In Vivo Anti Cancer Potential of Pyrogallol in Murine Model of Colon Cancer

The search for effective methods of cancer treatment and prevention has been a continuous effort since the disease was discovered. Recently, there has been increasing interest in exploring plants and fruits for molecules that may have potential as either adjuvants or as chemopreventive agents against cancer. One of the promising compounds under extensive research is nobiletin (NOB), a polymethoxyflavone (PMF) extracted exclusively from citrus peel. Not only does nobiletin itself exhibit anti-cancer properties, but its derivatives are also promising chemopreventive agents; examples of derivatives with anti-cancer activity include 3′-demethylnobiletin (3′-DMN), 4′-demethylnobiletin (4′-DMN), 3′,4′-didemethylnobiletin (3′,4′-DMN) and 5-demethylnobiletin (5-DMN). In vitro studies have demonstrated differential efficacies and mechanisms of NOB and its derivatives in inhibiting and killing of colon cancer cells. The chemopreventive potential of NOB has also been well demonstrated in several in vivo colon carcinogenesis animal models. NOB and its derivatives target multiple pathways in cancer progression and inhibit several of the hallmark features of colorectal cancer (CRC) pathophysiology, including arresting the cell cycle, inhibiting cell proliferation, inducing apoptosis, preventing tumour formation, reducing inflammatory effects and limiting angiogenesis. However, these substances have low oral bioavailability that limits their clinical utility, hence there have been numerous efforts exploring better drug delivery strategies for NOB and these are part of this review. We also reviewed data related to patents involving NOB to illustrate the extensiveness of each research area and its direction of commercialisation. Furthermore, this review also provides suggested directions for future research to advance NOB as the next promising candidate in CRC chemoprevention.

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In-vivo anti colorectal cancer activity of Coldenia procumbens on DMH induced colon cancer in wistar rats

International Journal of Research in Phytochemistry and Pharmacology ◽

10.26452/ijrpp.v9i2.1196 ◽

2020 ◽

Vol 9 (2) ◽

pp. 14-22

Author(s):

Ramachandran K ◽

Venketnarayanan R ◽

Rajesh Yadav ◽

Suresh R ◽

Sumitra Devkota

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Wistar Rats ◽

The United States ◽

Colorectal Polyps ◽

Men And Women ◽

Toxicological Profile ◽

Anti Cancer ◽

Cancer Activity

Colorectal cancer is the second leading cause of cancer death in the United States for both men and women. The rate of colon cancer incidence was low in India but is presently increasing; out of 3.5 million cancer cases, 35,000 have colon cancer. Polyps which are the small growths in the colon are most often benign, even though some have the potentiality to become cancerous. Up to two-thirds of the colorectal polyps are pre-malignant and they are linked with a risk of colorectal cancer. About 60% of currently used anti-cancer agents are derived from a natural source (i.e. plants). In our study anti-cancer potential of the extract of Coldenia procumbens was studied and the synthesis of the anti-cancer moiety has been done. With the findings, it can be concluded that the plant Coldenia procumbens Linn and possess anti colorectal cancer activity. Before the clinical usage of extract, through toxicological profile has to be determined on the crude extracts as well as on isolated compounds to confirm the safety of the drug.

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Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

Cellular Physiology and Biochemistry ◽

10.1159/000493960 ◽

2018 ◽

Vol 50 (1) ◽

pp. 79-91 ◽

Cited By ~ 7

Author(s):

Wei Yan ◽

Mingyue Tao ◽

Baofei Jiang ◽

Mengchu Yao ◽

Yali Jun ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Targeted Delivery ◽

Glycoprotein P ◽

Anti Cancer ◽

Lovo Cells ◽

Si Rna ◽

Cancer Activity

Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings.

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In vivo anti-carcinogenic property of a formulated citrus peel extract

Functional Foods in Health and Disease ◽

10.31989/ffhd.v4i3.21 ◽

2014 ◽

Vol 4 (3) ◽

pp. 120 ◽

Cited By ~ 4

Author(s):

Michiko Suzawa ◽

Limin Guo ◽

Min-Hsiung Pan ◽

Chi-Tang Ho ◽

Shiming Li

Keyword(s):

