In Vivo Antitumor Effect of Supercritical CO₂ Extract of Mango Ginger (Curcuma amada Roxb) in U-87MG Human Glioblastoma Nude Mice Xenografts

Abstract

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 CO 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.

Chemical Composition and Biological Activities of Essential Oils of Curcuma Species

“…It was synergistic with irinotecan, a chemotherapy drug. In fact, treatment with a combination of irinotecan and C. amada extract showed almost a complete inhibition of tumor growth [ 227 ]. The extract was highly cytotoxic to human alveolar (SJRH30) and embryonal (RD) rhabdomyosarcoma cell lines, with IC 50 values of 7.13 µg/mL and 7.50 µg/mL, respectively.…”

Mango Ginger Supplementation May Protect Bone Damage Induced by Methotrexate in Rats

“…Several studies have shown that phytochemicals support the stimulation of bone mass by increasing bone development and decreasing bone mineralization despite the unclear mechanisms (6,7,23). MG has numerous biological activities including antioxidant, anticancer, downregulation of the genes related to inflammation, and cell proliferation and stimulation of apoptosis (24,25). Given the negative effects of MTX on bone and the mechanisms it exhibits, we investigated the effects of MG administration on the changes in BMD and some genes that play an important role in bone metabolism in MTXtreated rats.…”

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

“…The traditional use of mango ginger and hops has suggested potential anticancer and other medicinal properties. The supercritical CO 2 extract prepared from the rhizomes of mango ginger (CA) contains 61.7% dialdehyde LDD that is shown to have cytotoxic effects against a variety of human cancer cell lines in vitro and in vivo [18,20,25,26] . Previously, we have shown that CA affect a n array of cellular biochemical pathways in cancer cells inducing the tumor cell death [16][17][18][19] .…”

“…Quantitative analysis by HPLC and GC-MS showed the presence of 61.7% (E)-labda-8 (17),12diene-15,16 dial (LDD), 5.6% beta myrcene, 0.8% beta pinene, 0.3% ocimene, 0.2% beta cariophyllene besides other essential oil components in trace amounts. The chemical fingerprint details of CA have been described in our earlier publication [20]. HL is a dark green, almost black pasty extract with typical hop smell.…”

“…In our earlier investigations, we have reported extensively on the anticancer properties of CA, a proprietary supercritical CO 2 extract of mango ginger ( Curcuma amada Roxb.) both in vitro and in vivo in human glioblastoma cell lines [17][18][19][20]. CA can be combined with conventional cancer drugs like vinbalstine, cyclophosphamide, temozolomide, etoposide and irinotecan with synergistic cytotoxic effects [17][18][19] .…”