Oridonin triggers G2/M cell cycle arrest, cellular apoptosis and autophagy in human gastric cancer cells
Liver cancer is of the devastating human cancers and its incidence is increasing at an alarming rate. The clinical outcomes are far from descent due to lack of efficient therapeutic targets and chemotherapeutic agents. Studies have revealed the therapeutic implications of microRNAs in the management of different human cancers. This study was designed to explore the role and therapeutic potential of miR-638 in liver cancer via modulation of zeste homolog 2 (EZH2). The results revealed significant (P < 0.05) downregulation of miR-638 in human liver cancer tissues and cell lines.
Overexpression of miR-638 led to a significant (P < 0.05) decline in liver cancer cell proliferation. Nonetheless, inhibition of miR-638 could promote the proliferation of the human liver cancer cells. The DAPI and annexin V/PI staining assays revealed that miR-638 induces apoptosis in human liver cancer cells which was accompanied by enhancement of Bax and depletion of Bcl-2 expression. Furthermore, miR-638 overexpression also leads to a significant (P < 0.05) increase of autophagosomes and autolysosomes in liver cancer cells suggestive of autophagy. The induction of autophagy was further confirmed by increase and decrease in expression of LC3B-II and Beclin-1 proteins, respectively. In contrary, inhibition of miR-638 prevented both apoptosis and autophagy of the liver cancer cells. In silico analysis and the dual luciferase assay revealed EZH2 as the molecular target of miR-638 at post-transcriptional level. The qRT-PCR showed that EZH2 to be significantly (P < 0.05) upregulated in the human liver cancer tissues and cell lines.
However, the expression of EZH2 was considerably suppressed upon miR-638 overexpression in SNU-423 cells. Taken together, these findings suggest the tumor-suppressive role of miR-638/EZH2 axis liver cancer and point towards the potential of miR-638 as therapeutic target in the treatment of liver cancer. WST-1 assay was used to determine cell viability. The fact that ambrosin induced apoptosis was studied through acridine orange (AO)/ethidium bromide (EB) staining using fluorescence microscopy as well as using flow cytometry in association with annexin-v/propidium iodide (PI) staining. Furthermore, western blot assay was used to study effects of ambrosin on apoptosis-related protein expressions including Bax and Bcl-2, as well as to study the effects on numerous caspases and Akt/β-Catenin Signaling Pathway. The effects on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were evaluated by flow cytometry.
A Logic AND-Gated Sonogene Nanosystem for Precisely Regulating the Apoptosis of Tumor Cells
To date, many methods have been developed for inducing tumor cell death, such as using chemical drugs and radiation. However, all of them have a common problem, a lack of mechanisms for precisely regulating the death of tumor cells. It often leads to nonspecific death and systemic side effects. Therefore, the efficacy and further application of these traditional methods are limited. In this paper, a logic AND-gated sonogene nanosystem was designed for precisely regulating the apoptosis of tumor cells. The running of this system required two essential parts, MscL I92L channel protein and ultrasound. Ultrasound could open the MscL I92L protein channel which when expressed on cells triggers the influx and outflux of small molecules through the channel. When the channel is kept open for a long time, Ca2+ influx becomes excessive which in turn activates the Ca2+ apoptosis pathway of cells.
The expression of MscL I92L protein and the applying of ultrasound constituted the logic AND gate which could implement the precise regulation to apoptosis. This strategy would help reduce nonspecific triggers and side effects. In this system, cationic nanoliposomes were prepared as the carrier for effectively delivering MscL I92L plasmids to tumor cells in vivo. We investigated the apoptosis-promoting effect of this system in different tumor cell lines (HeLa, B16, and 4T1). The results demonstrated that the apoptosis rate was highest in the B16 cell line (the early apoptosis rate was 11.9% and the late apoptosis rate was 59.1%) when the cells were subjected to consistent ultrasound (6 MHz, 15 W) for 30 min. This logic AND-gated sonogene nanosystem is expected to provide a new strategy and development direction for tumor therapy.
Anacardic 6-pentadecyl salicylic acid induces apoptosis in breast cancer tumor cells, immunostimulation in the host and decreases blood toxic effects of taxol in an animal model
Many antineoplastic agents induce myelosuppression and leukopenia as secondary effects in patients. The development of anticancer agents that simultaneously provoke antitumor immune response represents an important therapeutic advance. The administration of 6-pentadecyl salicylic acid (6SA) contributes to the antitumor immunity using 4 T1 breast cancer cells in Balb/c female mice, with Taxol as a positive control and in cotreatment with 6SA (6SA + Taxol; CoT). Our results show that 6SA reduces tumor volume and size by inducing caspase-8-mediated apoptosis without reducing tumor infiltrated lymphocytes. Also, 6SA reduced lung metastasis and increased the proportion of immune cells in blood, lymph nodes and bone marrow; more evidently, in the proportion of tumor-infiltrated natural killer (NK) cells and cytotoxic T lymphocytes.
Goat Anti Human Lambda Light Chain Polyclonal Antibody
Goat Anti-Human lambda ( chain specific) was previously known under catalogue number 25-787-278190 was previously known under catalogue number 25-787-278190
Goat Anti-Human lambda ( chain specific) was previously known under catalogue number 25-787-278185 was previously known under catalogue number 25-787-278185
Goat Anti-Human lambda ( chain specific) was previously known under catalogue number 25-787-278192 was previously known under catalogue number 25-787-278192
Taxol reduces helper and cytotoxic lymphocytes causing systemic immunosuppression and myelosuppression in bone marrow, whereas 6SA does not decrease any immune cell subpopulations in circulating blood and lymph nodes. More importantly, the CoT decreased the Taxol-induced cytotoxicity in circulating T cells and bone marrow. Treatment with 6SA increases the secretion of IL-2, IL-12, GM-CSF, TNF-α and IFN-γ and significantly reduces IL-10 and IL-17 secretion, suggesting that the reduction of regulatory T cells and tumor-associated macrophages contribute to the host control of tumor development. Finally, 6SA has an effective antineoplastic activity against breast cancer cells in an immunocompetent animal, reduces the myelosuppression and leukopenia that Taxol produces, improves the antitumoral immunological microenvironment and increases the overall survival of the animals improving the quality of life of patients with cancer.