Anti-Cancer Effect of Ginsenoside F2against Glioblastoma Multiforme in Xenograft Model in SD Rats

Double-hit lymphoma (DHL) and double-expressor lymphoma (DEL) are aggressive forms of lymphoma that require better treatments to improve patient outcomes. CKD-581 is a new histone deacetylase (HDAC) inhibitor that exhibited a better safety profile in clinical trials compared to other HDAC inhibitors. Here, we demonstrate that CKD-581 inhibited the class I–II HDAC family via histone H3 and tubulin acetylation. CKD-581 treatment also up-regulated the phosphorylation of histone H2AX (γH2AX, DNA double-strand break marker), and reduced levels of MYC and anti-apoptotic proteins such as BCL-2, BCL-6, BCL-XL, and MCL-1 in DH/DE-diffuse large B cell lymphoma (DLBCL) cell lines. Ultimately, CKD-581 also induced apoptosis via poly(ADP ribose) polymerase 1 (PARP1) cleavage. In a DLBCL SCID mouse xenograft model, CKD-581 exhibited anti-cancer effects comparable with those of rituximab (CD20 mAb). Our findings suggest that CKD-581 could be a good candidate for the treatment of DLBCL.

Download Full-text

Spironolactone, a Classic Potassium-Sparing Diuretic, Reduces Survivin Expression and Chemosensitizes Cancer Cells to Non-DNA-Damaging Anticancer Drugs

Cancers ◽

10.3390/cancers11101550 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1550 ◽

Cited By ~ 2

Author(s):

Tomomi Sanomachi ◽

Shuhei Suzuki ◽

Keita Togashi ◽

Asuka Sugai ◽

Shizuka Seino ◽

...

Keyword(s):

Cancer Cells ◽

Kinase Inhibitors ◽

Xenograft Model ◽

Growth Factor Receptor ◽

Survivin Expression ◽

Mouse Xenograft Model ◽

Anti Cancer ◽

Underlying Mechanisms

Spironolactone, a classical diuretic drug, is used to treat tumor-associated complications in cancer patients. Spironolactone was recently reported to exert anti-cancer effects by suppressing DNA damage repair. However, it currently remains unclear whether spironolactone exerts combinational effects with non-DNA-damaging anti-cancer drugs, such as gemcitabine and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Using the cancer cells of lung cancer, pancreatic cancer, and glioblastoma, the combinational effects of spironolactone with gemcitabine and osimertinib, a third-generation EGFR-TKI, were examined in vitro with cell viability assays. To elucidate the underlying mechanisms, we investigated alterations induced in survivin, an anti-apoptotic protein, by spironolactone as well as the chemosensitization effects of the suppression of survivin by YM155, an inhibitor of survivin, and siRNA. We also examined the combinational effects in a mouse xenograft model. The results obtained revealed that spironolactone augmented cell death and the suppression of cell growth by gemcitabine and osimertinib. Spironolactone also reduced the expression of survivin in these cells, and the pharmacological and genetic suppression of survivin sensitized cells to gemcitabine and osimertinib. This combination also significantly suppressed tumor growth without apparent adverse effects in vivo. In conclusion, spironolactone is a safe candidate drug that exerts anti-cancer effects in combination with non-DNA-damaging drugs, such as gemcitabine and osimertinib, most likely through the suppression of survivin.

Download Full-text

Disrupting Androgen Receptor Functionality with Xanthones from the Mangosteen (Garcinia mangostana) Fruit

Proceedings ◽

10.3390/proceedings2019040050 ◽

2020 ◽

Vol 40 (1) ◽

pp. 50

Author(s):

Jeremy J. Johnson

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Cells ◽

Cellular Proliferation ◽

Xenograft Model ◽

Pharmacokinetic Studies ◽

Garcinia Mangostana ◽

Optimal Dosing ◽

Anti Cancer

The Southeast Asian mangosteen (Garcinia mangostana) contains a class of phytochemicals known as xanthones that possess extensive biological activity. Applications of xanthones, including the most prominent, alpha-mangostin, have been shown to possess anti-cancer, anti-oxidant, and anti-proliferation properties. To confirm the anti-cancer activity of xanthones we have evaluated 9 xanthones for decreasing cellular proliferation of cancer cells. These xanthones include alpha-mangostin, gartanin, 9-hydroxycalabaxanthone, garcinone C, garcinone D, and others. Using this approach, we have focused on understanding the ability of xanthones to disrupt androgen receptor in prostate cancer cells with a combination of cell free and cell-based assays. In addition, we have performed pharmacokinetic studies in mice with alpha-mangostin to characterize the optimal dosing strategy. Taken together, we have identified individual xanthones as capable of disrupting kinases, including CDK4, using cell free biochemical models and cell-based animal models. These results have been further validated in an in vivo xenograft model. Taken together, we have begun to describe the anti-cancer potential of xanthones for prostate cancer.

