7-Methoxyheptaphylline Enhances TRAIL-Induced Apoptosis of Colorectal Adenocarcinoma Cell via JNK-Mediated DR5 Expression.

A cytokine known as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has the ability to precisely cause the death of cancer cells, while normal cells are left undisturbed. Recent studies show that certain cancer cells are sensitive to the apoptotic effect of TRAIL. In this study, HT29 colorectal adenocarcinoma cells exposed to TRAIL were treated with heptaphylline and 7-methoxyheptaphylline from Clausena harmandiana in an effort to comprehend the mechanisms involved behind this activity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test was utilized to determine cell survival, and phase contrast microscopy was used to examine cell morphology. Through using real-time RT-PCR, Western blotting, and RT-PCR, the molecular mechanisms were investigated. According to the findings, whilst hepataphylline caused cytotoxicity in normal colon FHC cells, in comparison to healthy colon FHC cells, 7-methoxyheptaphylline inhibited cancer cells in a concentration-dependent manner. Heptaphylline alone or in conjunction with TRAIL showed no discernible effect on TRAIL-induced HT29 cell death, but 7-methoxyheptaphylline boosted caspase-3 cleavage. The study showed that the c-Jun N-terminal kinase (JNK) pathway was responsible for the 7-methoxyheptaphylline's enhancement of the death receptor 5 (DR5) mRNA, TRAIL receptor, and protein. The results demonstrated that the 7-methoxyheptaphylline of Clausena harmandiana increased the expression of DR5 via the JNK pathway, intensifying TRAIL-induced HT29 cell death.

The Effect of Ethanol Extract from Mesua ferrea Linn Flower on Alzheimer's Disease and Its Underlying Mechanism.

The effects of Mesua ferrea Linn flower (MFE) extract on the pathogenic cascade of Alzheimer's disease (AD) were determined by an in vitro and cell culture model in the search for a potential candidate for the treatment of AD. The 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay exhibited that the MFE extract had antioxidant activities. According to the Ellman and the thioflavin T method's result, the extracts could inhibit acetylcholinesterase and ß-amyloid (Aß) aggregation. Studies on neuroprotection in cell culture found that the MFE extract could reduce the death of human neuroblastoma cells (SH-SY5Y) caused by H2O2 and Aß. Western blot analysis exhibited that the MFE extract alleviated H2O2-induced neuronal cell damage by downregulating the pro-apoptotic proteins, including cleaved caspase-3, Bax, and by enhancing the expression of anti-apoptotic markers including MCl1, BClxl, and survivin. Moreover, MFE extract inhibited the expression of APP, presenilin 1, and BACE, and increased the expression of neprilysin. In addition, the MFE extract could enhance scopolamine-induced memory deficit in mice. Overall, results showed that the MFE extract had several modes of action related to the AD pathogenesis cascade, including antioxidants, anti-acetylcholinesterase, anti-Aß aggregation, and neuroprotection against oxidative stress and Aß. Therefore, the M. ferrea L. flower might be a possibility for further development as a medication for AD.

Neuroprotective and anticancer effects of 7­Methoxyheptaphylline via the TAK1 pathway.

7­Methoxyheptaphylline (7­MH) is a carbazole extracted from Clausena harmandiana, a medicinal plant that is used to treat headaches and stomachaches. The aim of the present study was to examine the neuroprotective effects and anticancer activity of 7­MH. Cell death was assessed using an MTT assay and flow cytometry. The expression of apoptosis­related proteins was determined by western blot analysis. An animal model was used to test anti­metastasis. The interactions between 7­MH and the molecular target were observed using molecular docking. The results revealed that 7­MH provided protection against hydrogen peroxide (H2O2)­induced neuronal cell death. In cancer cells, 7­MH induced SH­SY5Y, 4T1, HT29, HepG2, and LNCaP cell death. 7­MH inhibited metastasis of HT29 cells in vitro and 4T1­Luc cells in vitro and in vivo. 7­MH inhibited proteins, including P­glycogen synthase kinase (GSK)­3, and cleaved caspase­3, but it activated anti­apoptotic proteins in H2O2­induced SH­SY5Y cell death. By contrast, 7­MH activated the cleaving of caspase­3 and GSK­3, but it suppressed anti­apoptotic proteins in SH­SY5Y cells. 7­MH reduced the levels of NF­κB and STAT3 in 4T1 cells; phospho­p65, Erk, and MAPK13 in LNCaP cells; and phospho­Erk and matrix metalloproteinase­9 in HT29 cells. Molecular docking analysis showed that 7­MH targets TAK1 kinase. The present study indicated that 7­MH induced apoptosis of cancer cells and provided protection against H2O2­induced neuron cell death via TAK1 kinase.

Acridone Derivatives from Atalantia monophyla Inhibited Cancer Cell Proliferation through ERK Pathway.

The present study aimed to investigate the effect of acridone alkaloids on cancer cell lines and elucidate the underlying molecular mechanisms. The ten acridone alkaloids from Atalantia monophyla were screened for cytotoxicity against LNCaP cell lines by a WST-8 assay. Then, the most potential acridone, buxifoliadine E, was evaluated on four types of cancer cells, namely prostate cancer (LNCaP), neuroblastoma (SH SY5Y), hepatoblastoma (HepG2), and colorectal cancer (HT29). The results showed that buxifoliadine E was able to significantly inhibit the proliferation of all four types of cancer cells, having the most potent cytotoxicity against the HepG2 cell line. Western blotting analysis was performed to assess the expression of signaling proteins in the cancer cells. In HepG2 cells, buxifoliadine E induced changes in the levels of Bid as well as cleaved caspase-3 and Bax through MAPKs, including Erk and p38. Moreover, the binding interaction between buxifoliadine E and Erk was investigated by using the Autodock 4.2.6 and Discovery Studio programs. The result showed that buxifoliadine E bound at the ATP-binding site, located at the interface between the N- and C-terminal lobes of Erk2. The results of this study indicate that buxifoliadine E suppressed cancer cell proliferation by inhibiting the Erk pathway.

Nordentatin Inhibits Neuroblastoma Cell Proliferation and Migration through Regulation of GSK-3 Pathway.

Cancer is caused by abnormal cell changes leading to uncontrolled cell growth. The specific characteristics of cancer cells, including the loss of apoptotic control and the ability to migrate into and invade the surrounding tissue, result in cancer cell metastasis to other parts of the body. Therefore, the inhibition of the proliferation, migration, and invasion of cancer cells are the principal goals in the treatment of cancer. This study aimed to investigate the inhibitory activity of nordentatin, a coumarin derivative isolated from Clausena harmandiana, regarding the proliferation and migration of human neuroblastoma cells (SH-SY5Y). Nordentatin at a concentration of 100 µM showed cell cytotoxicity toward SH-SY5Y that was significantly different from that of the control group (p < 0.01) at 24, 48, and 72 h. Moreover, nordentatin inhibited SH-SY5Y proliferation by inhibiting the antiapoptotic protein Mcl-1, leading to the cleavage of caspase-3 and resulting in the inhibition of a migratory protein, MMP-9, through the GSK-3 pathway (compared with cells treated with a GSK inhibitor). These results suggest that nordentatin inhibited the proliferation and migration of neuroblastoma cells through the GSK-3 pathway.