The promising potential of piperlongumine as an emerging therapeutics for cancer

In spite of the immense advancement in the diagnostic and treatment modalities, cancer continues to be one of the leading causes of mortality across the globe, responsible for the death of around 10 million patients every year. The foremost challenges faced in the treatment of this disease are chemoresistance, adverse effects of the drugs, and the high cost of treatment. Though scientific studies over the past few decades have foreseen and are focusing on the cancer-preventive and therapeutic potential of natural products and their underlying mechanism of action, many more of these agents are not still explored. Piperlongumine (PL), or piplartine, is one such alkaloid isolated from Piper longum Linn. which is shown to be safe and has significant potential in the prevention and therapy of cancer. Numerous shreds of evidence have established the ability of this alkaloid and its analogs and nanoformulations in modulating various complex molecular pathways such as phosphatidylinositol-3-kinase/protein kinase B /mammalian target of rapamycin, nuclear factor kappa-B, Janus kinases/signal transducer and activator of transcription 3, etc. and inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases, etc. In addition, PL was also shown to inhibit radioresistance and chemoresistance and sensitize the cancer cells to the standard chemotherapeutic agents. Therefore, this compound has high potential as a drug candidate for the prevention and treatment of different cancers. The current review briefly reiterates the anti-cancer properties of PL against different types of cancer, which permits further investigation by conducting clinical studies.

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The Anti-fibrotic Effect of Human Fetal Skin-derived Stem Cell Secretome on the Liver Fibrosis

10.21203/rs.3.rs-39850/v1 ◽

2020 ◽

Author(s):

Xia Yao ◽

Jing Wang ◽

Jiajing Zhu ◽

Xiaoli Rong

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Fetal Skin ◽

Mesenchymal Transition ◽

Cell Based Therapy ◽

Causes Of Mortality ◽

Smad7 Expression

Abstract Background: Liver fibrosis resulting from chronic liver injury is one of the major causes of mortality worldwide. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease, while maintaining its advantages.Methods: In this study, we investigated the effect ofhuman fetal skin-derived stem cells (hFFSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFFSCssecretome in liver fibrosis, we established the CCl4-induced rat liver fibrosis model, and administered hFFSCssecretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFFSCssecretome in hepatic stellate cells (HSCs).Results: Our results showed that hFFSCssecretomeffectively reduced collagen content in liver, improved the liver function and promoted liver regeneration. Interestingly, we also found thathFFSCssecretom reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSCsecretom inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, however, increased Smad7 expression.Conclusions: In conclusions, our results suggest that hFFSCssecretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

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Human fetal skin-derived stem cell secretome reduce liver fibrosis

10.21203/rs.3.rs-19079/v2 ◽

2020 ◽

Author(s):

Xia Yao ◽

Jing Wang ◽

Jiajing Zhu ◽

Xiaoli Rong

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Fetal Skin ◽

Mesenchymal Transition ◽

Cell Based Therapy ◽

Current Therapies ◽

Causes Of Mortality

Abstract Background: Liver fibrosis resulting from a chronic liver injury is one of the significant causes of mortality. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease while maintaining its advantages over the current therapies. Methods: In this study, we investigated the effect of human fetal skin-derived stem cells (hFSSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFSSCs secretome in liver fibrosis, we established the CCl4-induced liver fibrosis rat model, and we administered hFSSCs secretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFSSCs secretome in hepatic stellate cells (HSCs). Results: Our results showed that hFSSCs secretome effectively reduced collagen content in the liver, and improved the liver function and promoted liver regeneration. Interestingly, we also found that hFSSCs secretome reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSC secretome inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, while we observed, increased Smad7 expression. Conclusions: In conclusion, our results suggest that hFSSCs secretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

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The Role of the Receptor Tyrosine Kinase Axl in Carcinogenesis and Development of Therapeutic Resistance: An Overview of Molecular Mechanisms and Future Applications