Prostate Cancer ◽

Colon Cancer ◽

Skin Cancer ◽

Model Systems ◽

Therapeutic Effects ◽

Citrus Peel ◽

Anti Cancer ◽

Medical Foods ◽

Cancer Côlon

Background: Cancer is one of the two leading fatal diseases humans face. Synthesized drugs available for cancer intervention have many limitations in applications and effectiveness and are often associated with serious of side effects, which can further damage the patients’ quality of life. Recently, the development of natural-product-based and therapeutically sound anti-cancer agents have gained popularity in the fields of functional and medical foods, which may exhibit advantages of minimal toxicity and multiple active molecular components. Citrus peel or its extract has been reported to have potent pharmacological activities and health benefits because of abundant flavonoids present in citrus fruits, particularly in the peels. Results: The results of these studies demonstrated the efficacy of Gold Lotion (GL), an extract of multiple varieties of citrus peels that contains abundant flavonoids, including a high percentage of polymethoxylflavones (PMFs), which can protect against skin cancer, colon cancer, and prostate cancer in mice. These results are clearly promising and warrant a human trial with GL in future studies. Summary: Briefly, these data have demonstrated that GL is efficacious in preventing and treating cancer in several model systems. This review summarizes the results of currently available data regarding the in vivo anti-cancer activity of GL, and identifies opportunities for subsequent human clinical trials to assess preventive and therapeutic effects in the near future.Keywords: gold lotion, citrus peel extracts, skin cancer, colon cancer, prostate cancer

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Appraisal of the anti-cancer potential of probiotic Pediococcus pentosaceus GS4 against colon cancer: in vitro and in vivo approaches

Journal of Functional Foods ◽

10.1016/j.jff.2016.02.032 ◽

2016 ◽

Vol 23 ◽

pp. 66-79 ◽

Cited By ~ 23

Author(s):

Vinay Dubey ◽

Asit Ranjan Ghosh ◽

Kausik Bishayee ◽

Anisur Rahman Khuda-Bukhsh

Keyword(s):

Colon Cancer ◽

Pediococcus Pentosaceus ◽

Anti Cancer

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Essential Oil Compound, Patchouli Alcohol, Represses Tumor Formation in Vivo and Causes G1 Arrest by Downregulating β-catenin Transcriptional Activity in Colon Cancer Cells (FS13-02-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz030.fs13-02-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Jihye Lee ◽

Seong-Ho Lee

Keyword(s):

Colon Cancer ◽

Cancer Cell ◽

Transcriptional Activity ◽

G1 Arrest ◽

Patchouli Alcohol ◽

Colon Cancer Cell Lines ◽

Gene Assay ◽

Anti Cancer ◽

Reliable Mechanism

Abstract Objectives Patchouli alcohol is one of the abundant compounds isolated from essential oil of Pogostemon cablin and shows anti-inflammatory, anti-obese and anti-cancer activities. The current study was designed to investigate if treatment of patchouli alcohol exhibits tumor suppressive activity in colon cancer mouse model and define a reliable mechanism using in vitro culture system using colon cancer cell lines. Methods Twenty seven 4-week old Apcmin/+ mice were assigned into one of three groups (n = 9) and patchouli alcohol (0, 25 or 50 mg/kg body weight) was orally administered three times a week for six weeks before/after treatment of dextran sulfate sodium (DSS). At age 10-week old, all animals were sacrificed, colon and small intestines were collected, and the number and size of tumors were counted and measured. Human colon cancer cell lines (HT-29, Lovo and Caco-2) were treated with different concentration of patchouli alcohol for 48 hours. And cell cycle distribution was measured using FACS and luciferase reporter gene assay was performed to elucidate reliable mechanism of anti-cancer activity. Results In vivo study indicated that the number of tumor and tumor load was significantly decreased in a dose-dependent manner by administering patchouli alcohol (25 and 50 mg/kg body weight). Treatment of 100 µM patchouli alcohol led to G1 arrest with decreased cell proliferation. Reporter gene assay showed decreased transcriptional activity of β-catenin in patchouli alcohol-treated cells. Conclusions Patchouli alcohol prevents formation of adenoma polyps by repressing cancer cell growth/division via downregulating transcriptional activity of β-catenin in colon cancer model. Funding Sources NIFA Hatch grant. Supporting Tables, Images and/or Graphs

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Standardized Astragalus Mongholicus Bunge-Curcuma Aromatica Salisb. Extract Efficiently Suppresses Colon Cancer Progression Through Gut Microbiota Modification in CT26-Bearing Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2021.714322 ◽

2021 ◽

Vol 12 ◽

Author(s):

Junfei Gu ◽

Ruolan Sun ◽

Qiaohan Wang ◽

Fuyan Liu ◽

Decai Tang ◽

...

