responsible for both the diagnostics and treatment of cancer diseases. Simultaneously one of the main challenges of oncology is the development of modern drugs effective in the fight against cancer. Statins are a group of biologically active compounds with the activity of 3-hydroxy-3-methyl glutaryl-CoA reductase inhibitors, an enzyme catalyzing the reduction of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) to mevalonic acid. By acting on this enzyme, statins inhibit the endogenous cholesterol synthesis which in turn causes the reduction of its systemic concentrations. However, in vitro and in vivo studies confirm also the cytostatic and cytotoxic effects of statins against various types of cancer cells including colon cancer. In the presented studies the influence of mevastatin on cancerous colon cells CaCo-2 by Raman spectroscopy and imaging is discussed and compared with biochemistry characteristic for normal colon cells CCD-18Co. Based on vibrational features of colon cells: normal cells CCD-18Co, cancerous cells CaCo-2 and cancerous cells CaCo-2 treated by mevastatin in different concentrations and incubation times we have confirm the influence of this statin on biochemistry composition of cancerous human colon cells. Moreover, the spectroscopic results for colon normal cells and cancerous cells based on data typical for nucleic acids, proteins, lipids have been compared. The cytotoxisity of mevastatin was determined by using XTT tests.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 454-454
Author(s):  
Wu Zhang ◽  
Armin Gerger ◽  
Melissa Janae Labonte ◽  
Dongyun Yang ◽  
Pierre Oliver Bohanes ◽  
...  

454 Background: Recent evidence suggests that Lemur Tyrosine Kinase 3 (LMTK3) activates estrogen receptor alpha (ERα) transcriptional activity in breast cancer. The mutant variants of two single nucleotide polymorphisms (SNPs) in LMTK3 (rs8108419 and rs9989661) were independently associated with reduced time to tumor recurrence (TTR), suggesting these SNPs were functionally significant. In colon cancer (CC), ERβ expression has been shown to be predominant with low levels of ERα also expressed. ERα stimulates cell proliferation, while ERβ negatively regulates the estrogen-dependent activity of ERα. Based on these previous findings, we hypothesized that LMTK3 rs808419 and rs9989661 may predict TTR in stage II and III CC. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 yrs (range 22–78 yrs)) with stage II (105 pts) or III (129 pts) CC at the University of Southern California. The median follow-up was 4.4 years. LMTK3 rs8108419 and rs9989661 were determined by PCR-RFLP. The primary endpoint of the study was TTR. This study was conducted adhering to the reporting recommendations for tumor marker prognostic studies (REMARK). Results: The minor allele of LMTK3 rs9989661 (C; frequency=30.5%) showed significantly longer median TTR (5.9 vs 12.2+ yrs; HR: 0.41, 95%CI: 0.15-1.18, log-rank p=0.086; univariate analysis) in female CC patients. After Cox proportional hazards model adjustment for stage and type of adjuvant chemotherapy, this result remained significant (HR: 0.25, 95%CI: 0.077-0.778, Wald test p=0.017). No significant association was found between TTR and LMTK3 rs9989661 in men and rs8108419 in both genders. Conclusions: This is the first report demonstrating LMTK3 rs9989661 associations with gender-related TTR in CC. We hypothesize that there is an ERα-dependent loop mechanism with higher estrogen levels in females exerting the effect on ERβ. Larger prospective trials are warranted to confirm these findings, and in vitro and in vivo studies are needed to identify the underlying biological mechanism.


2021 ◽  
Vol 22 (2) ◽  
pp. 716
Author(s):  
Osman Ali ◽  
Mazen Tolaymat ◽  
Shien Hu ◽  
Guofeng Xie ◽  
Jean-Pierre Raufman

Despite great advances in our understanding of the pathobiology of colorectal cancer and the genetic and environmental factors that mitigate its onset and progression, a paucity of effective treatments persists. The five-year survival for advanced, stage IV disease remains substantially less than 20%. This review examines a relatively untapped reservoir of potential therapies to target muscarinic receptor expression, activation, and signaling in colorectal cancer. Most colorectal cancers overexpress M3 muscarinic receptors (M3R), and both in vitro and in vivo studies have shown that activating these receptors stimulates cellular programs that result in colon cancer growth, survival, and spread. In vivo studies using mouse models of intestinal neoplasia have shown that using either genetic or pharmacological approaches to block M3R expression and activation, respectively, attenuates the development and progression of colon cancer. Moreover, both in vitro and in vivo studies have shown that blocking the activity of matrix metalloproteinases (MMPs) that are induced selectively by M3R activation, i.e., MMP1 and MMP7, also impedes colon cancer growth and progression. Nonetheless, the widespread expression of muscarinic receptors and MMPs and their importance for many cellular functions raises important concerns about off-target effects and the safety of employing similar strategies in humans. As we highlight in this review, highly selective approaches can overcome these obstacles and permit clinicians to exploit the reliance of colon cancer cells on muscarinic receptors and their downstream signal transduction pathways for therapeutic purposes.


2020 ◽  
Vol 21 (6) ◽  
Author(s):  
Ghoson Daba ◽  
Waill Elkhateeb ◽  
Asmaa Negm ELDien ◽  
Eman Fadl ◽  
Ali Elhagrasi ◽  
...  

Abstract. Daba GM, Elkhateeb WA, El-Dien AN, Ahmed EF, El Hagrassi AM Fayad W, Wen TC. 2020. Therapeutic potentials of n-hexane extracts of the three medicinal mushrooms regarding their anti-colon cancer, antioxidant, and hypocholesterolemic capabilities. Biodiversitas 21: 2437-2445. Evaluating in vitro biological activities of the medicinal mushrooms Hericium erinaceus, Metacordyceps neogunnii, and Dictyophora indusiata n-hexane extracts revealed their capabilities as promising therapeutic sources. By assessing their DPPH radical scavenging activities, D. indusiata extract exhibited the highest antioxidant activity (87.8±1.2%) followed by H. erinaceus, then M. neogunnii 84.9±1.6%, and 77.3±1.3%, respectively. On the other hand, M. neogunnii extract exerted promising anti-colon cancer (68.6±3.6% cytotoxicity) against HCT116 human colon cancer cell lines at concentration 100 μg/mL, whereas H. erinaceus and D. indusiata extracts exhibited weaker cytotoxic effects (18.3±1.7%, and 19.3±3.2%, respectively) using the same concentration. Investigating cholesterol reduction activities (CRA%) of the extracts revealed that activity depends on both extract concentration and incubation period. After 96 h of incubation at room temperature, all extracts exerted potent in vitro hypocholesterolemic activities (100±0% reduction in cholesterol concentration). Performing GC-Ms analyses on the extracts revealed presence of 22 compounds in D. indusiata extract, while 29 compounds were detected in M. neogunnii extract, and 33 in H. erinaceus extract. Most of compounds were esters of fatty acids. Results in this study encourage using these mushrooms as functional foods, and highlight the need for conducting further in vivo studies to support their use in pharmaceutical industry.


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