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

: 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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The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽

10.3390/cancers13081833 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1833

Author(s):

Tsai-Tsen Liao ◽

Wei-Chung Cheng ◽

Chih-Yung Yang ◽

Yin-Quan Chen ◽

Shu-Han Su ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Cell Motility ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Cell Stiffness ◽

Mesenchymal Transition ◽

Cytoskeletal Dynamics ◽

Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

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Simulation of Radiotherapy Effects on Destroying Cancer Cells and Cancer Stem Cells

2020 27th National and 5th International Iranian Conference on Biomedical Engineering (ICBME) ◽

10.1109/icbme51989.2020.9319445 ◽

2020 ◽

Author(s):

Golara Aghebati ◽

Nadia Naghavi ◽

Behnaz Gheflati ◽

Shokouhozaman Soleymanifard

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Cells

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Hampering Stromal Cells in the Tumor Microenvironment as a Therapeutic Strategy to Destem Cancer Stem Cells

Cancers ◽

10.3390/cancers13133191 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3191

Author(s):

Katherine Po Sin Chung ◽

Rainbow Wing Hei Leung ◽

Terence Kin Wah Lee

Keyword(s):

Stem Cells ◽

Tumor Microenvironment ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Stromal Cells ◽

Current Knowledge ◽

Special Focus ◽

Intrinsic Regulation ◽

Mechanistic Basis ◽

Novel Therapeutic Strategies

Cancer stem cells (CSCs) within the tumor bulk play crucial roles in tumor initiation, recurrence and therapeutic resistance. In addition to intrinsic regulation, a growing body of evidence suggests that the phenotypes of CSCs are also regulated extrinsically by stromal cells in the tumor microenvironment (TME). Here, we discuss the current knowledge of the interplay between stromal cells and cancer cells with a special focus on how stromal cells drive the stemness of cancer cells and immune evasive mechanisms of CSCs. Knowledge gained from the interaction between CSCs and stromal cells will provide a mechanistic basis for the development of novel therapeutic strategies for the treatment of cancers.

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Codelivery of salinomycin and doxorubicin using nanoliposomes for targeting both liver cancer cells and cancer stem cells

Nanomedicine ◽

10.2217/nnm-2016-0137 ◽

2016 ◽

Vol 11 (19) ◽

pp. 2565-2579 ◽

Cited By ~ 27

Author(s):

Zhirong Gong ◽

Dazhong Chen ◽

Fangyuan Xie ◽

Junjie Liu ◽

He Zhang ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Liver Cancer ◽

Cancer Cells ◽

Liver Cancer Cells

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HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property in an NFκB-dependent way

Bioscience Reports ◽

10.1042/bsr20180829 ◽

2019 ◽

Vol 39 (3) ◽

Cited By ~ 1

Author(s):

Wenxiang Wang ◽

Yuxia Gao ◽

Jing Hai ◽

Jing Yang ◽

Shufeng Duan

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Drug Sensitivity ◽

Ovarian Cancer Cells ◽

Her2 Overexpression ◽

Her2 Positive ◽

Ovarian Cancer Stem Cells

Abstract Increasing evidence shows that cancer stem cells are responsible for drug resistance and relapse of tumors. In breast cancer, human epidermal growth factor receptor 2 (HER2) induces Herceptin resistance by inducing cancer stem cells. In the present study, we explored the effect of HER2 on cancer stem cells induction and drug sensitivity of ovarian cancer cell lines. First, we found that HER2 overexpression (HER2 OE) induced, while HER2 knockdown (HER2 KD) decreased CD44+/CD24− population. Consistently, HER2 expression was closely correlated with the sphere formation efficiency (SFE) of ovarian cancer cells. Second, we found that NFκB inhibition by specific inhibitor JSH23 or siRNA targetting subunit p65 dramatically impaired the induction of ovarian cancer stem cells by HER2, indicating that NFκB mediated HER2-induced ovarian cancer stem cells. Third, we found that HER2 KD significantly attenuated the tumorigenicity of ovarian cancer cells. Further, we found that HER2 inhibition increased drastically the sensitivity of ovarian cancer cells to doxorubicin (DOX) or paclitaxel (PTX). Finally, we examined the correlation between HER2 status and stem cell-related genes expression in human ovarian tumor tissues, and found that expressions of OCT4, COX2, and Nanog were higher in HER2 positive tumors than in HER2 negative tumors. Consistently, the 5-year tumor-free survival rate of HER2 positive patients was dramatically lower than HER2 negative patients. Taken together, our data indicate that HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property.

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