Pro-metastatic activity of AGR2 interrupts angiogenesis target bevacizumab efficiency via direct interaction with VEGFA and activation of NF-κB pathway.

Anterior gradient 2 (AGR2), an endoplasmic reticulum (ER)-resident protein-disulfide isomerase (PDI), is associated with cancer development and malignant progression. Here, we show that high level of AGR2 promotes the aggressive phenotype of prostate cancer (PCa) mouse models developed by either patient-derived xenografts or surgical intra-prostate implantation of PCa cells, associated with enrichment of the blood vessel network in tumor tissues. Angiogenesis markers VEGFR2 and CD34, accompanied with the invasive marker Vimentin, were predominantly stained in metastatic liver tissues.

Losartan protects against cerebral ischemia/reperfusion-induced apoptosis through β-arrestin1-mediated phosphorylation of Akt.

Losartan, an angiotensin (Ang) II type 1 receptor blocker (ARB), has been revealed to protect against cerebral ischemia/reperfusion (I/R) injury. However, the mechanism by which losartan protect brain ischemia injury is still obscure. In this study, we investigated whether losartan protected against cerebral I/R injury by reducing apoptosis and the possible signaling pathways.

Tetramethylpyrazine Analogue CXC195 Protects Against Dopaminergic Neuronal Apoptosis via Activation of PI3K/Akt/GSK3β Signaling Pathway in 6-OHDA-Induced Parkinson's Disease Mice.

Parkinson's disease (PD) is a progressive neurodegenerative disorder and characterized by motor system disorders resulting in loss of dopaminergic (DA) neurons. CXC195, a novel tetramethylpyrazine derivative, has been shown strongest neuroprotective effects due to its anti-apoptotic activity. However, whether CXC195 protects against DA neuronal damage in PD and the mechanisms underlying its beneficial effects are unknown.

Targeting autophagy augments the activity of DHA-E3 to overcome p-gp mediated multi-drug resistance.

Multidrug resistance (MDR) is a major obstacle for successful chemotherapy treatment. Searching for effective MDR modulators and combining them with anticancer drug therapies has been a promising strategy against clinical MDR. In our previous study, we have found that DHA-E3, a synthetic derivative of DHA, has the ability to modulate the function of P-glycoprotein (P-gp) and reverse MDR in cancer cells.

Jungermannenone A and B induce ROS- and cell cycle-dependent apoptosis in prostate cancer cells in vitro.

Aim: Jungermannenone A and B (JA, JB) are new ent-kaurane diterpenoids isolated from Chinese liverwort Jungermannia fauriana, which show anti-proliferation activities in cancer cells. In this study we investigated the mechanisms underlying the anticancer action of JA and JB in PC3 human prostate cancer cells in vitro.

Methods: A panel of 9 human cancer cell lines was tested.

Malformin A1 promotes cell death through induction of apoptosis, necrosis and autophagy in prostate cancer cells.

Purpose: Malformin A1 (MA1), a cyclopentapeptide isolated from fungal origin, has been identified to induce varieties of intriguing biological activities. Here, we reported the mode of mechanism underlying MA1-mediated cytotoxicity through induction of apoptosis, necrosis and autophagy in prostate cancer (PCa) cells.

Methods: Human PCa cells PC3 and LNCaP were treated with MA1, and cell viability, apoptosis, necrosis, mitochondrial damage, oxidative stress and autophagy were analyzed, respectively.

Bisbibenzyls, novel proteasome inhibitors, suppress androgen receptor transcriptional activity and expression accompanied by activation of autophagy in prostate cancer LNCaP cells.

Context: Bisbibenzyl compounds have gained our interests for their potential antitumor activity in malignant cell-types.

Objective: The objective of this study is to investigate the effect of bisbibenzyl compounds riccardin C (RC), marchantin M (MM), and riccardin D (RD) on androgen receptor (AR) in prostate cancer (PCa) cells.

