The Great Escape: The Power of Cancer Stem Cells to Evade Programmed Cell Death

Castelli, Vanessa; Giordano, Antonio; Benedetti, Elisabetta; Giansanti, Francesco; Quintiliani, Massimiliano; Cimini, Annamaria

doi:10.3390/cancers13020328

Cited by 29 publications

(15 citation statements)

References 243 publications

(158 reference statements)

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“…In this aspect, the elusion of apoptosis is a remarkable phenomenon in cancers ( 28 ). Essentially, cancer cells display lessened apoptotic events that lead to assisting the progression and metastasis of cancer cells ( 29 , 30 ). Tumor cells evade the normal apoptosis and continue to multiply, obstructing the normal cells or tissue functions, which can lead to death.…”

Section: Discussionmentioning

confidence: 99%

Ononin Shows Anticancer Activity Against Laryngeal Cancer via the Inhibition of ERK/JNK/p38 Signaling Pathway

Ma²,

et al. 2022

Front. Oncol.

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BackgroundLaryngeal cancer is a type of head and neck tumor with a poor prognosis and survival rate. The new cases of laryngeal cancer increased rapidly with a higher mortality rate around the world.ObjectiveThe current research work was focused to unveil the in vitro antitumor effects of ononin against the laryngeal cancer Hep-2 cells.MethodologyThe cytotoxic effects of ononin against the laryngeal cancer Hep-2 cells and normal HuLa-PC laryngeal cells were studied using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The intracellular Reactive Oxygen Species (ROS) generation, apoptotic cell death, Mitochondrial Membrane Potential (MMP), and cell adhesion on the 25 and 50 µM ononin-treated Hep-2 cells were detected using respective staining assays. The levels of TBARS and antioxidants were assayed using specific kits. The expressions of c-Jun N-terminal kinase 1/2 (JNK1/2), Extracellular Signal-regulated Kinase 1/2 (ERK1/2), p38, Phosphatidylinositol-3 Kinase 1/2 (PI3K1/2), and protein kinase-B (Akt) in the ononin-treated Hep-2 cells were investigated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay.ResultsThe ononin treatment effectively inhibited the Hep-2 cell viability but did not affect the viability of HuLa-PC cells. Furthermore, the ononin treatment effectively improved the intracellular ROS accumulation, depleted the MMP, and triggered apoptosis in Hep-2 cells. The Thiobarbituric acid reactive substances (TBARS) were improved, and Glutathione (GSH) levels and Superoxide dismutase (SOD) were depleted in the ononin-administered Hep-2 cells. The ononin treatment substantially inhibited the JNK/ERK/p38 axis in the Hep-2 cells.ConclusionTogether, the outcomes of this exploration proved that the ononin has remarkable antitumor activity against laryngeal cancer Hep-2 cells.

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Section: Discussionmentioning

confidence: 99%

Ononin Shows Anticancer Activity Against Laryngeal Cancer via the Inhibition of ERK/JNK/p38 Signaling Pathway

Ma²,

et al. 2022

Front. Oncol.

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“…CSCs exhibit inherent resistance to apoptosis via a variety of mechanisms, including the overexpression of multidrug resistance transporters such as the ATP binding cassette (ABC) transporter family. ABC transporter overexpression has been documented in numerous malignancies, most noticeably in CSCs [ 138 ]. CSCs have been demonstrated to be enhanced in a variety of malignancies, leading to treatment resistance [ 139 ].…”

Section: Cancer Stem Cells In Evading Programmed Cell Deathmentioning

confidence: 99%

“…Autophagy is required for preservation of pluripotency or the ability to self-renew and remain undifferentiated which is an essential feature of CSCs [ 144 ]. In fact, it has been discovered that CSCs from various malignancies retain a strong autophagic flux [ 138 ], and along with hypoxia, it is required for the preservation of the stem cell niche. Interestingly, Zhu et al established that autophagy is HIF-1-dependent and essential for maintaining the balance between pancreatic CSCs and normal cancer cells [ 145 ].…”

Section: Cancer Stem Cells In Evading Programmed Cell Deathmentioning

confidence: 99%

Cancer Stem Cells: From an Insight into the Basics to Recent Advances and Therapeutic Targeting

