Cucurbitacin B and I inhibits colon cancer growth by targeting the Notch signaling pathway.

Cancer stem cells (CSCs) have the ability to self-renew and induce drug resistance and recurrence in colorectal cancer (CRC). As current chemotherapy doesn't eliminate CSCs completely, there is a need to identify novel agents to target them. We investigated the effects of cucurbitacin B (C-B) or I (C-I), a natural compound that exists in edible plants (bitter melons, cucumbers, pumpkins and zucchini), against CRC.

Diphenylbutylpiperidine Antipsychotic Drugs Inhibit Prolactin Receptor Signaling to Reduce Growth of Pancreatic Ductal Adenocarcinoma in Mice.

Background & Aims: Prolactin (PRL) signaling is up-regulated in hormone-responsive cancers. The PRL receptor (PRLR) is a class I cytokine receptor that signals via the Janus kinase (JAK)-signal transducer and activator of transcription and mitogen-activated protein kinase pathways to regulate cell proliferation, migration, stem cell features, and apoptosis. Patients with pancreatic ductal adenocarcinoma (PDAC) have high plasma levels of PRL.

Targeting transcription factor TCF4 by γ-Mangostin, a natural xanthone.

Given that colon cancer is the third most common cancer in incidence and cause of death in the United States, and current treatment modalities are insufficient, there is a need to develop novel agents. Towards this, here we focus on γ-Mangostin, a bioactive compound present in the Mangosteen () fruit. γ-Mangostin suppressed proliferation and colony formation, and induced cell cycle arrest and apoptosis of colon cancer cell lines.

The Histone Demethylase KDM3A, Increased in Human Pancreatic Tumors, Regulates Expression of DCLK1 and Promotes Tumorigenesis in Mice.

Background & Aims: The histone lysine demethylase 3A (KDM3A) demethylates H3K9me1 and H3K9Me2 to increase gene transcription and is upregulated in tumors, including pancreatic tumors. We investigated its activities in pancreatic cancer cell lines and its regulation of the gene encoding doublecortin calmodulin-like kinase 1 (DCLK1), a marker of cancer stem cells.

Methods: We knocked down KDM3A in MiaPaCa-2 and S2-007 pancreatic cancer cell lines and overexpressed KDM3A in HPNE cells (human noncancerous pancreatic ductal cell line); we evaluated cell migration, invasion, and spheroid formation under hypoxic and normoxic conditions.

Super-enhancers: novel target for pancreatic ductal adenocarcinoma.

Super-enhancers (SEs) are unique areas of the genome which drive high-level of transcription and play a pivotal role in the cell physiology. Previous studies have established several important genes in cancer as SE-driven oncogenes. It is likely that oncogenes may hack the resident tissue regenerative program and interfere with SE-driven repair networks, leading to the specific pancreatic ductal adenocarcinoma (PDAC) phenotype.

Metastatic Tumor-in-a-Dish, a Novel Multicellular Organoid to Study Lung Colonization and Predict Therapeutic Response.

Metastasis is a major cause of cancer-related deaths. A dearth of preclinical models that recapitulate the metastatic microenvironment has impeded the development of therapeutic agents that are effective against metastatic disease. Because the majority of solid tumors metastasize to the lung, we developed a multicellular lung organoid that mimics the lung microenvironment with air sac-like structures and production of lung surfactant protein.

MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells.

Quinomycin A targets Notch signaling pathway in pancreatic cancer stem cells.

Cancer stem cells (CSCs) appear to explain many aspects of the neoplastic evolution of tumors and likely account for enhanced therapeutic resistance following treatment. Dysregulated Notch signaling, which affects CSCs plays an important role in pancreatic cancer progression. We have determined the ability of Quinomycin to inhibit CSCs and the Notch signaling pathway.

Crocetinic acid inhibits hedgehog signaling to inhibit pancreatic cancer stem cells.

Pancreatic cancer is the fourth leading cause of cancer deaths in the US and no significant treatment is currently available. Here, we describe the effect of crocetinic acid, which we purified from commercial saffron compound crocetin using high performance liquid chromatography. Crocetinic acid inhibits proliferation of pancreatic cancer cell lines in a dose- and time-dependent manner.

Histone Demethylases in Colon Cancer.

Cell growth and proliferation are controlled through different posttranslational modifications including demethylation, a process regulated by regulated by the demethylase enzymes. This review focuses on our current understanding of functional and therapeutic potentials of histone demethylases in colon cancer. Colon cancer is the third most common malignancy worldwide and the second leading cause of cancer deaths in the United States.

DNA methyltransferases: a novel target for prevention and therapy.

Cancer is the second leading cause of death in US. Despite the emergence of new, targeted agents, and the use of various therapeutic combinations, none of the available treatment options are curative in patients with advanced cancer. Epigenetic alterations are increasingly recognized as valuable targets for the development of cancer therapies.

Metastasis suppressor KISS1 seems to reverse the Warburg effect by enhancing mitochondrial biogenesis.

Cancer cells tend to utilize aerobic glycolysis even under normoxic conditions, commonly called the "Warburg effect." Aerobic glycolysis often directly correlates with malignancy, but its purpose, if any, in metastasis remains unclear. When wild-type KISS1 metastasis suppressor is expressed, aerobic glycolysis decreases and oxidative phosphorylation predominates.

Bitter melon extracts enhance the activity of chemotherapeutic agents through the modulation of multiple drug resistance.

Recently, we demonstrated that extracts of bitter melon (BME) can be used as a preventive/therapeutic agent in colon cancers. Here, we determined BME effects on anticancer activity and bioavailability of doxorubicin (DOX) in colon cancer cells. BME enhanced the effect of DOX on cell proliferation and sensitized the cells toward DOX upon pretreatment.

