A Review of Anti-Cancer and Related Properties of Lichen-Extracts and Metabolites

2021 ◽  
Vol 21 ◽  
Author(s):  
Ankita H. Tripathi ◽  
Nidhi Negi ◽  
Rekha Gahtori ◽  
Amrita Kumari ◽  
Penny Joshi ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Multiple Drug Resistance ◽  
Usnic Acid ◽  
Multiple Drug ◽  
Proliferative Potential ◽  
Mesenchymal Transition ◽  
Anti Cancer ◽  
Lichen Substances ◽  
Lichen Metabolites ◽  
Anti Inflammatory

Background: Lichens are a composite consortium of fungus and alga. The symbiotic organisms are naturally equipped with distinct characteristics as compared to constituting organisms separately. Lichens due to their peculiar anatomy and physiology, are the reservoir of more than 600 unique secondary metabolites, also known as ‘lichen substances’. Since ancient times, many ethnic groups from various parts of the world had knowledge about the applications of lichens as major provenance of food/fodder, medicine, dyes, spices, perfumes, etc. Lichen substances have shown impressive antioxidant, antimicrobial, antiviral, antitumor, and anti-inflammatory activities under experimental conditions. Usnic acid, a well-known metabolite, found in several species of lichens, possesses potent antioxidant and anti-inflammatory activities. It also has significant anti-proliferative potential as revealed through testing in different cancer cell lines. Atranorin, Lecanoric acid, Norstictic acid, Lobaric acid, Stictic acid, Ramalin, Gyrophoric acid, Salazinic acid, Protolichesterinic, and Fumarprotocetraric acid are some of the other purified lichen metabolites with potent anti-cancer activities. Objective: This study presents an overview of lichen derived extracts/compounds augmenting the anti-cancer (related) properties. Method: The review comprehends different studies (in vivo and in vitro) backing up the possibility of lichen extracts and metabolites towards their use as antioxidant, anti-proliferative, anti-inflammatory and EMT-inhibiting agents. Results: The review focuses on anti-cancer and related properties of lichen extracts and metabolites that include their anti-oxidative, anti-inflammatory, anti-proliferative and pro-apoptotic, cancer stemness reduction, activities and, the potential of inhibition of cancer-associated Epithelial-mesenchymal transition (EMT) that is responsible for multiple drug-resistance and metastasis of cancer cells in a large proportion of cases. Conclusion: Lichens can be the repertoire of a plethora of lichen metabolites with putative bioactive potential, which is needed to be explored in order to find out novel anti-cancer drugs.

scholarly journals TGF-β Signaling and Resistance to Cancer Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Maoduo Zhang ◽  
Ying Yi Zhang ◽  
Yongze Chen ◽  
Jia Wang ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Multiple Drug Resistance ◽  
Transforming Growth Factor Β ◽  
Multiple Drug ◽  
Cancer Resistance ◽  
Mesenchymal Transition ◽  
Key Factor ◽  
Cancer Multiple

The transforming growth factor β (TGF-β) pathway, which is well studied for its ability to inhibit cell proliferation in early stages of tumorigenesis while promoting epithelial-mesenchymal transition and invasion in advanced cancer, is considered to act as a double-edged sword in cancer. Multiple inhibitors have been developed to target TGF-β signaling, but results from clinical trials were inconsistent, suggesting that the functions of TGF-β in human cancers are not yet fully explored. Multiple drug resistance is a major challenge in cancer therapy; emerging evidence indicates that TGF-β signaling may be a key factor in cancer resistance to chemotherapy, targeted therapy and immunotherapy. Finally, combining anti-TGF-β therapy with other cancer therapy is an attractive venue to be explored for the treatment of therapy-resistant cancer.

scholarly journals Verteporfin can Reverse the Paclitaxel Resistance Induced by YAP Over-Expression in HCT-8/T Cells without Photoactivation through Inhibiting YAP Expression

2016 ◽  
Vol 39 (2) ◽  
pp. 481-490 ◽  
Author(s):  
Wang Pan ◽  
Qian Wang ◽  
Yi Zhang ◽  
Naishu Zhang ◽  
Jiamin Qin ◽  
...  
Keyword(s):  
T Cells ◽  
Combination Therapy ◽  
Multiple Drug Resistance ◽  
Protein Detection ◽  
Multiple Drug ◽  
Over Expression ◽  
Anti Cancer ◽  
The Relationship ◽  
Proliferation And Invasion ◽  
Main Factor

