Uncoupling tumor necrosis factor-α and interleukin-10 at tumor immune microenvironment of breast cancer through miR-17-5p/MALAT-1/H19 circuit

Soliman, R.A.; Youness, R.A.; Manie, Tamer M.; Khallaf, Emad; El‐Shazly, Mohamed; AbdelMohsen, Mona M.; Handoussa, Heba

doi:10.32604/biocell.2022.016636

Cited by 13 publications

(15 citation statements)

References 65 publications

(61 reference statements)

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“…12 (2022) value (22.4± 0.64 µg/ml) on comparison with doxorubicin which exhibited IC 50 value (0.35± 0.036 µg/ml). Several pharmacological studies have demonstrated different pathways of ursolic acid to inhibit proliferation of breast tumor cells, induce apoptosis and autophagy of the cells without normal cell damage [33][34][35]. In this study, molecular docking revealed the potential of ursolic acid to bind at the active site of PT1B enzyme, a key player in breast cancer.…”

Section: Discussionmentioning

confidence: 72%

Identification and quantitation of ursolic acid in Plectranthus amboinicus extract; molecular docking approach for its antiproliferative potential

et al. 2022

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High performance liquid chromatography (HPLC) with UV detection has been employed for the quantitative determination of ursolic acid in the ethyl acetate extract of the aerial parts of Plectranthus amboinicus. The antiproliferative activity of the extract and ursolic acid against MCF-7 was tested in vitro by MTT assay. Molecular modeling using MOE was employed to check the binding mode of ursolic acid (UA) with the crystal structures of the Protein tyrosine phosphatase 1B (PTP1B) enzyme complexed with the orthosteric sulfamic acid inhibitor (PDB: 2F71). Ursolic acid was detected in the ethyl acetate extract at 203 nm with retention time 6.98 min and the HPLC analytical methodology for standard curve was developed and validated to quantify ursolic acid as 3.96 mg/g DW. The ursolic acid and extract were highly active against MCF-7 cell line with IC 50 22.4± 0.64 µg/ml and 43.1± 2.3 µg/ml respectively. Molecular study emphasized the influential ursolic acid fitting in the binding site of PTP1B enzyme suggesting its inhibition to be responsible for the in vitro anticancer activity. These findings justify the use of Plectranthus amboinicus against cancer and strengthen its selection for the discovery of natural anticancer agents. Also, the results provide important guidance for the potential pathway of ursolic acid as anticancer compound.

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Section: Discussionmentioning

confidence: 72%

Identification and quantitation of ursolic acid in Plectranthus amboinicus extract; molecular docking approach for its antiproliferative potential

et al. 2022

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“…Patients' resistance to immune checkpoint inhibitors appears to be caused by an unknown mechanism. Our research team recently identified a novel mechanism by which IL-10 and TNF-α reduce immune checkpoint inhibitors effectiveness in some individuals in an effort to unravel this mystery [11] . In the present study, we unlocked another piece in the puzzle by probing the cytotoxic potential of other cellular components at the TME of TNBC patients.…”

Section: Discussionmentioning

confidence: 99%

“…miR-34a was also found to induce the expression of another NKG2D ligand known as ULBP2 in melanoma cells [60] ; thus supporting the innate immune activator role of miR-34a in several oncological and non-oncological contexts. On the other hand, our research group has recently highlighted the immunomodulatory role of miR-17–5p in TNBC mainly through alleviating the immune suppressive TME upon dampening the release of IL-10 and TNF-α from TNBC cells at the TME [11] . Ohno et.al.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, our research group has focused on a hot-topic in the immunoncology field where we found that vital non-cellular components of the tumor microenvironment (TME) of TNBC patients such as IL-10 and TNF-α might pose as a barrier to immune checkpoint inhibitors efficiency in some patients [11] . However, in order to have the full picture we thought of a study to decipher the cellular components of the TME of TNBC patients as well.…”

