scholarly journals Asiatic Acid Induces Endoplasmic Reticulum Stress and Activates the Grp78/IRE1α/JNK and Calpain Pathways to Inhibit Tongue Cancer Growth

2021 ◽  
Vol 12 ◽  
Author(s):  
Jialin Li ◽  
Kan Chen ◽  
Jianhua Huang ◽  
Dongqing Chu ◽  
Miaomiao Tian ◽  
...  

Asiatic acid (AA) has been shown to induce apoptotic death in a range of cancers, but the mechanisms whereby it can inhibit tongue cancer growth have yet to be clarified. Herein, we explored the effects of AA on tongue cancer cells and found that it induced their apoptotic death in vitro and in vivo, while additionally impairing xenograft tumor growth in vivo. From a mechanistic perspective, AA treatment was associated with increases in levels of calcium and the calcium- dependent protease calpain, and it further induced endoplasmic reticulum (ER) stress and consequent Grp78-related IRE1α and JNK phosphorylation, ultimately driving caspase-3 activation and apoptotic death. Together, these results highlight AA as a promising tool for the therapeutic treatment of tongue cancer in clinical practice.

2014 ◽  
Vol 54 (11) ◽  
pp. 1417-1429 ◽  
Author(s):  
Chandagirikoppal V. Kavitha ◽  
Anil K. Jain ◽  
Chapla Agarwal ◽  
Angela Pierce ◽  
Amy Keating ◽  
...  

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Makoto Isono ◽  
Akinori Sato ◽  
Kazuki Okubo ◽  
Takako Asano ◽  
Keiichi Ito ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.


Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1459
Author(s):  
Tatiana N. Zamay ◽  
Vladimir S. Prokopenko ◽  
Sergey S. Zamay ◽  
Kirill A. Lukyanenko ◽  
Olga S. Kolovskaya ◽  
...  

Magnetomechanical therapy is one of the most perspective directions in tumor microsurgery. According to the analysis of recent publications, it can be concluded that a nanoscalpel could become an instrument sufficient for cancer microsurgery. It should possess the following properties: (1) nano- or microsized; (2) affinity and specificity to the targets on tumor cells; (3) remote control. This nano- or microscalpel should include at least two components: (1) a physical nanostructure (particle, disc, plates) with the ability to transform the magnetic moment to mechanical torque; (2) a ligand—a molecule (antibody, aptamer, etc.) allowing the scalpel precisely target tumor cells. Literature analysis revealed that the most suitable nanoscalpel structures are anisotropic, magnetic micro- or nanodiscs with high-saturation magnetization and the absence of remanence, facilitating scalpel remote control via the magnetic field. Additionally, anisotropy enhances the transmigration of the discs to the tumor. To date, four types of magnetic microdiscs have been used for tumor destruction: synthetic antiferromagnetic P-SAF (perpendicular) and SAF (in-plane), vortex Py, and three-layer non-magnetic–ferromagnet–non-magnetic systems with flat quasi-dipole magnetic structures. In the current review, we discuss the biological effects of magnetic discs, the mechanisms of action, and the toxicity in alternating or rotating magnetic fields in vitro and in vivo. Based on the experimental data presented in the literature, we conclude that the targeted and remotely controlled magnetic field nanoscalpel is an effective and safe instrument for cancer therapy or theranostics.


Author(s):  
Changhong Li ◽  
Kui Zhang ◽  
Guangzhao Pan ◽  
Haoyan Ji ◽  
Chongyang Li ◽  
...  

Abstract Background Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated. Methods In this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo. Results Our findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models. Conclusions Collectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.


Author(s):  
Domenico Mattoscio ◽  
Elisa Isopi ◽  
Alessia Lamolinara ◽  
Sara Patruno ◽  
Alessandro Medda ◽  
...  

Abstract Background Innovative therapies to target tumor-associated neutrophils (PMN) are of clinical interest, since these cells are centrally involved in cancer inflammation and tumor progression. Resolvin D1 (RvD1) is a lipid autacoid that promotes resolution of inflammation by regulating the activity of distinct immune and non-immune cells. Here, using human papilloma virus (HPV) tumorigenesis as a model, we investigated whether RvD1 modulates PMN to reduce tumor progression. Methods Growth-curve assays with multiple cell lines and in vivo grafting of two distinct HPV-positive cells in syngeneic mice were used to determine if RvD1 reduced cancer growth. To investigate if and how RvD1 modulates PMN activities, RNA sequencing and multiplex cytokine ELISA of human PMN in co-culture with HPV-positive cells, coupled with pharmacological depletion of PMN in vivo, were performed. The mouse intratumoral immune cell composition was evaluated through FACS analysis. Growth-curve assays and in vivo pharmacological depletion were used to evaluate anti-tumor activities of human and mouse monocytes, respectively. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was exploited to validate experimental findings in patients. Results RvD1 decreased in vitro and in vivo proliferation of human and mouse HPV-positive cancer cells through stimulation of PMN anti-tumor activities. In addition, RvD1 stimulated a PMN-dependent recruitment of classical monocytes as key determinant to reduce tumor growth in vivo. In human in vitro systems, exposure of PMN to RvD1 increased the production of the monocyte chemoattractant protein-1 (MCP-1), and enhanced transmigration of classical monocytes, with potent anti-tumor actions, toward HPV-positive cancer cells. Consistently, mining of immune cells infiltration levels in cervical cancer patients from the TCGA database evidenced an enhanced immune reaction and better clinical outcomes in patients with higher intratumoral monocytes as compared to patients with higher PMN infiltration. Conclusions RvD1 reduces cancer growth by activating PMN anti-cancer activities and encouraging a protective PMN-dependent recruitment of anti-tumor monocytes. These findings demonstrate efficacy of RvD1 as an innovative therapeutic able to stimulate PMN reprogramming to an anti-cancer phenotype that restrains tumor growth.


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