Background/Aims: Paclitaxel (PTX) is one of the most effective anti-cancer drugs. However, multiple drug resistance is still the main factor that hinders the effective treatment of cancer with PTX. Several factors including YAP over-expression can cause PTX resistance. In this study, we aimed to verify the role YAP plays in PTX resistance, explore the reversal of PTX resistance by verteporfin (VP) and investigate the effect of combination therapy of PTX and VP on the PTX resistant colon cancer cells (HCT-8/T). Methods: To study the relationship between YAP and PTX resistance, a stable YAP-over-expression or YAP silencing cell line was generated by transfected with YAP-plasmids or siYAP-RNA. WST-1 assay was performed to detect the cytotoxicity of PTX on HCT-8 and HCT-8/T cells. Clone formation assay and Transwell assay was preformed to determine the cell proliferation and invasion ability respectively. Immunofluorescence and Western blot analysis was performed for protein detection. Results: YAP was stronger expressed in HCT-8/T than in HCT-8, and PTX resistance was positively correlated with the level of YAP expression. VP, a strongly YAP inhibitor, could reduce the PTX resistance on HCT-8/T cells without light activation by inhibiting YAP. Beside, VP and PTX combination therapy showed synergism on inhibition of YAP and cytotoxicity to HCT-8/T. Moreover, verteporfin and PTX combination therapy affect the invasion and colony formation ability and induce apoptosis of HCT-8/T cells. Conclusions: VP can reverse the PTX resistance induced by YAP over-expression in HCT-8/T cells without photoactivation through inhibiting YAP expression.

scholarly journals miR-942-5p Inhibits Proliferation, Metastasis, and Epithelial-Mesenchymal Transition in Colorectal Cancer by Targeting CCBE1

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Lin Zhou ◽  
Qing Chen ◽  
Jie Wu ◽  
Jian Yang ◽  
Huancai Yin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Opposite Effect ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Proliferative Potential ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Clinical Biomarker

Although colorectal cancer (CRC) is common, there is a paucity of information regarding its molecular pathogenesis. Studies have shown that miRNAs play pivotal roles in the development and progression of CRC. There is a need to further investigate the biological functions of miRNAs in CRC. In particular, it has been reported that miR-942-5p exhibits tumor-suppressive properties. Thus, we analyzed the functional significance of miR-942-5p in CRC and the underlying molecular mechanisms. We found that miR-942-5p was downregulated in CRC tissues and cells. Cell Counting Kit-8, EdU, and colony formation assays revealed that the overexpression of miR-942-5p by mimics inhibited the proliferation of CRC cells. Use of the miR-942-5p inhibitor effectively enhanced the proliferative potential of CRC cells. Further, in vivo xenograft experiments confirmed these results. Increased expression of miR-942-5p suppressed the invasion, migration, and epithelial-mesenchymal transition of CRC cell lines, while decreased miR-942-5p expression had the opposite effect. CCBE1, a secretory molecule for lymphangiogenesis, was established as a downstream target of miR-942-5p, and its expression was inversely correlated with the expression of miR-942-5p in CRC cells. Additionally, cotransfection of the miR-942-5p inhibitor with si-CCBE1 into CRC cells reversed the effects induced by miR-942-5p overexpression. In conclusion, we confirmed that miR-942-5p exerts oncogenic actions in CRC by targeting CCBE1 and identified miR-942-5p as a potential clinical biomarker for CRC diagnosis and therapy.

scholarly journals The Synergistic Anti-Cancer Effects of NVP-BEZ235 and Regorafenib in Hepatocellular Carcinoma

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2454
Author(s):  
Cheng-Chan Yu ◽  
Sung-Ying Huang ◽  
Shu-Fang Chang ◽  
Kuan-Fu Liao ◽  
Sheng-Chun Chiu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Kinase Inhibitor ◽  
Epithelial Mesenchymal Transition ◽  
Combined Treatment ◽  
Gelatin Zymography ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
Anti Cancer

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Regorafenib is a multi-kinase inhibitor and the second-line treatment for HCC. Since the PI3K/Akt/mTOR signaling pathway is dysregulated in HCC, we evaluated the therapeutic effects of regorafenib combined with a dual PI3K/mTOR inhibitor BEZ235 in the human HCC cell lines (n = 3). The combined treatment with BEZ235 and regorafenib enhanced the inhibition of cell proliferation and increased the expression of cleaved caspase-3 and cleaved PARP in HCC cells. Moreover, the combined treatment suppressed HCC cell migration and invasion in the transwell assay. Further, the Western blot analyses confirmed the involvement of epithelial-mesenchymal transition (EMT)-related genes such as slug, vimentin, and matrix metalloproteinase (MMP)-9/-2. Additionally, the proteinase activity of MMP-9/-2 was analyzed using gelatin zymography. Furthermore, the inhibition of phosphorylation of the Akt, mTOR, p70S6K, and 4EBP1 after combined treatment was validated using Western blot analysis. Therefore, these results suggest that the combined treatment with BEZ235 and regorafenib benefits patients with HCC.

