scholarly journals Mechanism of Overcoming Oxaliplatin Resistance Using HT29 Subcloning

2020 ◽  
Author(s):  
Jisu Lee ◽  
MI YOON KIM ◽  
Woomi Yang ◽  
Il-woung Kim ◽  
Seung-Kiel Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cell Line ◽  
Chemotherapy Resistance ◽  
Cancer Drug ◽  
Cancer Tissue ◽  
Chemotherapeutic Drugs ◽  
Slow Growing ◽  
Personalized Chemotherapy

Abstract Background: Cancer cells are different from normal healthy cells even though they reside within the same tissue and adapt to others. This intra-tumoral heterogeneity is the reason for chemo-resistance, and the emergence of one or more clones, which are resistant to chemotherapeutic drugs, causing clonal outgrowth to form recurrent cancer mass. The need for personalized chemotherapy is increasing because of the tumor heterogeneity and diverse mechanism of chemotherapy resistance. The recent accumulation of extensive evidence for the existence of cancer stem cells strengthens the cancer stem cell hypothesis for chemotherapy resistance and relapse. The development of a primary culture of cancer cells is essential for functional analysis like the sensitivity of chemotherapeutic drugs and the evaluation of the characteristics of cancer stem cells. Methods: We used a clonal cylinder to establish sub-clones originated from a single cell. Twenty-two sub-clones were successfully established, and eleven clones were selected according to their growth rate and analyzed. The sub-clones with low expression of BRAF, MEK2, and ERK, but not EGFR or KRAS, showed a correlation with the doubling time. We grouped the sub-clones as the fast-growing group and the slow-growing group of the HT29 cell line. Three out of five slow-growing sub-clones showed resistance to oxaliplatin treatment. All oxaliplatin-resistant sub-clones overexpressed ABCC2, and no relevance was found with ABCB1 and ABCG2. Active efflux of the drug by ABCC2, but not by ABCB1 or ABCG2, was confirmed with the inhibitor study using each specific inhibitor. The viability of resistant sub-clones decreased after the MK571 treatment, but other clones were not responsive. CD44 expression in oxaliplatin-resistant sub-clones was higher than that of sensitive clones. Conclusions: This study provides definite evidence of heterogeneity using a cancer cell line. Based on our studies, it appears that intra-tumoral heterogeneity of human cancer tissue is responsible for the development of chemotherapy resistance in cancer. These sub-clones are an excellent model for testing efficacy of anti-cancer drug candidates for advanced cancer therapy. The experimental design and concept of this study could be applied to personalized chemotherapy.

scholarly journals TAB2 Promotes the Stemness and Biological Functions of Cervical Squamous Cell Carcinoma Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yijia Zhou ◽  
Yuandong Liao ◽  
Chunyu Zhang ◽  
Junxiu Liu ◽  
Wei Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cell Function ◽  
Chemotherapy Resistance ◽  
Cervical Squamous Cell Carcinoma ◽  
Published Data ◽  
Cell Functions

Cancer stem cells are a key population participating in the promotion of the cervical cancer progression through interacting with cancer cells. Existing studies have preliminary revealed that cervical cancer stem cells contribute to tumor recurrence and chemotherapy resistance. However, the specific mechanisms involved in regulating cell functions remain largely unknown. Here, we analyzed published data from public databases and our global transcriptome data, thus identifying cancer-related signaling pathways and molecules. According to our findings, upregulated TAB2 was correlated to stem cell-like properties of cervical cancer. Immunohistochemistry staining of TAB2 in normal and cervical cancer tissues was performed. The cell function experiments demonstrated that knockdown of TAB2 reduced the stemness of cervical cancer cells and, importantly, prevented cervical cancer progression. Collectively, the therapeutic scheme targeting TAB2 may provide an option for overcoming tumor relapse and chemoresistance of cervical cancer via obstructing stemness maintenance.