Bisht

Nigam

Kunjwal

et al. 2022

Stem Cells International

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Cancer is characterized by an abnormal growth of the cells in an uncontrolled manner. These cells have the potential to invade and can eventually turn into malignancy, leading to highly fatal forms of tumor. Small subpopulations of cancer cells that are long-lived with the potential of excessive self-renewal and tumor formation are called cancer stem cells (CSCs) or cancer-initiating cells or tumor stem cells. CSCs can be found in tissues, such as breast, brain, lung, liver, ovary, and testis; however, their origin is still a matter of debate. These cells can differentiate and possess self-renewal capacity maintained by numerous intracellular signal transduction pathways, such as the Wnt/β-catenin signaling, Notch signaling, transforming growth factor-β signaling, and Hedgehog signaling. They can also contribute to numerous malignancies and are an important reason for tumor recurrence and metastasis because they are resistant to the known therapeutic strategies that mainly target the bulk of the tumor cells. This review contains collected and compiled information after analyzing published works of the last three decades. The goal was to gather information of recent breakthroughs related to CSCs, strategies to target CSCs’ niche (e.g., nanotechnology with tumor biology), and their signaling pathways for cancer therapy. Moreover, the role of metformin, an antidiabetic drug, acting as a chemotherapeutic agent on CSCs by inhibiting cellular transformation and its selective killing is also addressed.

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“…Besides, it shows apparent heterogeneity, [1] making the current personalized medical treatment of cancer reveal obvious limitations. In addition, there are many mechanisms to evade programmed cell death in cancer cells, [2] which poses challenges for effective cancer theranostics. The booming development of nanotechnology has provided new feedback, and cascade to generate structural changes to release detectable signals or molecules finally.…”

Section: Introductionmentioning

confidence: 99%

DNA Logic Circuits for Cancer Theranostics

Chen

Zhang

et al. 2022

Small

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solutions for precise cancer theranostics based on tumor microenvironment (TME) and biomarkers. [3][4][5][6][7] Nano-drugs such as liposomes, [8] polymer nanoparticles, [9] and inorganic nanoparticles [10] have been approved by Food and Drug Administration for the clinical treatment of cancer. However, current nanomedicine technologies lack intelligence which is the capability of autonomous computing in biological samples. Owing to the basepairing language and dynamic assembly of DNA strands, DNA-based logic devices/ circuits hold great potential to enhance the intelligence of nanomedicine.DNA nanotechnology began with the DNA four-arm junction structure proposed by Seeman in the 1980s. [11] On the basis of the Watson-Crick base pairing principle, such nanotechnology creates a variety of controllable nanoscale structures based on self-assembly of nucleic acid, and then built up static DNA nano structures such as DNA tiles and DNA origami by bottom-up approach. [12] The development of static DNA nanotechnology creates highly stable and variable DNA nanostructures showing the applications in nanomedicine including molecular imaging, drug delivery, biosensors, and the revolution of data storage. [13][14][15][16][17][18] Because nucleic acid materials have excellent structural controllability, biosafety, and functional diversity, they have emerged as excellent materials for the early diagnosis and timely treatment of cancer. [19] DNA nanotechnology had been further developed by Yurke et al. They constructed the first DNA molecular machine and proposed the concept of toehold-mediated strand displacement (TMSD) for the first time, [20] which opened a new era of dynamic DNA nanotechnology. Dynamic DNA nanotechnology utilizes a nonequilibrium nucleic acid system based on TMSD [21] or enzymatic reactions, to develop DNA nanomechanical devices, [22] and molecular logic networks. [23][24][25][26][27][28] Through the cascade and integration of multiple DNA reaction modules, DNA logic circuit is developed for cancer theranostics. [29,30] The basic DNA logic circuit can be conceptualized as a black box, which accepts the DNA strand as input and implements signal conversion by performing modular circuit elements such as TMSD and enzymatic reaction, [31] finally releases the DNA strand as output. [32] In cancer theranostics, DNA logic circuits can respond to the microenvironment or specific biomarkers of tumor, through signal transduction, logical judgment, signal amplification, Cancer diagnosis and therapeutics (theranostics) based on the tumor microenvironment (TME) and biomarkers has been an emerging approach for precision medicine. DNA nanotechnology dynamically controls the self-assembly of DNA molecules at the nanometer scale to construct intelligent DNA chemical reaction systems. The DNA logic circuit is a particularly emerging approach for computing within the DNA chemical systems. DNA logic circuits can sensitively respond to tumor-specific markers and the TME through logic operations and signal amplification, to genera...

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The Great Escape: The Power of Cancer Stem Cells to Evade Programmed Cell Death

Cited by 29 publications

References 243 publications

Ononin Shows Anticancer Activity Against Laryngeal Cancer via the Inhibition of ERK/JNK/p38 Signaling Pathway

Ononin Shows Anticancer Activity Against Laryngeal Cancer via the Inhibition of ERK/JNK/p38 Signaling Pathway

Cancer Stem Cells: From an Insight into the Basics to Recent Advances and Therapeutic Targeting

DNA Logic Circuits for Cancer Theranostics

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