scholarly journals Anticancer and Anti-metastatic Effects of Supercritical Extracts of Hops (Humulus lupulus L.) and Mango ginger (Curcuma amada Roxb.) in Human Glioblastoma

2019 ◽  
Vol 10 (4) ◽  
pp. 191
Author(s):  
Cheppail Ramachandran ◽  
Ashley Juan ◽  
Karl-W. Quirin ◽  
Laila Khatib ◽  
Enrique Escalon ◽  
...  

Glioblastoma is one of the most aggressive, lethal and incurable primary brain tumors with a dismal prognosis in humans. Mango ginger (<em>Curcuma amada</em>) and hops <em>(Humulus lupulus</em>) are two botanicals containing phytochemicals with potential anticancer effects. We have investigated the anticancer and antimetastatic properties of supercritical CO<sub>2</sub> extract of mango ginger (CA) and ethanol extract of hops (HL) in the U-87MG human glioblastoma cell line. Both CA and HL individually demonstrate strong cytotoxicity against glioblastoma cells. CompuSyn analysis of cytotoxicity data confirms that CA and HL are synergistic for cytotoxicity with combination index (CI) values of &lt;1.0. Additionally, CA and HL individually as well as the combination significantly inhibit MMP-2 and MMP-9 activity, tumor cell migration (transendothelial cell migration assay) and AKT phosphorylation in U-87MG cells. CA and HL inhibit glycolysis in U-87MG cells as indicated by the inhibition of ATP and lactate synthesis with the CA+HL combination demonstrating strong inhibition of glycolysis via the reduction of ATP and lactate synthesis compared to cells treated by each extract alone. CA and HL treatment down regulates the expression of proteins associated with metastasis, MMP-2 and MMP-9 and up regulates the expression of TIMP1. Proteins associated with apoptosis, inflammation and energy metabolism were also modulated by CA and HL treatment of glioblastoma cells. These results suggest that CA and HL can be combined for the therapeutic management of glioblastomas.

Author(s):  
Cheppail Ramachandran ◽  
Gilda Portalatin ◽  
Karl-W Quirin ◽  
Enrique Escalon ◽  
Ziad Khatib ◽  
...  

Abstract: Mango ginger (: The inhibitory effect of supercritical CO: CA was highly cytotoxic to glioblastoma cell line (IC: These results indicate the molecular targets and mechanisms underlying the anticancer effect of CA in human glioblastoma cells.


2014 ◽  
Vol 20 (2) ◽  
pp. 109-119 ◽  
Author(s):  
Cheppail Ramachandran ◽  
Ivonne V. Lollett ◽  
Enrique Escalon ◽  
Karl-Werner Quirin ◽  
Steven J. Melnick

Mango ginger ( Curcuma amada Roxb.) is among the less-investigated species of Curcuma for anticancer properties. We have investigated the anticancer potential and the mechanism of action of a supercritical CO2 extract of mango ginger (CA) in the U-87MG human glioblastoma cell line. CA demonstrated higher cytotoxicity than temozolomide, etoposide, curcumin, and turmeric force with IC50, IC75, and IC90 values of 4.92 μg/mL, 12.87 μg/mL, and 21.30 μg/mL, respectively. Inhibitory concentration values of CA for normal embryonic mouse hypothalamus cell line (mHypoE-N1) is significantly higher than glioblastoma cell line, indicating the specificity of CA against brain tumor cells. CompuSyn analysis indicates that CA acts synergistically with temozolomide and etoposide for the cytotoxicity with combination index values of <1. CA treatment also induces apoptosis in glioblastoma cells in a dose-dependent manner and downregulates genes associated with apoptosis, cell proliferation, telomerase activity, oncogenesis, and drug resistance in glioblastoma cells.


2021 ◽  
Vol 14 ◽  
Author(s):  
Yiyun Liu ◽  
Yangsheng Chen ◽  
Ruihong Zhu ◽  
Li Xu ◽  
Heidi Qunhui Xie ◽  
...  

Glioblastoma is the most frequent and aggressive primary astrocytoma in adults. The high migration ability of the tumor cells is an important reason for the high recurrence rate and poor prognosis of glioblastoma. Recently, emerging evidence has shown that the migration ability of glioblastoma cells was inhibited upon the activation of aryl hydrocarbon receptor (AhR), suggesting potential anti-tumor effects of AhR agonists. Rutaecarpine is a natural compound with potential tumor therapeutic effects which can possibly bind to AhR. However, its effect on the migration of glioblastoma is unclear. Therefore, we aim to explore the effects of rutaecarpine on the migration of human glioblastoma cells U87 and the involvement of the AhR signaling pathway. The results showed that: (i) compared with other structural related alkaloids, like evodiamine and dehydroevodiamine, rutaecarpine was a more potent AhR activator, and has a stronger inhibitory effect on the glioblastoma cell migration; (ii) rutaecarpine decreased the migration ability of U87 cells in an AhR-dependent manner; (iii) AhR mediated the expression of a tumor suppressor interleukin 24 (IL24) induced by rutaecarpine, and AhR-IL24 axis was involved in the anti-migratory effects of rutaecarpine on the glioblastoma. Besides IL24, other candidates AhR downstream genes both associated with cancer and migration were proposed to participate in the migration regulation of rutaecarpine by RNA-Seq and bioinformatic analysis. These data indicate that rutaecarpine is a naturally-derived AhR agonist that could inhibit the migration of U87 human glioblastoma cells mostly via the AhR-IL24 axis.


2013 ◽  
Vol 15 (8) ◽  
pp. 1048-1057 ◽  
Author(s):  
J. J. Parker ◽  
K. R. Dionne ◽  
R. Massarwa ◽  
M. Klaassen ◽  
N. K. Foreman ◽  
...  

2014 ◽  
Vol 229 (11) ◽  
pp. 1863-1873 ◽  
Author(s):  
Silvia Palumbo ◽  
Paolo Tini ◽  
Marzia Toscano ◽  
Giulia Allavena ◽  
Francesca Angeletti ◽  
...  

2016 ◽  
Vol 22 (2) ◽  
pp. 260-267 ◽  
Author(s):  
Cheppail Ramachandran ◽  
Gilda M. Portalatin ◽  
Adriana M. Prado ◽  
Karl-Werner Quirin ◽  
Enrique Escalon ◽  
...  

Glioblastoma multiforme (GBM) is one the most aggressive and lethal human neoplasms with poor prognosis and very limited positive treatment options. The antitumor effect of supercritical CO2 extract of mango ginger ( Curcuma amada Roxb) (CA) with and without irinotecan (IR) was analyzed in U-87MG human glioblastoma multiforme (GBM) cells in vitro and in nude mice xenografts. CA is highly cytotoxic to GBM cells and is synergistic with IR as indicated by the combination index values of <1 in the CompuSyn analysis. CA inhibits tumor growth rate in GBM xenografts, the inhibition rate being higher than in IR treated group. GBM xenograft mice treated with IR + CA combination showed almost complete inhibition of tumor growth rate. Gene expression analysis of xenograft tumors indicated that IR + CA treatment significantly downregulated anti-apoptotic (Bcl-2 and mutant p53), inflammation-associated (COX-2) and cell division–associated (CCNB2) genes and upregulated pro-apoptotic genes (p21 and caspase-3). These results confirmed the therapeutic efficiency of IR + CA combination against GBM and the need for further clinical investigations.


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