Cytotoxic Synergism between a Proprietary Commiphora mukul Gum Extract GU-MCT810, 2-deoxy-D-glucose, and Metformin in Human Alveolar Rhabdomyosarcoma and Hepatoma Cell Lines In vitro
Cheppail Ramachandran *
Department of Pathology, Nicklaus Children’s Hospital, Miami, FL 33155, USA and Dharma Biomedical LLC, 12777 Cutler Road, Miami, FL 33156, USA.
Karl-Werner Quirin
Flavex Naturextrakte GmbH, Rehlingen, Germany.
Steven J. Melnick
Department of Pathology, Nicklaus Children’s Hospital, Miami, FL 33155, USA and Dharma Biomedical LLC, 12777 Cutler Road, Miami, FL 33156, USA.
*Author to whom correspondence should be addressed.
Abstract
In this investigation we have analyzed the synergism for the cytotoxic effect of a proprietary guggul gum extract (GU), 2-deoxy-D-glucose (2-DG) and metformin (Met) in SJRH30 human alveolar rhabdomyosarcoma and HepG2 hepatoma cell lines in vitro. 2-DG and Met as single agents have weak cytotoxic effects in both cell lines. However, the combination of GU+2-DG, GU+Met and 2-DG+Met showed synergism for cytotoxic effect by CompuSyn analysis. Therefore, GU can be included in the combination of drugs involving 2-DG and Met to have synergistic effect. GU also showed a dose-dependent increase in cellular glucose uptake in HepG2 cells like the antidiabetic drug 2,4-thiozolidine dione (TZ). The demonstration of synergism of anticancer effects between GU, metformin and 2-DG, suggest that their mechanisms are in general complementary, though further studies are required to delineate the mechanism of GU, 2-DG and metformin combinations.
Keywords: Anticancer effect, guggul, 2-deoxy-D-glucose, metformin, rhabdomyosarcoma, hepatoma, cytotoxicity, synergism, glucose uptake