Ovarian cancer stem cells (OCSCs): Therapy for advanced chemoresistant ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16542-e16542
Author(s):  
Prattusha Sengupta ◽  
Sudeshna Gangopadhyay ◽  
Saubhik Sengupta ◽  
Ujjal Kanti Ray ◽  
Ashis Mukhopadhyay
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Drug Sensitivity ◽  
Ex Vivo ◽  
Cancer Site ◽  
Chemotherapeutic Drugs ◽  
Ovarian Cancer Stem Cells

e16542 Background: Invasive and mesenchymal property of Ovarian Cancer Stem Cells (OCSCs)with CD44+/CD133+has made them promising target for targeted treatment. Chemotherapy treatment uses medicine to weaken and destroy cancer cells in body, including cells at original cancer site and any cancer cells that may have spread to another part of body. Chemotherapeutic drugs for advanced chemo-resistant ovarian cancer are yet to be well defined. Combination of drugs is also not fully known. Our objective is to define chemotherapeutic drugs and its action in OCSC which is the major reason for chemo resistance in case of advanced chemo-resistant ovarian cancer patients. Methods: A total of twenty biopsy proven advanced chemo-resistant ovarian cancer patients in the age group of 22-36 years were selected randomly and tested for CD44/CD133 via flow cytometry. Isolated OCSCs were cultured for ex vivo drug sensitivity towards platinum, anthracyclin, docetaxel, rapamycin, sunitinib, sorafenib and gefitinib. Correlation was drawn between cell differentiations, % of stem cells and drug response. Accordingly chemotherapy was designed for a particular patient. Results: We detected OCSCs in 90% of cases. Among positive samples ex vivo drug sensitivity was seen in 4(20%) to rapamycin, 1(5%) to sunitinib, 1(5%) to sorafenib, 1(5%) to gefitinib, 3(15%) to platinum, 1(5%) to anthracyclin, 1(5%) to docetaxel and rest showed no sensitivity to any drug. Conclusions: Thus primary aim to target OCSCs at onset of tumors in ovarian cancer patients to control metastasis and relapse of disease was somewhat obtained. Most interestingly, we found that the chemotherapeutic drugs which were less prescribed for ovarian cancer showed greater sensitivity in comparison to the widely used ones. We like to do animal model study followed by phase I, II and III human clinical trial to establish our hypothesis for better management of chemo-resistant ovarian cancer.

scholarly journals PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Pramod Darvin ◽  
Varun Sasidharan Nair ◽  
Eyad Elkord
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cell Line ◽  
Histone Modifications ◽  
Immune Evasion ◽  
Breast Cancer Cells ◽  
Posttranslational Histone Modifications ◽  
Mcf 7

Tumor progression through immune evasion is a major challenge in cancer therapy. Recent studies revealed that enhanced PD-L1 expression in cancer stem cells is linked to immune evasion. Understanding the mechanisms behind this PD-L1 overexpression in cancer stem cells is critical for developing more effective strategies for preventing immune evasion and increasing the efficacy of anti-PD-1/PD-L1 therapy. Tumorsphere formation in breast cancer cells enhanced epithelial to mesenchymal transition (EMT), which is evident by increased expression of mesenchymal markers. In this study, we analyzed CpG methylation of PD-L1 promoter in MCF-7 and BT-549 breast cancer cells and tumorspheres derived from them. PD-L1 promoter was significantly hypomethylated in MCF-7 tumorspheres, but not from BT-549 tumorspheres, compared with their cell line counterparts. The active demethylation of PD-L1 promoter was confirmed by the increase in the distribution of 5hmC and decrease in 5mC levels and the upregulation of TET3 and downregulation of DNMTs enzymes in MCF-7 tumorspheres, compared with the cell line. Additionally, we checked the distribution of repressive histones H3K9me3, H3K27me3, and active histone H3K4me3 in the PD-L1 promoter. We found that distribution of repressive histones to the PD-L1 promoter was lower in tumorspheres, compared with cell lines. Moreover, an overexpression of histone acetylation enzymes was observed in tumorspheres suggesting the active involvement of histone modifications in EMT-induced PD-L1 expression. In summary, EMT-associated overexpression of PD-L1 was partially independent of promoter CpG methylation and more likely to be dependent on posttranslational histone modifications.

miRNAs expressed differently in cancer stem cells and cancer cells of human gastric cancer cell line MKN-45

2012 ◽  
Vol 30 (5) ◽  
pp. 411-418 ◽  
Author(s):  
Azadeh Fahim Golestaneh ◽  
Amir Atashi ◽  
Lida Langroudi ◽  
Abbas Shafiee ◽  
Nasser Ghaemi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Human Gastric Cancer

scholarly journals A triple-drug nanotherapy to target breast cancer cells, cancer stem cells, and tumor vasculature

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara El-Sahli ◽  
Khang Hua ◽  
Andrew Sulaiman ◽  
Jason Chambers ◽  
Li Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Ex Vivo ◽  
Chemotherapeutic Agents ◽  
Hybrid Nanoparticles ◽  
Cancer Drug ◽  
Vascular Disrupting Agent

AbstractTriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, accounting for the majority of breast cancer-related death. Due to the lack of specific therapeutic targets, chemotherapeutic agents (e.g., paclitaxel) remain the mainstay of systemic treatment, but enrich a subpopulation of cells with tumor-initiating capacity and stem-like characteristics called cancer stem cells (CSCs); thus development of a new and effective strategy for TNBC treatment is an unmet medical need. Cancer nanomedicine has transformed the landscape of cancer drug development, allowing for a high therapeutic index. In this study, we developed a new therapy by co-encapsulating clinically approved drugs, such as paclitaxel, verteporfin, and combretastatin (CA4) in polymer-lipid hybrid nanoparticles (NPs) made of FDA-approved biomaterials. Verteporfin is a drug used in the treatment of macular degeneration and has recently been found to inhibit the Hippo/YAP (Yes-associated protein) pathway, which is known to promote the progression of breast cancer and the development of CSCs. CA4 is a vascular disrupting agent and has been tested in phase II/III of clinical trials. We found that our new three drug-NP not only effectively inhibited TNBC cell viability and cell migration, but also significantly diminished paclitaxel-induced and/or CA4-induced CSC enrichment in TNBC cells, partially through inhibiting the upregulated Hippo/YAP signaling. Combination of verteporfin and CA4 was also more effective in suppressing angiogenesis in an in vivo zebrafish model than single drug alone. The efficacy and application potential of our triple drug-NPs were further assessed by using clinically relevant patient-derived xenograft (PDX) models. Triple drug-NP effectively inhibited the viability of PDX organotypic slide cultures ex vivo and stopped the growth of PDX tumors in vivo. This study developed an approach capable of simultaneously inhibiting bulk cancer cells, CSCs, and angiogenesis.

scholarly journals Ovarian Cancer Stemness: Biological and Clinical Implications for Metastasis and Chemotherapy Resistance

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 907 ◽  
Author(s):  
Takeshi Motohara ◽  
Hidetaka Katabuchi
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Chemotherapy Resistance ◽  
Clinical Implications ◽  
Ovarian Cancer Stem Cells

Epithelial ovarian cancer is a highly lethal gynecological malignancy that is characterized by the early development of disseminated metastasis. Though ovarian cancer has been generally considered to preferentially metastasize via direct transcoelomic dissemination instead of the hematogenous route, emerging evidence has indicated that the hematogenous spread of cancer cells plays a larger role in ovarian cancer metastasis than previously thought. Considering the distinctive biology of ovarian cancer, an in-depth understanding of the biological and molecular mechanisms that drive metastasis is critical for developing effective therapeutic strategies against this fatal disease. The recent “cancer stem cell theory” postulates that cancer stem cells are principally responsible for tumor initiation, metastasis, and chemotherapy resistance. Even though the hallmarks of ovarian cancer stem cells have not yet been completely elucidated, metastasized ovarian cancer cells, which have a high degree of chemoresistance, seem to manifest cancer stem cell properties and play a key role during relapse at metastatic sites. Herein, we review our current understanding of the cell-biological mechanisms that regulate ovarian cancer metastasis and chemotherapy resistance, with a pivotal focus on ovarian cancer stem cells, and discuss the potential clinical implications of evolving cancer stem cell research and resultant novel therapeutic approaches.

Targeting Cancer Stem Cells and Non-Stem Cancer Cells: The Potential of Lipid- Based Nanoparticles

2018 ◽  
Vol 23 (43) ◽  
pp. 6563-6572
Author(s):  
Ana Filipa Cruz ◽  
Nuno Andre Fonseca ◽  
Vera Moura ◽  
Sergio Simoes ◽  
Joao Nuno Moreira
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells

Comparison of the Growth Curves of Cancer Cells and Cancer Stem Cells

2014 ◽  
Vol 9 (2) ◽  
pp. 112-116 ◽  
Author(s):  
Maria Toloudi ◽  
Eleni Ioannou ◽  
Marina Chatziioannou ◽  
Panagiotis Apostolou ◽  
Christos Kiritsis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Growth Curves

Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Shahram Taeb ◽  
Hamed Haghi-Aminjan ◽  
Shima Afrashi ◽  
Kave Moloudi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Fas Ligand ◽  
Inhibitory Effect ◽  
Mitochondrial Pathway ◽  
Multi Drug Resistance ◽  
Chemotherapy Drugs ◽  
Normal Tissues ◽  
Anti Cancer

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.

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