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Chemo-resistance and metastasis are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator (phytohormone) whose biological effects on humans and animals has not yet been determined. In this study, we investigated the anticancer activity of this phytohormone on the drug resistant-triple negative breast cancer cell line MDA-MB-231. Treatment of the breast cancer cells with TDZ (1-50 [micro]mol/L) caused more stressful environment and induced a significant increase in active caspase-positive cells. In addition, TDZ treatment (5 and 10 [micro]mol/L) significantly attenuated the migration and the invasiveness of these highly metastatic cancer cells. Mechanistically, TDZ reduces cancer progression and invasiveness by targeting miR-202-5p, which stimulates the expression of phosphatase and tensin homo-log (PTEN), the tumor suppressor that downregulates the PI3K-Akt signaling pathway. Treatment with TDZ significantly upregulates miRNA-132, the suppressor of breast cancer proliferation, which is also implicated in dysregulation of the TEN-Akt-NF[kappa]B signaling pathway. Interestingly, our molecular docking analysis revealed a potential non-covalent interaction between TDZ and Akt, PTEN, and PI3K. These findings suggest that TDZ suppresses breast cancer metastasis by targeting miRNA-132, the miR-202-5p-PTEN axis, and the PI3K-Akt signaling pathway downstream. Key words: breast cancer, miR-132, PI3K-Akt signaling pathway, thidiazuron. Le développement de la chimiorésistance et des métastases constituent les causes les plus fréquentes de récidive et de décès par cancer du sein. Lethidiazuron (TDZ) est un régulateur de croissancedes plantes dont le rôle biologique sur les humains et les animaux n'a pas encore été clarifié. Dans la présente étude, les auteurs ont étudié l'activité anticancéreuse de cette phytohormone sur la lignée cellulaire de cancer du sein résistante aux médicaments et triple négative MDA-MB-231. Le traitement des cellulesdu cancerdu sein par le TDZ (1-50 [micro]mol/L) donnait lieu à un environnement plus stressant et induisait une augmentation significative du pourcentage de cellules positives aux caspases actives. En outre, le traitement au TDZ (5 et 10 [micro]mol/L) atténuait significativement la migration et l'invasion de ces cellules cancéreuses hautement métastatiques. Du point de vue de son mécanisme, le TDZ réduit la progression et l'invasion du cancer en ciblant le miR-202-5p qui stimule l'expression de la phosphatase PTEN, un suppresseur de tumeur qui régule négativement la voie de signalisation PI3K-Akt. En parallèle, le traitement au TDZ régule significativement à la hausse un suppresseur de la prolifération du cancer du sein, le miRNA-132, qui est également impliqué dans la dérégulation de la voie de signalisation de PTEN-Akt-NF[kappa]B. Il est intéressant de noter que cette analyse d'arrimage moléculaire a révélé une potentielle interaction non covalente entre le TDZ et Akt, la PTEN et la PI3K. Ces résultats suggèrent que le TDZ pourrait supprimer les métastases du cancer du sein en ciblant les molécules en aval miRNA-132, miR-202-5p-PTEN et PI3K-Akt. [Traduit par la Rédaction] Mots-clés : cancer du sein, miR-132, voie de signalisation PI3K-Akt, thidiazuron., Introduction Breast cancer is currently the second leading cause of cancer death worldwide, and the most frequently diagnosed tumor in women. Despite recent advances in early diagnosis and in understanding [...]

