Inhibition of AKT signaling by supercritical CO2 extract of mango ginger (Curcuma amada Roxb.) in human glioblastoma cells

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.

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

International Journal of Phytomedicine ◽

10.5138/09750185.2285 ◽

2019 ◽

Vol 10 (4) ◽

pp. 191

Author(s):

Cheppail Ramachandran ◽

Ashley Juan ◽

Karl-W. Quirin ◽

Laila Khatib ◽

Enrique Escalon ◽

...

Keyword(s):

Cell Migration ◽

Ethanol Extract ◽

Humulus Lupulus ◽

Glioblastoma Cells ◽

Human Glioblastoma ◽

Mango Ginger ◽

Migration Assay ◽

Tumor Cell Migration ◽

Curcuma Amada ◽

Dismal Prognosis

Glioblastoma is one of the most aggressive, lethal and incurable primary brain tumors with a dismal prognosis in humans. Mango ginger (Curcuma amada) and hops (Humulus lupulus) are two botanicals containing phytochemicals with potential anticancer effects. We have investigated the anticancer and antimetastatic properties of supercritical CO2 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 <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.

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Anticancer Potential and Mechanism of Action of Mango Ginger (Curcuma amada Roxb.) Supercritical CO2 Extract in Human Glioblastoma Cells

Journal of Evidence-Based Complementary & Alternative Medicine ◽

10.1177/2156587214563731 ◽

2014 ◽

Vol 20 (2) ◽

pp. 109-119 ◽

Cited By ~ 9

Author(s):

Cheppail Ramachandran ◽

Ivonne V. Lollett ◽

Enrique Escalon ◽

Karl-Werner Quirin ◽

Steven J. Melnick

Keyword(s):

Cell Line ◽

Mechanism Of Action ◽

Dependent Manner ◽

Glioblastoma Cell Line ◽

Glioblastoma Cell ◽

Glioblastoma Cells ◽

Embryonic Mouse ◽

Human Glioblastoma ◽

Mango Ginger ◽

Curcuma Amada

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.

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