Targeting cancer stem cell-specific markers and/or associated signaling pathways for overcoming cancer drug resistance

Ranji, Peyman; Kesejini, Tayyebali Salmani; Saeedikhoo, Sara; Alizadeh, Ali Mohammad

doi:10.1007/s13277-016-5294-5

Cited by 32 publications

(21 citation statements)

References 122 publications

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“…From this perspective, the specific targeting of CSCs, together with conventional chemotherapy or radiotherapy, may achieve stable remission or cure cancer. 43, 44 Auffinger et al 45 showed that therapeutic doses of TMZ consistently increased the glioma stem cells (GSC) pool both in vitro and in vivo , and provided the first evidence that chemotherapeutic agents can able to interconvert between non-GSCs and GSCs. Recent study of their group revealed this conversion of glioma cells dedifferentiation to glioma stem-like cells was attributed to the therapeutic TMZ stress-induced HIF signaling.…”

Section: Discussionmentioning

confidence: 99%

Connective tissue growth factor promotes temozolomide resistance in glioblastoma through TGF-β1-dependent activation of Smad/ERK signaling

Zeng¹,

Zhao²,

Xu³

et al. 2017

Cell Death Dis

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Limited benefits and clinical utility of temozolomide (TMZ) for glioblastoma (GB) are frequently compromised by the development of acquired drug resistance. Overcoming TMZ resistance and uncovering the underlying mechanisms are challenges faced during GB chemotherapy. In this study, we reported that connective tissue growth factor (CTGF) was associated with GB chemoresistance and significantly upregulated in TMZ-treated GB cells. CTGF knockdown promoted TMZ-induced cell apoptosis and enhanced chemosensitivity, whereas its overexpression markedly conferred TMZ resistance in vitro and in vivo. Moreover, CTGF promoted TMZ resistance through stem-like properties acquisition and CD44 interference reversed the CTGF-induced TMZ resistance. Mechanistically, further investigation revealed that the TMZ-induced CTGF upregulation was tissue growth factor (TGF-β) dependent, and regulated by TGF-β1 activation through Smad and ERK1/2 signaling. Together, our results suggest a pivotal role of CTGF-mediated TMZ resistance through TGF-β1-dependent activation of Smad/ERK signaling pathways. These data provide us insights for identifying potential targets that are beneficial for overcoming TMZ resistance in GB.

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Section: Discussionmentioning

confidence: 99%

Connective tissue growth factor promotes temozolomide resistance in glioblastoma through TGF-β1-dependent activation of Smad/ERK signaling

Zeng¹,

Zhao²,

Xu³

et al. 2017

Cell Death Dis

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“…According to the results of IC 50 evaluation, an RCC cell line demonstrating resistance to sunitinib, termed 786-O/S, was generated by serial treatment of the parental 786-O cell line with various concentrations of sunitinib from 2.5 to 10 µM at 37˚C with the dose given at 1 month intervals. Following continuous culture in the complete medium supplemented with 10 µM sunitinib for >10 passages, identify the IC 50 of 786O/S cells with method mentioned above (concentrations of sunitinib, 5,10,15,20,30,40 and 50 µM). The cells were employed as sunitinib-resistant RCC cells in all subsequent experiments.…”

Section: Determination Of the Half-inhibitory Concentration (Ic 50 ) mentioning

confidence: 99%

“…CSCs express several specific markers that may facilitate the isolation and identification of CSCs, including cluster of differentiation (CD) 133, which is widely expressed (14). CD133, also termed prominin 1, is a 120 kDa transmembrane glycoprotein that is recognized as a useful marker for the identification and isolation of CSCs from many types of solid tumors, including colon, brain, lung, liver, prostate, skin and kidney cancer (15).…”

