Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

Son, Seung Wan; Lee, Han Yeoung; Moeng, Sokviseth; Kuh, Hyo-Jeong; Choi, Soo Young; Park, Jong Kook

doi:10.3390/molecules25204701

Cited by 13 publications

(10 citation statements)

References 327 publications

(375 reference statements)

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“…Regulation of functions and other genes during protein synthesis is regulated by miRNA. A number of phytochemicals have been described as molecules that efficiently affect miRNAs activity in the processes of carcinogenesis [ 82 , 83 , 84 ]. Numerous miRNAs have been applied as valid biomarkers in breast cancer diagnosis and prognosis.…”

Section: Discussionmentioning

confidence: 99%

Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

Kubatka

Kello

Kajo

et al. 2020

IJMS

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Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters–ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro.

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Section: Discussionmentioning

confidence: 99%

Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

Kubatka

Kello

Kajo

et al. 2020

IJMS

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“…Moreover, since the efficacy of anti-cancer treatments is affected by the level of ncRNAs [ 21 , 22 , 277 ], the combination of anti-cancer drugs with ncRNA-based therapy can further improve the therapeutic responses. For example, the effect of simvastatin on the repression of cell survival and metastasis is enhanced by the combined inhibition of miR-21 [ 278 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, miR-181a-5p can promote anoikis via repressing autophagy in normal mammary epithelial cells [ 20 ]. Besides, both miRNAs and lncRNAs can be differently expressed and modulate signaling pathways involved in multitudinous events, such as apoptotic cell death and metastasis in cancer [ 18 , 19 , 21 , 22 , 23 ]. A better understanding of the mechanisms underlying anoikis resistance and anchorage-independent growth can offer new opportunities to establish treatment strategies to control cancer.…”

Section: Introductionmentioning

confidence: 99%

The Role of Noncoding RNAs in the Regulation of Anoikis and Anchorage-Independent Growth in Cancer

Lee

Son

Moeng

et al. 2021

IJMS

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Cancer is a global health concern, and the prognosis of patients with cancer is associated with metastasis. Multistep processes are involved in cancer metastasis. Accumulating evidence has shown that cancer cells acquire the capacity of anoikis resistance and anchorage-independent cell growth, which are critical prerequisite features of metastatic cancer cells. Multiple cellular factors and events, such as apoptosis, survival factors, cell cycle, EMT, stemness, autophagy, and integrins influence the anoikis resistance and anchorage-independent cell growth in cancer. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are dysregulated in cancer. They regulate cellular signaling pathways and events, eventually contributing to cancer aggressiveness. This review presents the role of miRNAs and lncRNAs in modulating anoikis resistance and anchorage-independent cell growth. We also discuss the feasibility of ncRNA-based therapy and the natural features of ncRNAs that need to be contemplated for more beneficial therapeutic strategies against cancer.

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“…Moreover, ncRNAs can regulate the cancer microenvironment, contributing to disease progression and therapeutic resistance [ 227 ]. A ncRNA-based therapy through the depletion or restoration of ncRNAs has been perceived to strikingly boost the effects of anti-cancer treatments in cancer [ 228 , 229 ]. Moreover, experimental evidence presented here demonstrated that ncRNA-based therapy is a potential strategy to surmount the therapeutic resistance of currently available treatments, such as chemotherapy and radiation therapy, in PaC.…”

Section: Discussionmentioning

confidence: 99%

Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer

et al. 2021

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Therapeutic resistance is an inevitable impediment towards effective cancer therapies. Evidence accumulated has shown that the signaling pathways and related factors are fundamentally responsible for therapeutic resistance via regulating diverse cellular events, such as epithelial-to-mesenchymal transition (EMT), stemness, cell survival/apoptosis, autophagy, etcetera. Noncoding RNAs (ncRNAs) have been identified as essential cellular components in gene regulation. The expression of ncRNAs is altered in cancer, and dysregulated ncRNAs participate in gene regulatory networks in pathological contexts. An in-depth understanding of molecular mechanisms underlying the modulation of therapeutic resistance is required to refine therapeutic benefits. This review presents an overview of the recent evidence concerning the role of human ncRNAs in therapeutic resistance, together with the feasibility of ncRNAs as therapeutic targets in pancreatic cancer.

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Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

Cited by 13 publications

References 327 publications

Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

The Role of Noncoding RNAs in the Regulation of Anoikis and Anchorage-Independent Growth in Cancer

Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer

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