Cancers ◽

10.3390/cancers13071521 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1521

Author(s):

Martha Wium ◽

Aderonke F. Ajayi-Smith ◽

Juliano D. Paccez ◽

Luiz F. Zerbini

Keyword(s):

Drug Resistance ◽

Tyrosine Kinase ◽

Cancer Progression ◽

Receptor Tyrosine Kinase ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Chemotherapeutic Agents ◽

Mesenchymal Transition ◽

Development Of Resistance

Resistance to chemotherapeutic agents by cancer cells has remained a major obstacle in the successful treatment of various cancers. Numerous factors such as DNA damage repair, cell death inhibition, epithelial–mesenchymal transition, and evasion of apoptosis have all been implicated in the promotion of chemoresistance. The receptor tyrosine kinase Axl, a member of the TAM family (which includes TYRO3 and MER), plays an important role in the regulation of cellular processes such as proliferation, motility, survival, and immunologic response. The overexpression of Axl is reported in several solid and hematological malignancies, including non-small cell lung, prostate, breast, liver and gastric cancers, and acute myeloid leukaemia. The overexpression of Axl is associated with poor prognosis and the development of resistance to therapy. Reports show that Axl overexpression confers drug resistance in lung cancer and advances the emergence of tolerant cells. Axl is, therefore, an important candidate as a prognostic biomarker and target for anticancer therapies. In this review, we discuss the consequence of Axl upregulation in cancers, provide evidence for its role in cancer progression and the development of drug resistance. We will also discuss the therapeutic potential of Axl in the treatment of cancer.

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The Non-Coding RNAs Inducing Drug Resistance in Ovarian Cancer: A New Perspective for Understanding Drug Resistance

Frontiers in Oncology ◽

10.3389/fonc.2021.742149 ◽

2021 ◽

Vol 11 ◽

Author(s):

Gaofeng Li ◽

Jun Gong ◽

Shulong Cao ◽

Zhaoyang Wu ◽

Dong Cheng ◽

...

Keyword(s):

Ovarian Cancer ◽

Drug Resistance ◽

Epithelial Mesenchymal Transition ◽

Underlying Mechanism ◽

Chemotherapeutic Agents ◽

Circular Rnas ◽

Cancer Resistance ◽

Chemotherapeutic Resistance ◽

Mesenchymal Transition ◽

Non Coding Rnas

Ovarian cancer, a common malignant tumor, is one of the primary causes of cancer-related deaths in women. Systemic chemotherapy with platinum-based compounds or taxanes is the first-line treatment for ovarian cancer. However, resistance to these chemotherapeutic drugs worsens the prognosis. The underlying mechanism of chemotherapeutic resistance in ovarian cancer remains unclear. Non-coding RNAs, including long non-coding RNAs, microRNAs, and circular RNAs, have been implicated in the development of drug resistance. Abnormally expressed non-coding RNAs can promote ovarian cancer resistance by inducing apoptosis inhibition, protective autophagy, abnormal tumor cell proliferation, epithelial-mesenchymal transition, abnormal glycolysis, drug efflux, and cancer cell stemness. This review summarizes the role of non-coding RNAs in the development of chemotherapeutic resistance in ovarian cancer, including their mechanisms, targets, and potential signaling pathways. This will facilitate the development of novel chemotherapeutic agents that can target these non-coding RNAs and improve ovarian cancer treatment.