Effect of tumor cell-derived debris and IgG on metastasis of pancreatic cancer and inflammation through tumor-associated macrophages.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15764-e15764
Author(s):  
Qi Zhang ◽  
Qi Chen ◽  
Xueli Bai ◽  
Jianxin Wang ◽  
Tingbo Liang
Keyword(s):  
Tumor Cell ◽  
Epithelial Mesenchymal Transition ◽  
Hepatoma Cell ◽  
Ductal Adenocarcinoma ◽  
M2 Macrophages ◽  
Tumor Associated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Mesenchymal Transition ◽  
Cox 2 ◽  
Anti Inflammatory

e15764 Background: The progression and metastasis of pancreatic ductal adenocarcinoma (PDAC) is highly dependent on the tumor microenvironment. Most tumor-associated macrophages (TAMs) are M2 phenotypic macrophages, which normally show anti-inflammatory functions in numerous disorders. We previously found that alternatively activated macrophages showed pro-inflammatory characteristics upon stimulation of hepatoma cell-derived debris, but the molecular mechanism was unclear. Methods: Macrophages were induced using tumor cell debris. Xenograft mouse model was established. Immunoblotting and immunochemistry were used to test protein expression. Results: The M2 macrophages-derived inflammation also existed in PDAC. We proved that the necrotic debris of PDAC cells induced potent IL-1β release by M2 macrophages via TLR4/TRIF/NF-κB signaling, and this effect was further boosted by IgG that also derived from PDAC cells. We further revealed that increased IL-1β promoted epithelial-mesenchymal transition (EMT) and consequent metastasis of PDAC cells. Using a selective COX-2 inhibitor celecoxib, we enhanced the anti-tumoral efficacy of gemcitabine. Conclusions: These data revealed a special pro-inflammatory phenomenon and mechanism in PDAC, and indicated that IL-1β and COX-2 can be therapeutic targets of anti-inflammatory strategy in PDAC treatment.

scholarly journals Exosome Release of Drugs: Coupling with Epithelial-Mesenchymal Transition

2019 ◽  
Author(s):  
Takanori Eguchi ◽  
Kisho Ono ◽  
Stuart Calderwood ◽  
Kuniaki Okamoto
Keyword(s):  
Drug Resistance ◽  
Stem Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cell Phenotype ◽  
Targeted Drugs ◽  
Mesenchymal Transition ◽  
Cancer Stem Cell Phenotype ◽  
Anti Cancer ◽  
Secretory Phenotype ◽  
Stem Cell Phenotype

Extracellular vesicles (EVs), such as exosomes or oncosomes are released with molecules unfavorable for survival from cells. In addition, accumulating evidence has shown that tumor cells often eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing, drug resistance phenotype is often coupled with cellular dedifferentiation and transformation, cells undergoing epithelial-mesenchymal transition (EMT) and taking on a cancer stem cell phenotype. Recent studies have shown that the release of EVs is also involved in immunosuppression. The concept of the resistance-associated secretory phenotype (RASP) is reviewed herein.

scholarly journals TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression

2021 ◽  
Vol 9 ◽  
Author(s):  
Chunfeng Xie ◽  
Jianyun Zhu ◽  
Xue Yang ◽  
Cong Huang ◽  
Liping Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tobacco Smoke ◽  
Epithelial Mesenchymal Transition ◽  
Suppressor Gene ◽  
Inhibitory Effect ◽  
Vimentin Expression ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients ◽  
Anti Cancer

As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.

scholarly journals 3,3′-Diindolylmethane Promotes Gastric Cancer Progression via β-TrCP-Mediated NF-κB Activation in Gastric Cancer-Derived MSCs

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Shi ◽  
Yaoxiang Sun ◽  
Hongru Ruan ◽  
Cheng Ji ◽  
Jiahui Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Multiple Drug Resistance ◽  
Cancer Drug ◽  
Multiple Drug ◽  
High Morbidity ◽  
Related Factors ◽  
Anti Cancer

Gastric cancer is a malignant tumor characterized by high morbidity and invasion. Surgery combined with chemo-radiotherapy is the most common treatment for gastric cancer, while multiple drug resistance always results in treatment failure. Once the anti-tumor drugs enter the tumor foci, tumor cells as well as those found in the microenvironment are affected. However, the effects of drugs on tumor microenvironment (TME) are easily overlooked. In this study, we investigated the effects of the anti-cancer drug 3,3’-diindolylmethane (DIM) on gastric cancer-derived mesenchymal stem cells (GC-MSCs) and their subsequent impact on cancer progression. Surprisingly, we found that the therapeutic concentration of DIM upregulated the expression level of tumor-related factors such as CCL-2, IL-6, and IL-8 in GC-MSCs. The conditioned medium of DIM-treated GC-MSCs promoted the proliferation, invasion, and migration of gastric cancer cells in vitro and tumor growth in vivo. Mechanistically, DIM enhanced the expression of β-TrCP, an E3 ubiquitin ligase leading to IκBα degradation and NF-κB activation in GC-MSCs. The β-TrCP knockdown partially eliminated positive results caused by DIM. Our results showed that the therapeutic dosage of DIM induced cell death in cancer cells, while enhancing MSC paracrine functions in the stroma to offset the original DIM effect on cancer cells. These findings provide a new mechanism of anti-cancer drug resistance and remind us to adjust the chemotherapeutic scheme by combining the anti-cancer drug with an appropriate signaling pathway inhibitor to block the side effects of drug on targeted TME cells.

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