Synergistic effect of low-dose cucurbitacin B and low-dose methotrexate for treatment of human osteosarcoma
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Synergistic effect of low-dose cucurbitacin B and low-dose methotrexate for treatment of human osteosarcoma. / Lee, Dhong Hyun; Thoennissen, Nils H; Goff, Catherine; Iwanski, Gabriela B; Forscher, Charles; Doan, Ngan B; Said, Jonathan W; Koeffler, H Phillip.
In: CANCER LETT, Vol. 306, No. 2, 28.07.2011, p. 161-70.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Synergistic effect of low-dose cucurbitacin B and low-dose methotrexate for treatment of human osteosarcoma
AU - Lee, Dhong Hyun
AU - Thoennissen, Nils H
AU - Goff, Catherine
AU - Iwanski, Gabriela B
AU - Forscher, Charles
AU - Doan, Ngan B
AU - Said, Jonathan W
AU - Koeffler, H Phillip
N1 - Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
PY - 2011/7/28
Y1 - 2011/7/28
N2 - We investigated the use of cucurbitacin B, a plant-derived tetracyclic triterpenoid, as a single agent or in combination with methotrexate (MTX) for human osteosarcoma (OS) treatment. Cucurbitacin B showed antiproliferative activity against seven human OS cell lines in vitro accompanying G2/M cell cycle arrest, apoptosis, and inhibition of ERK, Akt, and mTOR proteins. Cucurbitacin B in combination with MTX synergistically inhibited OS cell growth in vitro. Low-dose cucurbitacin B (LD-CuB, 0.5 mg/kg body weight) or low-dose MTX (LD-MTX, 150 mg/kg) failed to decrease the size of human OS xenografts in nude mice. However, combined therapy at identical concentrations inhibited tumor growth by 62% vs. LD-CuB and 81% vs. LD-MTX (p<0.001). Strikingly, the effect persisted even when the dose of MTX was decreased by two thirds (VLD-MTX, 50 mg/kg). In conclusion, cucurbitacin B alone or in combination with MTX shows promising antiproliferative activity against human OS.
AB - We investigated the use of cucurbitacin B, a plant-derived tetracyclic triterpenoid, as a single agent or in combination with methotrexate (MTX) for human osteosarcoma (OS) treatment. Cucurbitacin B showed antiproliferative activity against seven human OS cell lines in vitro accompanying G2/M cell cycle arrest, apoptosis, and inhibition of ERK, Akt, and mTOR proteins. Cucurbitacin B in combination with MTX synergistically inhibited OS cell growth in vitro. Low-dose cucurbitacin B (LD-CuB, 0.5 mg/kg body weight) or low-dose MTX (LD-MTX, 150 mg/kg) failed to decrease the size of human OS xenografts in nude mice. However, combined therapy at identical concentrations inhibited tumor growth by 62% vs. LD-CuB and 81% vs. LD-MTX (p<0.001). Strikingly, the effect persisted even when the dose of MTX was decreased by two thirds (VLD-MTX, 50 mg/kg). In conclusion, cucurbitacin B alone or in combination with MTX shows promising antiproliferative activity against human OS.
KW - Animals
KW - Antimetabolites, Antineoplastic
KW - Apoptosis
KW - Blotting, Western
KW - Bone Neoplasms
KW - Cell Cycle
KW - Cell Proliferation
KW - Dose-Response Relationship, Drug
KW - Drug Synergism
KW - Female
KW - Humans
KW - Immunoenzyme Techniques
KW - Methotrexate
KW - Mice
KW - Mice, Nude
KW - Mitogen-Activated Protein Kinases
KW - Osteosarcoma
KW - Phosphatidylinositol 3-Kinase
KW - Phosphorylation
KW - Proto-Oncogene Proteins c-akt
KW - TOR Serine-Threonine Kinases
KW - Triterpenes
KW - Tumor Cells, Cultured
KW - Xenograft Model Antitumor Assays
U2 - 10.1016/j.canlet.2011.03.001
DO - 10.1016/j.canlet.2011.03.001
M3 - SCORING: Journal article
C2 - 21440986
VL - 306
SP - 161
EP - 170
JO - CANCER LETT
JF - CANCER LETT
SN - 0304-3835
IS - 2
ER -