Materials And Methods: After exposure to 10 μM of the compounds for 24 h, cell cycle and cell survival analyses were performed using FACS and MTT assay to confirm the effect of these bisbibenzyls on PCa LNCaP cells.

Regulation of SOD2 and β-arrestin1 by interleukin-6 contributes to the increase of IGF-1R expression in docetaxel resistant prostate cancer cells.

Although several mechanisms behind resistance to docetaxel in castration-refractory prostate cancer (CRPC) have been investigated, molecular determinants of evolved resistance are still not entirely understood. Proteomics-based analysis in this study revealed that SOD2, associated with downregulation of reactive oxygen species (ROS), was significantly up-regulated in docetaxel-resistant (PC3/Doc) cells if compared to sensitive cells, and the expression of redox-regulated genes such as IGF-1R, CXCR4, and BCL2 was increased as well. Forced expression of SOD2 in sensitive cells led to the increase of IGF-1R and association with drug resistance, whereas silencing of SOD2 resulted in the decrease of IGF-1R at the protein level in resistant cells.

DHA2, a synthesized derivative of bisbibenzyl, exerts antitumor activity against ovarian cancer through inhibition of XIAP and Akt/mTOR pathway.

The analysis of dihydroptychantol (DHA) and its chemically synthesized macrocyclic bisbibenzyl derivatives (DHA1, 2 and 3) led to the selection of DHA2 as a potential drug candidate for ovarian cancer. The exposure of ovarian cancer SKOV3 cells to DHA2 resulted in the downregulation of the anti-apoptotic X-linked inhibitor of apoptosis protein (XIAP) and Bcl-2 and led to caspase-independent cell death. The overexpression of XIAP reversed DHA2-induced cell death, and the depletion of XIAP had the opposite effect.

Anti-inflammatory effect of Marchantin M contributes to sensitization of prostate cancer cells to docetaxel.

As pro-inflammatory cytokines and chemokines contribute to the malignancy of many types of human cancer, we examined the anti-inflammatory effect of bisbibenzyls, a diverse bioactive group of naturally occurring compounds. Marchantin M (Mar M) was identified through a screening process of these compounds as a potent anti-inflammatory agent based on its capacity to inhibit LPS-induced IL6, IL1β and CCL2 expression in HUVECs and PBMCs without affecting cell proliferation. Since Mar M has been found to exhibit anticancer activity, we observed that Mar M treatment also resulted in decreases in the expressions of IL6, IL1β and TNFα in metastatic prostate cancer (PCa) cells.

Tetramethylpyrazine analogue CXC195 protects against cerebral ischemia/reperfusion-induced apoptosis through PI3K/Akt/GSK3β pathway in rats.

CXC195 showed strongest protective effects among the ligustrazine derivatives in cells and prevented apoptosis induced by H2O2 injury. We recently demonstrated that CXC195 protected against cerebral ischemia/reperfusion (I/R) injury by its antioxidant activity. However, whether the anti-apoptotic action of CXC195 is involved in cerebral I/R injury is unknown.

Toxoplasma gondii: immune response and protective efficacy induced by ROP16/GRA7 multicomponent DNA vaccine with a genetic adjuvant B7-2.

Toxoplasma gondii infection occurs commonly in humans and other warm-blooded animals. Its serious impact on public health and livestock sectors makes the development of an effective vaccine particularly important. In the current study, we constructed a multiantigenic DNA vaccine expressing ROP16 and GRA7 of T.

Riccardin D Exerts Its Antitumor Activity by Inducing DNA Damage in PC-3 Prostate Cancer Cells In Vitro and In Vivo.

We recently reported that Riccardin D (RD) was able to induce apoptosis by targeting Topo II. Here, we found that RD induced cell cycle arrest in G2/M phase in PC-3 cells, and caused remarkable DNA damage as evidenced by induction of γH2AX foci, micronuclei, and DNA fragmentation in Comet assay. Time kinetic and dose-dependent studies showed that ATM/Chk2 and ATR/Chk1 signaling pathways were sequentially activated in response to RD.