Download Full-text

Two-stage nanoparticle delivery of piperlongumine and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) anti-cancer therapy

TECHNOLOGY ◽

10.1142/s2339547816500011 ◽

2016 ◽

Vol 04 (01) ◽

pp. 60-69 ◽

Cited By ~ 7

Author(s):

Charles C. Sharkey ◽

Jiahe Li ◽

Sweta Roy ◽

Qianhui Wu ◽

Michael R. King

Keyword(s):

Cancer Cells ◽

Survival Rates ◽

Xenograft Model ◽

Plga Nanoparticles ◽

Mouse Xenograft Model ◽

Anti Cancer ◽

In Vivo Testing ◽

Hct116 Cells

This study outlines a drug delivery mechanism that utilizes two independent vehicles, allowing for delivery of chemically and physically distinct agents. The mechanism was utilized to deliver a new anti-cancer combination therapy consisting of piperlongumine (PL) and TRAIL to treat PC3 prostate cancer and HCT116 colon cancer cells. PL, a small-molecule hydrophobic drug, was encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles. TRAIL was chemically conjugated to the surface of liposomes. PL was first administered to sensitize cancer cells to the effects of TRAIL. PC3 and HCT116 cells had lower survival rates in vitro after receiving the dual nanoparticle therapy compared to each agent individually. In vivo testing involved a subcutaneous mouse xenograft model using NOD-SCID gamma mice and HCT116 cells. Two treatment cycles were administered over 48 hours. Higher apoptotic rates were observed for HCT116 tumor cells that received the dual nanoparticle therapy compared to individual stages of the nanoparticle therapy alone.

Download Full-text

Enhanced anti-cancer activity of microglia by AAV2-mediated IL-12 in the therapy of glioblastoma multiforme

Nature Precedings ◽

10.1038/npre.2009.3101.1 ◽

2009 ◽

Author(s):

Tsung-Lang Chiu ◽

Mei-Jen Wang ◽

Chin-Cheng Su

Keyword(s):

Glioblastoma Multiforme ◽

Anti Cancer ◽

Cancer Activity

Download Full-text

HGG-31. EVALUATE THE ANTI-CANCER OF NOVEL CHELATOR DPC ON GLIOBLASTOMA MULTIFORME CELLS

Neuro-Oncology ◽

10.1093/neuonc/noy059.303 ◽

2018 ◽

Vol 20 (suppl_2) ◽

pp. i95-i95

Author(s):

Godfrey Chi-Fung Chan

Keyword(s):

Glioblastoma Multiforme ◽

Anti Cancer

Download Full-text

CLL-1, a Receptor Expressed on Myeloid Leukemic Stem Cells, Is a Potential Target for Immunotherapy of AML

Blood ◽

10.1182/blood.v112.11.4003.4003 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4003-4003

Author(s):

Wouter Korver ◽

Xiaoxian Zhao ◽

Shweta Singh ◽

Cecile Pardoux ◽

Jingsong Zhao ◽

...

Keyword(s):

Stem Cells ◽

Cytotoxic Activity ◽

Cell Lines ◽

Ex Vivo ◽

Specific Interaction ◽

Myeloid Cells ◽

Xenograft Model ◽

Leukemic Stem Cells ◽

Anti Cancer

Abstract CLL-1 (C-type Lectin-Like Molecule-1) is an inhibitory receptor expressed on myeloid cells which was previously shown to be expressed on AML cancer stem cells. To further validate the potential therapeutic against CLL-1, we generated a series of monoclonal antibodies (mAbs) against CLL-1 and assessed their cytotoxic and anti-cancer activities. While expression of CLL-1 was restricted to myeloid cells, it was expressed in 80% (37/46) of AML blasts but not in ALL blasts (n=5). Expression on AML CD34+/CD38- stem cells was detected in 71% (12/17) of cases. Selected anti-CLL-1 mAbs mediated dose-dependent. Complement Dependent Cytotoxicity (CDC) against various AML-derived cell lines with no detectable cytotoxic activity against lymphoid derived cell lines. Moreover, human embryonic kidney 293 cells became susceptible to anti-CLL-1 mAb mediated killing only after transfection with CLL-1, demonstrating that cytotoxic activity is mediated through a specific interaction with CLL-1. Furthermore, anti-CLL-1 mAbs showed CDC activity against all AML blasts tested in ex vivo assays (n=13), while no activity was observed against ALL blasts. CLL-1 efficiently internalizes upon antibody binding in both 293 transfected cells as well as AML cell lines, demonstrating the potential therapeutic opportunity for toxin-conjugation of anti-CLL-1 mAbs. In vivo anti-cancer activity of the lead chimeric mAb against CLL-1 was tested in an HL-60 xenograft model. In this model, growth of established tumors was reduced by 38% at 5 mg/kg twice weekly dosing. Our results demonstrate CLL-1 as an attractive target for AML with restricted expression on cells from myeloid origin, AML blasts and leukemic stem cells, as well as specific cytotoxic activity in in vitro, ex vivo and in vivo assays. We are currently undertaking additional xenograft models to evaluate the therapeutic potential of these mAbs against primary AML engrafted cells and in combination with chemotherapy in vivo.

Download Full-text