Section: Introductionmentioning

confidence: 99%

Significance of cyclooxygenase‑2, prostaglandin E2 and CD133 levels in sunitinib‑resistant renal cell carcinoma

et al. 2019

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The current study investigated the mechanism underlying sunitinib resistance. The parental human renal cell carcinoma (RCC) cell line 786-O was continuously exposed to various doses of sunitinib to obtain sunitinib-resistant cells (786-O/S). Cell proliferation and colony formation assays were performed to assess the survival of 786-O/S cells. The half-inhibitory concentration for the drug-resistant cells was calculated. 786-O/S cells demonstrated notably morphological changes compared with parental cells. Compared with 786-O cells, 786-O/S cells exhibited stronger proliferative and colony-forming abilities. Western blot analysis was performed to measure the levels of cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of COX-2 and cluster of differentiation (CD) 133 in both 786-O and 786-O/S cells. Following incubation of the two cell lines with celecoxib, a COX-2 inhibitor, RT-qPCR was performed to detect the expression of COX-2 and CD133, and western blot analysis was used to assess the expression of CD133. The results revealed that the levels of COX-2 and PGE2 were significantly higher in 786-O/S cells compared with 786-O cells (P<0.01). Similarly, the expression of CD133 was 24-fold higher in 786-O/S compared with the parental cells (P<0.01). When celecoxib was incubated with the two cell lines, the expression of COX-2 and CD133 decreased significantly (P<0.0001). In summary, the results indicate that activation of the COX-2-PGE2 pathway in RCC leads to the development of sunitinib resistance and may serve an important role in the maintenance of the characteristics of stem cells that are closely associated with drug resistance.

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“…While much of the discussion has been towards genetic changes within the tumor and that different cells may have different mutations, one has to wonder whether there are also epigenetic mechanisms that are seen in the cells within the tumor and if this is different depending on the immediate microenvironment of the tumor cells. One such cell that could be a real problem is the CSC, which is potentially the cause for treatment failure, drug resistance, metastasis and recurrence after surgery, chemotherapy as well as radiotherapy[206]. We [9] have learned that CSCs might have signaling pathways that are potentially unique to them such as Wnt/β-catenin, and Notch etc.…”

Section: Discussionmentioning

confidence: 99%

Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy

Dandawate

Subramaniam

Jensen

et al. 2016

Seminars in Cancer Biology

264

154

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Breast cancer is the most common form of cancer diagnosed in women worldwide and the second leading cause of cancer-related deaths in the USA. Despite the development of newer diagnostic methods, selective as well as targeted chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy, breast cancer recurrence, metastasis and drug resistance are still the major problems for breast cancer. Emerging evidence suggest the existence of cancer stem cells (CSCs), a population of cells with the capacity to self-renew, differentiate and be capable of initiating and sustaining tumor growth. In addition, CSCs are believed to be responsible for cancer recurrence, anticancer drug resistance, and metastasis. Hence, compounds targeting breast CSCs may be better therapeutic agents for treating breast cancer and control recurrence and metastasis. Naturally occurring compounds, mainly phytochemicals have gained immense attention in recent times because of their wide safety profile, ability to target heterogeneous populations of cancer cells as well as CSCs, and their key signaling pathways. Therefore, in the present review article, we summarize our current understanding of breast CSCs and their signaling pathways, and the phytochemicals that affect these cells including curcumin, resveratrol, tea polyphenols (epigallocatechin-3-gallate, epigallocatechin), sulforaphane, genistein, indole-3-carbinol, 3, 3′-diindolylmethane, vitamin E, retinoic acid, quercetin, parthenolide, triptolide, 6-shogaol, pterostilbene, isoliquiritigenin, celastrol, and koenimbin. These phytochemicals may serve as novel therapeutic agents for breast cancer treatment and future leads for drug development.

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Targeting cancer stem cell-specific markers and/or associated signaling pathways for overcoming cancer drug resistance

Cited by 32 publications

References 122 publications

Connective tissue growth factor promotes temozolomide resistance in glioblastoma through TGF-β1-dependent activation of Smad/ERK signaling

Connective tissue growth factor promotes temozolomide resistance in glioblastoma through TGF-β1-dependent activation of Smad/ERK signaling

Significance of cyclooxygenase‑2, prostaglandin E2 and CD133 levels in sunitinib‑resistant renal cell carcinoma

Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy

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