BRM270 inhibits cancer stem cell maintenance via microRNA regulation in chemoresistant A549 lung adenocarcinoma cells

Kwon, Taeho; Chandimali, Nisansala; Huynh, Do Luong; Zhang, Jiao Jiao; Kim, Nameun; Bak, Yesol; Yoon, Do‐Young; Yu, Dae‐Yeul; Lee, Jae Cheol; Gera, Meeta; Ghosh, Mrinmoy; Park, Yang Ho

doi:10.1038/s41419-018-0277-7

Cited by 25 publications

(34 citation statements)

References 24 publications

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“…Clinical studies showed that the overexpression of IL-6 and Cox-2 contributes significantly to tumor growth [ 6 , 19 – 21 ] and blockades of IL-6 and Cox-2 signaling are potential chemotherapies [ 17 , 20 – 22 ]. Furthermore, our previous studies showed that BRM270, former version of KJS018A, enables suppressing tumor growth in lung adenocarcinoma [ 23 , 24 ]. Therefore, in this study we investigated inhibitory effects of KJS018A to hepatic tumor growth via xenografting SNU398 and HepG2 hepatic malignant cells in nude mice.…”

Section: Resultsmentioning

confidence: 99%

The Novel Nutraceutical KJS018A Prevents Hepatocarcinogenesis Promoted by Inflammation

Huynh

Chandimali

Zhang

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Inflammation is tightly associated with carcinogenesis at both the initiation and development of tumor. Many reports indicated that Cox-2 substantially contributes to inflammation and tumorigenesis. The novel nutraceutical KJS018A (BRM270 Function Enhanced Products) is the extract mixture from 8 herbal plants, which have been used to inhibit cancers and inflammation. The aim of the present study is to examine the inhibitory effects of KJS018A mixture to hepatocarcinogenesis and inflammation. The results showed that KJS018A significantly inhibited the proliferation of hepatic malignant cells and downregulated levels of IL-6 and Cox-2. Furthermore, KJS018A diminished the effect of PMA, an inflammatory inducer via IL-6/STAT3/Cox-2 pathway. Furthermore, KJS018A suppressed metastatic traits of hepatic malignant cells via downregulating Twist, N-cadherin, and MMP-9 while restoring E-cadherin expression. KJS018A also restrained tumor growth and levels of IL-6 and Cox-2 in immunohistochemistry staining. Taken together, these data suggest potential application of KJS018A in prevention of hepatocarcinogenesis promoted by inflammation.

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Section: Resultsmentioning

confidence: 99%

The Novel Nutraceutical KJS018A Prevents Hepatocarcinogenesis Promoted by Inflammation

Huynh

Chandimali

Zhang

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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“…It has been shown that in the gefitinib-resistant lung cancer PC9-CSCs, expression of miR-128 was markedly suppressed as compared to non-CSCs and upregulation of miR-128 reverses the gefitinib resistance of the lung cancer stem cells by inhibiting the c-met/PI3K/AKT pathway [72]. In another study, it was found that BRM270, an extract from seven plants, triggers the expression of miR-128 in lung CSCs and sensitized chemoresistant A549 lung cancer cells by attenuating lung CSC traits via inhibition of the activation of VEGF/PI3K/AKT signaling pathways [70]. Downregulation of miR-218 in lung cancer cells has been shown to induce constitutive activation of STAT3, which is critically associated with oncogenesis.…”

Section: Lung Cancermentioning

confidence: 99%

“…MiRNA-215 DTL [59] miR-148a WNT, β-catenin [60] miR-199a/b Gsk3β, Wnt/β-catenin-ABCG2 [61] miR-196b-5p STAT3 [62] miRs-31 EphB2 and EphA2 [63] miR-27a Apaf-1/caspase-9 [64] miR-372/373 Nanog, Hedgehog, NFκB, MAPK/Erk, VDR Jak-STAT, TGF-beta, PI3K-Akt, MAPK. [65,66] miR-137 DCLK1 [67] miR-146a β-catenin [68] miR-195-5p STAT3, BIRC5, BCL2, BCL-XL, SOX2, CD133, RBPJ, Notch2 [62,69] Lung miR-128 AKT/ERK, p38, c-met/PI3K/AKT, VEGF/PI3K/AKT, IL-6-JAK-STAT3 [70][71][72][73] miR-181b Notch2 [74] miR-138 TGFβ [75] miR-5100 Rab6 [76] miR-214 c-MYC [76] miR-708-5p Wnt/β-catenin [77] miR-873 miR-125a-3p…”