Keyword(s):

Colon Cancer ◽

Gut Microbiota ◽

Cancer Progression ◽

Fatty Acid Content ◽

Intestinal Barrier ◽

Mucosal Barrier ◽

Drug Pair ◽

Anti Cancer ◽

Colon Cancer Progression

Altered gut microbiota and a damaged colon mucosal barrier have been implicated in the development of colon cancer. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (ACE) is a common herbal drug pair that widely used clinically to treat cancer. However, whether the anti-cancer effect of ACE is related to gut microbiota remains unclear yet. We standardized ACE and investigated the effects of ACE on tumour suppression and analyze the related mechanisms on gut microbiota in CT26 colon cancer-bearing mice in the present study. Firstly, four flavonoids (calycosin-7-glucoside, ononin, calycosin, formononetin) and three astragalosides (astragaloside A, astragaloside II, astragaloside I) riched in Astragalus mongholicus Bunge, three curcumins (bisdemethoxycurcumin, demethoxycurcumin, curcumin) and four essential oils (curdione, curzerene, germacrone and β-elemene) from Curcuma aromatica Salisb., in concentrations from 0.08 to 2.07 mg/g, were examined in ACE. Then the results in vivo studies indicated that ACE inhibited solid tumours, liver and spleen metastases of colon cancer while simultaneously reducing pathological tissue damage. Additionally, ACE regulated gut microbiota dysbiosis and the short chain fatty acid content in the gut, repaired intestinal barrier damage. ACE treatment suppressed the overgrowth of conditional pathogenic gut bacteria, including Escherichia-Shigella, Streptococcus and Enterococcus, while the probiotic gut microbiota like Lactobacillus, Roseburia, Prevotellaceae_UCG-001 and Mucispirillum were increased. More interestingly, the content level of SCFAs such as propionic acid and butyric acid was increased after ACE administration, which further mediates intestinal SDF-1/CXCR4 signalling pathway to repair the integrity of the intestinal barrier, decrease Cyclin D1 and C-myc expressions, eventually suppress the tumor the growth and metastasis of colon cancer. To sum up, the present study demonstrated that ACE could efficiently suppress colon cancer progression through gut microbiota modification, which may provide a new explanation of the mechanism of ACE against colon cancer.

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Prevotella Contributing to the Individual Respons E of e of FOLFOX in Colon Cancer

10.21203/rs.3.rs-142740/v1 ◽

2021 ◽

Author(s):

Fengguo Xu ◽

Xiaoying Hou ◽

Weihua Chu ◽

Hongzhi Du ◽

Yiqiao Gao ◽

...

Keyword(s):

Colon Cancer ◽

Predictive Biomarkers ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Individual Response ◽

Sequencing Analysis ◽

Anti Cancer ◽

Underlying Mechanisms ◽

The Individual

Abstract While FOLFOX has been the preferred chemotherapeutic strategy in colon cancer treatment, the limited response rate has seriously restricted its application in clinic. The underlying mechanisms of the individual response of FOLFOX remain to be elucidated. In this study, pharmacomicrobiomics integrated with pharmacometabolomics was applied to disentangle the key role of specific gut bacteria and microbiota derived metabolites involved. As a result , significant variation of chemotherapy efficacy was observed in tumor bearing mice after FOLFOX administration. 16S rRNA gene sequencing analysis revealed the relative abundance of Staphylococcus , Jeotgalicoccus , Sphingomonas significantly increased in the FOLFOX sensitive group, whereas Prevotella was higher in the non sensitive individuals . Meanwhile, verification study o n FOLFOX combined with bacteria colonization indicates that Prevotella could attenuate the anti cancer efficacy of FOLFOX in vivo . Furthermore, gut derived metabolite 3-Oxocholic acid (3-Oxo) identified by metabolomics approach was confirmed to associate with Prevotella in fecal samples. In addition, preliminary functional exploration suggested that 3-Oxo could reverse the anti cancer effect of FOLFOX and promote malignant progression Taken together, integrated pharmacomicrobiomics and pharmacometabolomics revealed that Prevotella and related metabolite 3-Oxo may be responsible for individualized FOLFOX efficacy, which provides novel predictive biomarkers for FOLFOX precise medicine as well as targets for colon cancer therapy.

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