Bypassing Mechanisms of Mitochondria-Mediated Cancer Stem Cells Resistance to Chemo- and Radiotherapy

Cancer stem cells (CSCs) are highly resistant to conventional chemo- and radiotherapeutic regimes. Therefore, the multiple drug resistance (MDR) of cancer is most likely due to the resistance of CSCs. Such resistance can be attributed to some bypassing pathways including detoxification mechanisms of reactive oxygen and nitrogen species (RO/NS) formation or enhanced autophagy. Unlike in normal cells, where RO/NS concentration is maintained at certain threshold required for signal transduction or immune response mechanisms, CSCs may develop alternative pathways to diminish RO/NS levels leading to cancer survival. In this minireview, we will focus on elaborated mechanisms developed by CSCs to attenuate high RO/NS levels. Gaining a better insight into the mechanisms of stem cell resistance to chemo- or radiotherapy may lead to new therapeutic targets thus serving for better anticancer strategies.

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MDA-9/Syntenin (SDCBP) Is a Critical Regulator of Chemoresistance, Survival and Stemness in Prostate Cancer Stem Cells

Cancers ◽

10.3390/cancers12010053 ◽

2019 ◽

Vol 12 (1) ◽

pp. 53 ◽

Cited By ~ 7

Author(s):

Sarmistha Talukdar ◽

Swadesh K. Das ◽

Anjan K. Pradhan ◽

Luni Emdad ◽

Jolene J. Windle ◽

...

Keyword(s):

Prostate Cancer ◽

Stem Cells ◽

Drug Resistance ◽

Stem Cell ◽

Cancer Stem Cells ◽

Multiple Drug Resistance ◽

Trichostatin A ◽

Tumor Formation ◽

Multiple Drug ◽

Prostate Cancer Stem Cells

Despite some progress, treating advanced prostate cancer remains a major clinical challenge. Recent studies have shown that prostate cancer can originate from undifferentiated, rare, stem cell-like populations within the heterogeneous tumor mass, which play seminal roles in tumor formation, maintenance of tumor homeostasis and initiation of metastases. These cells possess enhanced propensity toward chemoresistance and may serve as a prognostic factor for prostate cancer recurrence. Despite extensive studies, selective targeted therapies against these stem cell-like populations are limited and more detailed experiments are required to develop novel targeted therapeutics. We now show that MDA-9/Syntenin/SDCBP (MDA-9) is a critical regulator of survival, stemness and chemoresistance in prostate cancer stem cells (PCSCs). MDA-9 regulates the expression of multiple stem-regulatory genes and loss of MDA-9 causes a complete collapse of the stem-regulatory network in PCSCs. Loss of MDA-9 also sensitizes PCSCs to multiple chemotherapeutics with different modes of action, such as docetaxel and trichostatin-A, suggesting that MDA-9 may regulate multiple drug resistance. Mechanistically, MDA-9-mediated multiple drug resistance, stemness and survival are regulated in PCSCs through activation of STAT3. Activated STAT3 regulates chemoresistance in PCSCs through protective autophagy as well as regulation of MDR1 on the surface of the PCSCs. We now demonstrate that MDA-9 is a critical regulator of PCSC survival and stemness via exploiting the inter-connected STAT3 and c-myc pathways.

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Abstract 4373: Targeting lung cancer stem cells with inhibition of multiple drug resistance by demethoxylcurcumin-carrying chitosan-antibody core-shell nanoparticles

10.1158/1538-7445.am2015-4373 ◽

2015 ◽

Author(s):

Shih-Hwa Chiou

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Drug Resistance ◽

Cancer Stem Cells ◽

Multiple Drug Resistance ◽

Multiple Drug ◽

Core Shell ◽

Shell Nanoparticles ◽

Lung Cancer Stem Cells ◽

Core Shell Nanoparticles

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Properties and identification of cancer stem cells: A changing insight into intractable cancer