Section: Introductionmentioning

confidence: 99%

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MALAT-1: Immunomodulatory lncRNA hampering the innate and the adaptive immune arms in triple negative breast cancer

Mekky

Ragab²,

Manie

et al. 2023

Translational Oncology

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“…Thus, the pharmacological inhibitors of H 2 S-synthesizing enzymes did not show consistent outcomes, due to selectivity and dose- and time-adjustment issues [ 85 ]. Accordingly, molecular genetics therapeutic tools such as microRNAs (miRNAs), short hairpin RNAs (shRNAs), and small interfering RNAs (siRNAs) provide promising approaches that would allow for the specific targeting of H 2 S-synthesizing enzymes [ 79 , 84 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 ]. The following part of the review focuses on the possible mechanisms through which such RNA-based molecular genetics targeting approaches could be used and delivered to brain tumors.…”

Section: Modern Rna-based Therapeutic Modalitiesmentioning

confidence: 99%

Molecular Engines, Therapeutic Targets, and Challenges in Pediatric Brain Tumors: A Special Emphasis on Hydrogen Sulfide and RNA-Based Nano-Delivery

Fahmy¹,

Dawoud

Zeinelabdeen

et al. 2022

Cancers

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Pediatric brain tumors represent a formidable challenge in the field of oncology. Pediatric brain tumors are sub-classified into several molecular sub-types, where each one is characterized by an array of hyperactivated oncogenic molecular engines. However, there have been great efforts dedicated to portray the involved signaling pathways driving pediatric brain tumors. Yet, a full understanding of the intertwined oncogenic pathways involved is still obscure. In this review, the authors shed light on novel therapeutic targets tailored for several sub-types of pediatric brain tumors and point out the limitations of such therapeutic approaches. Hydrogen Sulfide (H2S) has recently been cast as an oncogenic driver in several solid malignancies, yet its role in brain tumors is still under investigation. The authors also highlight the possible involvement of H2S in pediatric brain tumors and propose promising brain-delivery strategies for the sake of achieving better therapeutic results for brain tumors patients.Abstract: Pediatric primary brain tumors represent a real challenge in the oncology arena. Besides the psychosocial burden, brain tumors are considered one of the most difficult-to-treat malignancies due to their sophisticated cellular and molecular pathophysiology. Notwithstanding the advances in research and the substantial efforts to develop a suitable therapy, a full understanding of the molecular pathways involved in primary brain tumors is still demanded. On the other hand, the physiological nature of the blood–brain barrier (BBB) limits the efficiency of many available treatments, including molecular therapeutic approaches. Hydrogen Sulfide (H2S), as a member of the gasotransmitters family, and its synthesizing machinery have represented promising molecular targets for plentiful cancer types. However, its role in primary brain tumors, generally, and pediatric types, particularly, is barely investigated. In this review, the authors shed the light on the novel role of hydrogen sulfide (H2S) as a prominent player in pediatric brain tumor pathophysiology and its potential as a therapeutic avenue for brain tumors. In addition, the review also focuses on the challenges and opportunities of several molecular targeting approaches and proposes promising brain-delivery strategies for the sake of achieving better therapeutic results for brain tumor patients.

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Uncoupling tumor necrosis factor-α and interleukin-10 at tumor immune microenvironment of breast cancer through miR-17-5p/MALAT-1/H19 circuit

Cited by 13 publications

References 65 publications

Identification and quantitation of ursolic acid in Plectranthus amboinicus extract; molecular docking approach for its antiproliferative potential

Identification and quantitation of ursolic acid in Plectranthus amboinicus extract; molecular docking approach for its antiproliferative potential

MALAT-1: Immunomodulatory lncRNA hampering the innate and the adaptive immune arms in triple negative breast cancer

Molecular Engines, Therapeutic Targets, and Challenges in Pediatric Brain Tumors: A Special Emphasis on Hydrogen Sulfide and RNA-Based Nano-Delivery

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