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The anti-fibrotic effect of human fetal skin-derived stem cell secretome on the liver fibrosis

10.21203/rs.3.rs-41934/v1 ◽

2020 ◽

Author(s):

Xia Yao ◽

Jing Wang ◽

Jiajing Zhu ◽

Xiaoli Rong

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Fetal Skin ◽

Mesenchymal Transition ◽

Cell Based Therapy ◽

Current Therapies ◽

Causes Of Mortality

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Anti-fibrotic effect of human fetal skin-derived stem cell secretomeon the liver fibrosis

10.21203/rs.3.rs-19079/v3 ◽

2020 ◽

Author(s):

Xia Yao ◽

Jing Wang ◽

Jiajing Zhu ◽

Xiaoli Rong

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Fetal Skin ◽

Mesenchymal Transition ◽

Cell Based Therapy ◽

Current Therapies ◽

Causes Of Mortality

Abstract Background: Liver fibrosis resulting from a chronic liver injury is one of the significant causes of mortality. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease while maintaining its advantages over the current therapies.Methods: In this study, we investigated the effect of human fetal skin-derived stem cells (hFSSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFSSCs secretome in liver fibrosis, we established the CCl4-induced liver fibrosis rat model, and we administered hFSSCs secretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFSSCs secretome in hepatic stellate cells (HSCs). Results: Our results showed that hFSSCs secretome effectively reduced collagen content in the liver, and improved the liver function and promoted liver regeneration. Interestingly, we also found that hFSSCs secretome reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSC secretome inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, while we observed, increased Smad7 expression. Conclusions: In conclusion, our results suggest that hFSSCs secretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

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The Emerging Role of Metformin in the Prevention and Treatment of Colorectal Cancer: A Game Changer for Management of Colorectal Cancer

Current Diabetes Reviews ◽

10.2174/1573399818666211105125129 ◽

2021 ◽

Vol 18 ◽

Author(s):

Moein Ala

Keyword(s):

Colorectal Cancer ◽

Intestinal Inflammation ◽

Epithelial Mesenchymal Transition ◽

Chemotherapeutic Agents ◽

Advanced Adenoma ◽

High Risk Population ◽

Mesenchymal Transition ◽

Cytotoxicity Activity ◽

Increased Risk ◽

Patients With Diabetes

: Metformin is an old, inexpensive and relatively safe anti-diabetic medication which can decrease the increased risk of several types of cancer in patients with diabetes. Recent meta-analyses revealed that metformin markedly decreased the incidence of colorectal adenoma, advanced adenoma and colorectal cancer (CRC) among patients with diabetes. Potential mechanisms by which metformin may decrease colorectal cancer risk include its effects on ameliorating intestinal inflammation and dysbiosis, suppressing major proliferative pathways, preventing DNA replication, accelerating tumor cells apoptosis, inhibiting intra-tumor angiogenesis and epithelial-mesenchymal transition (EMT), increasing tumor-infiltrating lymphocytes and CD68+ tumor-associated macrophages, and enhancing T cell cytotoxicity activity. It was uncovered that metformin can improve overall survival and CRC-specific survival among patients with diabetes and CRC. Interestingly, metformin decreased the incidence of colonic adenoma in patients with acromegaly and reduced the incidence of inflammatory bowel disease (IBD) among patients with diabetes, which can indirectly lower the risk of CRC. Results of phase II clinical trials revealed that metformin can enhance the anti-cancer effects of chemotherapeutic agents, such as 5-Fluorouracil (5-FU) and irinotecan on refractory CRC. Furthermore, metformin decreased the risk of new polyps and adenomas in patients without diabetes. Regarding the results of previous preclinical and clinical studies, it is rational to assess the effect of metformin in normoglycemic patients with CRC and expand its clinical application for treating CRC or preventing it in a high-risk population.

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The Impacts of Bone Marrow Mesenchymal Stem Cells (BMSCs)-Derived Periostin on Epithelial-Mesenchymal Transition (EMT) of Cervical Cancer Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2958 ◽

2022 ◽

Vol 12 (4) ◽

pp. 820-826

Author(s):

Chengyong Wu ◽

Weifeng Wei ◽

Jing Li ◽

Shenglin Peng

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Signal Transduction Pathway ◽

Underlying Mechanism ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Essential Components ◽