3,5-bis(2,4-difluorobenzylidene)-4-piperidone, a novel compound that affects pancreatic cancer growth and angiogenesis.

Dysregulated Notch signaling plays an important role in the progression of cancer. Notch signaling affects tumor growth and angiogenesis through the actions of its ligand Jagged-1. In this study, we developed a novel compound 3,5-bis(2,4-difluorobenzylidene)-4-piperidone (DiFiD) and determined that it inhibits cancer cell growth and its effects on Notch signaling.

Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects.

DNA mismatch repair is required for correcting any mismatches that are created during replication and recombination, and a defective mismatch repair system contributes to DNA damage-induced growth arrest. The colorectal cancer cell line HCT116 is known to have a mutation in the hMLH1 mismatch repair gene resulting in microsatellite instability and defective mismatch repair. Honokiol is a biphenolic compound that has been used in traditional Chinese medicine for treating various ailments including cancer.

Crocetin: an agent derived from saffron for prevention and therapy for cancer.

Cancer is one of the leading causes of death in the United States and accounts for approximately 8 million deaths per year worldwide. Although there is an increasing number of therapeutic options available for patients with cancer, their efficacy is time-limited and non-curative. Approximately 50-60% cancer patients in the United States utilize agents derived from different parts of plants or nutrients (complementary and alternative medicine), exclusively or concurrently with traditional therapeutic regime such as chemotherapy and/or radiation therapy.

Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model.

Crocetin, a carotenoid compound derived from saffron, has long been used as a traditional ancient medicine against different human diseases including cancer. The aim of the series of experiments was to systematically determine whether crocetin significantly affects pancreatic cancer growth both in vitro and/or in vivo. For the in vitro studies, first, MIA-PaCa-2 cells were treated with crocetin and in these sets of experiments, a proliferation assay using H(3)-thymidine incorporation and flow cytometric analysis suggested that crocetin inhibited proliferation.

2-Methoxyestradiol modulates beta-catenin in prostate cancer cells: a possible mediator of 2-methoxyestradiol-induced inhibition of cell growth.

2-Methoxyestradiol (2-ME(2)) is a novel anticancer agent because of its ability to potentiate apoptotic cell death and inhibit cancer cell growth and angiogenesis. The modes of action of this agent, however, have not yet been fully elucidated. In our study, we have investigated whether 2-ME2 is able to modulate beta-catenin signaling in prostate cancer cells, which is one of the major players in cell-cell adhesion, proliferation, apoptosis and carcinogenesis.

Molecular basis of protective effect by crocetin on survival and liver tissue damage following hemorrhagic shock.

Hemorrhagic shock (HS) causes reduction of cellular energy stores, as measured by levels of ATP and ADP. Furthermore, energy depletion may cause mitochondrial damage, which in turn leads to cell death by apoptosis. The hypothesis of the present study is that by enhancing the recovery of cellular ATP and ADP and mitochondrial damage can be reduced, and the extent of apoptosis minimized.

Epidermal growth factor receptor: is a novel therapeutic target for pancreatic cancer?

Expression of epidermal growth factor receptors (EGFR) is exaggerated in pancreatic adenocarcinoma and activation of EGFR appears to have an important role in the growth and differentiation of this and in other tumors. Therefore, blockade or inactivation of EGFR by monoclonal antibodies or by tyrosine kinase inhibitors has significant potential as an effective anti-cancer therapy. One of the very recent significant developments in the field of molecular biology involves the use of antisense of EGFR or EGFR gene silencing in pancreatic cancer cells as a potential targeted therapy for patients with pancreatic adenocarcinoma.

Partial hepatectomy with or without endotoxin does not promote apoptosis in the rat liver.

Background: Liver insufficiency and failure has been described following subtotal hepatectomy. The cause is poorly understood but may be because of attrition of hepatocytes through enhanced cell death pathways such as apoptosis. The trigger for this could be reduction beyond a critical mass of liver tissue or the influence of endotoxin (LPS) on cytokine activation.

Hemorrahagic shock: a new look at an old problem.

Shock research during the past 20 years has resulted in advances in our understanding of the effects of shock and resuscitation at the cellular, molecular, and, increasingly, the genetic level. The authors have measured post-shock restoration of cellular energy stores as an indicator of cellular recovery from shock, and cellular apoptosis as an indicator of tissue damage. Using these assessment tools, we have searched for pharmacologic agents that can be used as adjuncts to fluid and blood resuscitation to reduce cellular damage and--we hope--improve survival.

Glutamine administration during total parenteral nutrition protects liver adenosine nucleotides during and after subsequent hemorrhagic shock.

Background: Glutamine supplementation of total parenteral nutrition (TPN) in stressed patients has been advocated. To determine whether glutamine supplementation affects the host response to conditions of stress, animals were given TPN with or without glutamine for 7 days. They were then subjected to the acute stress of hemorrhagic shock, which results in marked loss of hepatic adenosine triphosphate (ATP) and adenosine diphosphate (ADP), with accumulation of adenosine monophosphate (AMP) and the metabolites adenosine, inosine, hypoxanthine, and xanthine.

Cellular energetics in hemorrhagic shock: restoring adenosine triphosphate to the cells.

Background: This is a review of studies with two agents, glutamine and crocetin, which have been found to enhance recovery of cellular adenosine triphosphate (ATP) and adenosine diphosphate after hemorrhagic shock.

Methods: The studies used a sublethal (30 minutes) reservoir shock model in 300- to 350-g, male, Sprague-Dawley rats, using either ketamine-xylazine or isoflurane anesthesia. Glutamine was given as a 3% (21 mmol/L) solution in Ringer's lactate (630 mg/kg).