Sulforaphane (SPN) is reported to activate the Nrf2/Keap1 complex responsible for protein and gene expression promotion of various antioxidant enzymes. The present study examined the role of Nrf2 in modulating other signaling pathways involved in SPN's attenuation of acrolein (ACL)-induced cardiomyopathy in rats. Forty-two rat was categorized into seven 4-week treatment groups: control, SPN, losartan (LTN), ACL, ACL+SPN, ACL+LTN, and ACL+SPN+LTN. Heart samples were harvested for analysis; cardiac oxidative and injury biomarker levels and histopathological examination were undertaken. PPARγ, Nrf2, NF-κB, COX-2, and CYP2E1 protein expressions were examined. Results show that SPN and SPN+LTN reduced GSH, catalase, and lipid peroxidation compared to the ACL-treated group. Also, levels of creatine kinase-MB, cardiac troponin, and caspase 3 induced by ACL were all attenuated. Altered cardiac tissue pathophysiology by ACL was alleviated. SPN+LTN significantly increased Nrf2 expression via PPARγ action but decreased NF-κB and COX-2 expressions. Also, ACLincreased CYP2E1 expression was significantly attenuated by the SPN+LTN combination. For the first time, it suggests that SPN+LTN might offer a better therapeutic alternative to ACL-induced cardiomyopathy by activating Nrf2 via PPARγ and reducing NF-κB/COX-2/CYP2E1 expressions. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune, multifactorial, inflammatory disorder characterized by hyperplasia and infiltration of inflammatory cells at the synovial lining leading to destruction of cartilage and bone tissues. Pinocembrin (PCB) is a natural flavonoid extracted as a pure molecule from honey, propolis, and some plants. In this study, we evaluated the antiarthritic effect of PCB in adjuvant induced arthritis (AIA) mice. Treating the AIA mouse model with PCB reduced the arthritis symptoms/score, including edema size, extent of hind paw redness, abnormal movement, and holding inability. At the pathological level, PCB significantly decreased the joint erosion and percentages of infiltrated inflammatory cells. Biochemically, PCB interacts with the transcription factor, SRY-related HMG-box 4 (Sox4), and then modulates its dysregulated expression and the expression of Sox4/Stat3 signaling molecules in AIA mice. These molecules include tumor necrosis factor-α, nuclear transcription factor kappaB, and cyclooxygenase-2, besides the microRNAs; miR-132, miR-202-5p, and miR-7235, which are dysregulated in adjuvant-induced arthritis model relative to the control mice. The possible PCB interaction with Sox4 transcriptional protein was confirmed through molecular docking where three hydrogen bonds were formed at ARG and LYS residues at a stable binding energy of −4.72. Taken together, our data demonstrate that PCB could serve as a therapeutic drug in treatment of RA. [ABSTRACT FROM AUTHOR]

Essential oils have been used in various traditional healing systems since ancient times worldwide, due to their diverse biological activities. Several studies have demonstrated their plethora of biological activities—including anti-cancer activity—in a number of cell lines. Anisosciadium lanatum Boiss. is a perennial aromatic herb. Traditionally, it is an edible safe herb with few studies exploring its importance. The current study aims to investigate the chemical composition of essential oil isolated from Anisosciadium lanatum using GC-MS, as well as report its anti-cancer potential and its mechanistic effect on HepG2 liver cancer cell lines, and conduct molecular docking studies. To achieve this, the essential oil was isolated using a Clevenger apparatus and analyzed using GC-MS. The cell viability of HepG2 liver cancer and normal fibroblast NIH-3T3 cell lines was assessed by MTT cytotoxicity assay. The effects of the essential oil on cell migration and invasion were assessed using wound healing and matrigel assays, respectively. The effect of the essential oil on migration and apoptotic-regulating mRNA and proteins was quantified using quantitative real-time PCR and Western blot techniques, respectively. Finally, computational docking tools were used to analyze in silico binding of major constituents from the essential oil against apoptotic and migration markers. A total of 38 components were identified and quantified. The essential oil demonstrated regulation of cell proliferation and cell viability in HepG2 liver cancer cells at a sub-lethal dose of 10 to 25 μg/mL, and expressed reductions of migration and invasion. The treatment with essential oil indicated mitigation of cancer activity by aborting the mRNA of pro-apoptotic markers such as BCL-2, CASPASE-3, CYP-1A1, and NFκB. The algorithm-based binding studies demonstrated that eucalyptol, nerol, camphor, and linalool have potent binding towards the anti-apoptotic protein BCL-2. On the other hand, camphor and eucalyptol showed potent binding towards the pro-apoptotic protein CASPASE-3. These findings highlight the effectiveness of the essential oil isolated from Anisosciadium lanatum to drive alleviation of HepG2 cancer cell progression by modulating apoptotic markers. Our findings suggest that Anisosciadium lanatum could be used as a phytotherapeutic anti-cancer agent, acting through the regulation of apoptotic markers. More well-designed in vivo trials are needed in order to verify the obtained results. [ABSTRACT FROM AUTHOR]