Cervical Cancer Cells ◽

E Cadherin

Epithelial-mesenchymal transition (EMT) is closely related to the migrating and invading behaviors of cells. Periostin is one of the essential components in the extracellular matrix and can induce EMT of cells and their sequential metastasis. But its underlying mechanism is unclear. The Hela and BMSC cell lines were assigned into Periostin-mimic group, Periostin-Inhibitor group and Periostin-NC group followed by analysis of cell migration and invasion, expression of E-Cadherin, Vimentin, β-Catenin, Snail, MMP-2, MMP-9, PTEN, and p-PTEN. Cells in Periostin-mimic group exhibited lowest migration, least number of invaded cells, as well as lowest levels of Vimentin, β-Catenin, Snail, MMP-2, MMP-9, p-PTEN, Akt, p-Akt, p-GSK-3β, p-PDK1 and p-cRcf, along with highest levels of E-cadherin and PTEN. Moreover, cells in Periostin-NC group had intermediate levels of these above indicators, while, the Periostin-Inhibitor group exhibited the highest migration rate, the most number of invaded cells, and the highest levels of these proteins (P < 0.05). In conclusion, BMSCs-derived Periostin can influence the EMT of cervical cancer cells possibly through restraining the activity of the PI3K/AKT signal transduction pathway, indicating that Periostin might be a target of chemotherapy in clinics for the treatment of cervical cancer.

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Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition

Cellular Physiology and Biochemistry ◽

10.1159/000486123 ◽

2017 ◽

Vol 44 (6) ◽

pp. 2357-2367 ◽

Cited By ~ 3

Author(s):

Yiquan Wang ◽

Chencheng Dai ◽

Cheng Zhou ◽

Wenqu Li ◽

Yujia Qian ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Expression Patterns ◽

Underlying Mechanism ◽

Carcinoma Cells ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Female Reproductive Health ◽

Gene Microarray Analysis ◽

And Migration

Background/Aims: Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. Methods: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. Results: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. Conclusion: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.

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Protein kinase C inhibitors override ZEB1-induced chemoresistance in HCC

Cell Death and Disease ◽

10.1038/s41419-019-1885-6 ◽

2019 ◽

Vol 10 (10) ◽

Cited By ~ 3

Author(s):

Rahul Sreekumar ◽

Muhammad Emaduddin ◽

Hajir Al-Saihati ◽

Karwan Moutasim ◽

James Chan ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Epithelial Mesenchymal Transition ◽

Chemotherapeutic Agents ◽

Tumour Cells ◽

Mesenchymal Transition ◽

Kinase C ◽

Pkc Inhibitors ◽

Hcc Cells

Abstract Epithelial–mesenchymal transition (EMT) is a process by which tumour cells lose epithelial characteristics, become mesenchymal and highly motile. EMT pathways also induce stem cell features and resistance to apoptosis. Identifying and targeting this pool of tumour cells is a major challenge. Protein kinase C (PKC) inhibition has been shown to eliminate breast cancer stem cells but has never been assessed in hepatocellular cancer (HCC). We investigated ZEB family of EMT inducer expression as a biomarker for metastatic HCC and evaluated the efficacy of PKC inhibitors for HCC treatment. We showed that ZEB1 positivity predicted patient survival in multiple cohorts and also validated as an independent biomarker of HCC metastasis. ZEB1-expressing HCC cell lines became resistant to conventional chemotherapeutic agents and were enriched in CD44high/CD24low cell population. ZEB1- or TGFβ-induced EMT increased PKCα abundance. Probing public databases ascertained a positive association of ZEB1 and PKCα expression in human HCC tumours. Inhibition of PKCα activity by small molecule inhibitors or by PKCA knockdown reduced viability of mesenchymal HCC cells in vitro and in vivo. Our results suggest that ZEB1 expression predicts survival and metastatic potential of HCC. Chemoresistant/mesenchymal HCC cells become addicted to PKC pathway and display sensitivity to PKC inhibitors such as UCN-01. Stratifying patients according to ZEB1 and combining UCN-01 with conventional chemotherapy may be an advantageous chemotherapeutic strategy.

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