Section: Role Of Mirna and Oncogenic Signaling Pathways In Human Cancmentioning

confidence: 99%

Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies

Khan

Ahmed

Elareer

et al. 2019

Cells

237

168

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Recent biomedical discoveries have revolutionized the concept and understanding of carcinogenesis, a complex and multistep phenomenon which involves accretion of genetic, epigenetic, biochemical, and histological changes, with special reference to MicroRNAs (miRNAs) and cancer stem cells (CSCs). miRNAs are small noncoding molecules known to regulate expression of more than 60% of the human genes, and their aberrant expression has been associated with the pathogenesis of human cancers and the regulation of stemness features of CSCs. CSCs are the small population of cells present in human malignancies well-known for cancer resistance, relapse, tumorigenesis, and poor clinical outcome which compels the development of novel and effective therapeutic protocols for better clinical outcome. Interestingly, the role of miRNAs in maintaining and regulating the functioning of CSCs through targeting various oncogenic signaling pathways, such as Notch, wingless (WNT)/β-Catenin, janus kinases/ signal transducer and activator of transcription (JAK/STAT), phosphatidylinositol 3-kinase/ protein kinase B (PI3/AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-kB), is critical and poses a huge challenge to cancer treatment. Based on recent findings, here, we have documented the regulatory action or the underlying mechanisms of how miRNAs affect the signaling pathways attributed to stemness features of CSCs, such as self-renewal, differentiation, epithelial to mesenchymal transition (EMT), metastasis, resistance and recurrence etc., associated with the pathogenesis of various types of human malignancies including colorectal cancer, lung cancer, breast cancer, head and neck cancer, prostate cancer, liver cancer, etc. We also shed light on the fact that the targeted attenuation of deregulated functioning of miRNA related to stemness in human carcinogenesis could be a viable approach for cancer treatment.

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“…Lung cancer is the most common type of malignancy and leading cause of cancer-related mortality in the world [ 59 ]. Small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) are the two main histological types of lung cancers [ 60 ].…”

Section: Jnk Activation Is Induced By Aberrant Prx II Expression Imentioning

confidence: 99%

Peroxiredoxin II Regulates Cancer Stem Cells and Stemness-Associated Properties of Cancers

Chandimali

Jeong

Kwon

2018

Cancers

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Cancer stem cells (CSCs) represent a sub-population of cancer cells with the ability to regulate stemness-associated properties which are specifically responsible for unlimited growth of cancers, generation of diverse cancer cells in differentiated state and resistance to existing chemotherapy and radiotherapy. Even though, current therapies destroy majority of cancer cells, it is believed to leave CSCs without eradicating which may be the conceptualization for chemoresistance and radio-resistance. Reactive oxygen species (ROS) maintain stem cells and regulate the stemness-associated properties of cancers. Beyond the maximum limit, ROS can damage cellular functions of cancers by subjecting them to oxidative stress. Thus, maintenance of ROS level plays an important role in cancers to regulate stemness-associated properties. Peroxiredoxin II (Prx II) is a member of peroxiredoxin antioxidant enzyme family which considers as a regulator of ROS in cellular environments by modulating redox status to maintain CSC phenotype and stemness properties. Prx II has cell type-dependent expression in various types of cancer cells and overexpression or silenced expression of Prx II in cancers is associated with stem cell phenotype and stemness-associated properties via activation or deactivation of various signaling pathways. In this review, we summarized available studies on Prx II expression in cancers and the mechanisms by which Prx II takes parts to regulate CSCs and stemness-associated properties. We further discussed the potential therapeutic effects of altering Prx II expression in cancers for better anticancer strategies by sensitizing cancer cells and stem cells to oxidative stress and inhibiting stemness-associated properties.

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BRM270 inhibits cancer stem cell maintenance via microRNA regulation in chemoresistant A549 lung adenocarcinoma cells

Cited by 25 publications

References 24 publications

The Novel Nutraceutical KJS018A Prevents Hepatocarcinogenesis Promoted by Inflammation

The Novel Nutraceutical KJS018A Prevents Hepatocarcinogenesis Promoted by Inflammation

Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies

Peroxiredoxin II Regulates Cancer Stem Cells and Stemness-Associated Properties of Cancers

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