Stem cells in cancer therapy: opportunities and challenges

Zhang, Cheng Liang; Huang, Ting; Wu, Bi Li; He, Wen Xi; Liu, Dong

doi:10.18632/oncotarget.20798

Cited by 153 publications

(82 citation statements)

References 81 publications

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“…In spite of their potential therapeutic applications, their use is associated with some concerns including sharing the characteristic of self-renewal and plasticity with cancer cells that may lead to tumor development [ 29 ]. Challenges such as durability of treatment and tumorigenesis mandate further studies to improve their therapeutic efficacy and applicability in clinical practice [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

The role of mesenchymal stem cells in chemotherapy-induced gonadotoxicity

et al. 2018

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BackgroundThe therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) against cisplatin-induced nephrotoxicity has been reported, however, its efficacy in gonadotoxicity still has not been addressed. Herein, we investigated the effect of BM-MSCs in cisplatin-induced testicular toxicity and its underlying mechanism of action.MethodsThirty male Sprague–Dawley rats were divided into a control group: injected with phosphate-buffered saline (PBS) intraperitoneal (ip), a cisplatin group: injected with a single dose of 7 mg/kg cisplatin ip to induce gonadotoxicity and a BM-MSCs group: received cisplatin ip followed by BM-MSCs injection 1 day after cisplatin. In testicular tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) levels were assessed. Additionally, gene expressions of inducible nitric oxide synthase (iNOS), caspase-3, and p38 mitogen-activated protein kinase (MAPK) were measured. The testicular tumor necrosis factor alpha (TNF-α) protein contents and Bcl-2 associated X protein (BAX) expression were determined. Histopathology of testicular tissues was examined.ResultsCisplatin injection showed a significant decrease in GSH and SOD testicular levels besides a significant increase of MDA and TNF-α testicular levels and upregulation of testicular gene expressions of iNOS, caspase-3, and p38-MAPK in comparison to the control group. Moreover, a marked increase in BAX protein expression was observed in the cisplatin group when compared with the control one. Histopathological examination exhibited significant seminiferous tubules atrophy in cisplatin-treated rats.ConclusionsThe BM-MSCs injection significantly repaired the testicular injury and improved both biochemical and histopathological changes. The MSCs mitigated the gonadotoxicity induced by cisplatin through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

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Section: Discussionmentioning

confidence: 99%

The role of mesenchymal stem cells in chemotherapy-induced gonadotoxicity

et al. 2018

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“…At the same time, a small population of cells within a tumor, known as cancer stem cells (CSCs), are resistant to traditional cancer treatment (Weiswald et al ., ; Zhang et al ., ). The CSCs hypothesis postulates that a subpopulation of malignant cells constantly supplies the tumor with cancerous cells.…”

Section: Introductionmentioning

confidence: 97%

Selective induction of cancer cell death by VDAC1‐based peptides and their potential use in cancer therapy

et al. 2018

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Mitochondrial VDAC1 mediates cross talk between the mitochondria and other parts of the cell by transporting anions, cations, ATP, Ca2+, and metabolites and serves as a key player in apoptosis. As such, VDAC1 is involved in two important hallmarks of cancer development, namely energy and metabolic reprograming and apoptotic cell death evasion. We previously developed cell‐penetrating VDAC1‐derived peptides that interact with hexokinase (HK), Bcl‐2, and Bcl‐xL to prevent the anti‐apoptotic activities of these proteins and induce cancer cell death, with a focus on leukemia and glioblastoma. In this study, we demonstrated the sensitivity of a panel of genetically characterized cancer cell lines, differing in origin and carried mutations, to VDAC1‐based peptide‐induced apoptosis. Noncancerous cell lines were less affected by the peptides. Furthermore, we constructed additional VDAC1‐based peptides with the aim of improving targeting, selectivity, and cellular stability, including R‐Tf‐D‐LP4, containing the transferrin receptor internalization sequence (Tf) that allows targeting of the peptide to cancer cells, known to overexpress the transferrin receptor. The mode of action of the VDAC1‐based peptides involves HK detachment, interfering with the action of anti‐apoptotic proteins, and thus activating multiple routes leading to an impairment of cell energy and metabolism homeostasis and the induction of apoptosis. Finally, in xenograft glioblastoma, lung, and breast cancer mouse models, R‐Tf‐D‐LP4 inhibited tumor growth while inducing massive cancer cell death, including of cancer stem cells. Thus, VDAC1‐based peptides offer an innovative new conceptual framework for cancer therapy.

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“…According to the cancer stem cell (CSC) theory, a small subpopulation of cells share embryonic stem cell characteristics, 2 giving rise to metastatic cancer cells and responsible for the high rate of recurrence. 37 Indeed, CSCs share the same major signaling pathways with embryonic stem cells, including the Wnt, Notch, transforming growth factor beta (TGF-b), and Hedgehog signaling pathways. 38 Nevertheless, quiescent CSCs express stemness genes, have the capability to self-renew and differentiate into other non-stem cancer cells and resist traditional chemotherapy and radiotherapy.…”

Section: Colorectal Cancer Stem Cellsmentioning

confidence: 99%