Surgery Today ◽

10.1007/s00595-009-4106-6 ◽

2010 ◽

Vol 40 (7) ◽

pp. 608-613 ◽

Cited By ~ 4

Author(s):

Norikatsu Miyoshi ◽

Hideshi Ishii ◽

Mitsugu Sekimoto ◽

Naotsugu Haraguchi ◽

Yuichiro Doki ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Insight Into

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Bioinformatics Studies Provide Insight into Possible Target and Mechanisms of Action of Nobiletin against Cancer Stem Cells

Asian Pacific Journal of Cancer Prevention ◽

10.31557/apjcp.2020.21.3.611 ◽

2020 ◽

Vol 21 (3) ◽

pp. 611-620 ◽

Cited By ~ 1

Author(s):

Adam Hermawan ◽

Herwandhani Putri

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Mechanisms Of Action ◽

Insight Into

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Are Leukaemic Stem Cells Restricted to a Single Cell Lineage?

International Journal of Molecular Sciences ◽

10.3390/ijms21010045 ◽

2019 ◽

Vol 21 (1) ◽

pp. 45 ◽

Cited By ~ 1

Author(s):

Geoffrey Brown ◽

Lucía Sánchez ◽

Isidro Sánchez-García

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Lymphoblastic Leukaemia ◽

Cell Lineage ◽

Cell Development ◽

Haematopoietic Stem Cell ◽

Essential Difference ◽

Normal Cells

Cancer-stem-cell theory states that most, if not all, cancers arise from a stem/uncommitted cell. This theory revolutionised our view to reflect that cancer consists of a hierarchy of cells that mimic normal cell development. Elegant studies of twins who both developed acute lymphoblastic leukaemia in childhood revealed that at least two genomic insults are required for cancer to develop. These ‘hits’ do not appear to confer a growth advantage to cancer cells, nor do cancer cells appear to be better equipped to survive than normal cells. Cancer cells created by investigators by introducing specific genomic insults generally belong to one cell lineage. For example, transgenic mice in which the LIM-only 2 (LMO2, associated with human acute T-lymphoblastic leukaemia) and BCR-ABLp210 (associated with human chronic myeloid leukaemia) oncogenes were active solely within the haematopoietic stem-cell compartment developed T-lymphocyte and neutrophil lineage-restricted leukaemia, respectively. This recapitulated the human form of these diseases. This ‘hardwiring’ of lineage affiliation, either throughout leukaemic stem cell development or at a particular stage, is different to the behaviour of normal haematopoietic stem cells. While normal cells directly commit to a developmental pathway, they also remain versatile and can develop into a terminally differentiated cell that is not part of the initial lineage. Many cancer stem cells do not have this versatility, and this is an essential difference between normal and cancer stem cells. In this report, we review findings that support this notion.

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Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy

Pharmaceutics ◽

10.3390/pharmaceutics13081120 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1120

Author(s):

Lucia Ruxandra Tefas ◽

Cristina Barbălată ◽

Cristian Tefas ◽

Ioan Tomuță

Keyword(s):

Drug Delivery ◽

Stem Cells ◽

Cancer Therapy ◽

Cancer Stem Cells ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Collateral Damage ◽

Selective Cytotoxicity ◽

Initiation And Propagation ◽

Insight Into

Cancer stem cells (CSCs) are reportedly responsible for the initiation and propagation of cancer. Since CSCs are highly resistant to conventional chemo- and radiotherapy, they are considered the main cause of cancer relapse and metastasis. Salinomycin (Sali), an anticoccidial polyether antibiotic, has emerged as a promising new candidate for cancer therapy, with selective cytotoxicity against CSCs in various malignancies. Nanotechnology provides an efficient means of delivering Sali to tumors in view of reducing collateral damage to healthy tissues and enhancing the therapeutic outcome. This review offers an insight into the most recent advances in cancer therapy using Sali-based nanocarriers.

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