A New Synthetic Curcuminoid Displays Antitumor Activities in Metastasized Melanoma
Authors
Leonard Kaps
Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany; [email protected] (A.K.); [email protected] (H.T.); [email protected] (P.S.)
Adrian Klefenz
Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany; [email protected] (A.K.); [email protected] (H.T.); [email protected] (P.S.)
Henry Traenckner
Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany; [email protected] (A.K.); [email protected] (H.T.); [email protected] (P.S.)
Paul Schneider
Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany; [email protected] (A.K.); [email protected] (H.T.); [email protected] (P.S.)
Ion Andronache
Research Center for Integrated Analysis and Territorial Management, University of Bucharest, 030018 Bucharest, Romania; [email protected]
Bernhard Biersack
Organic Chemistry 1, University Bayreuth, 95447 Bayreuth, Germany; [email protected]
Detlef Schuppan
Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany; [email protected] (A.K.); [email protected] (H.T.); [email protected] (P.S.)
Keywords:
black skin cancer, solid cancer, synthetic derivative of natural product, anticancer drug, curcuma longa, Ayurveda, turmeric, pulmonary metastases
Abstract
Aim: The semisynthetic derivatives MePip-SF5 and isogarcinol, which are aligned with the natural products curcumin and garcinol, were tested for their antitumor effects in a preclinical model of pulmonary melanoma metastasis. Methods and results: MePip-SF5 was almost five times more effective in inhibiting B16F10 melanoma cell proliferation than its original substance of curcumin (IC50 MePip-SF5 2.8 vs. 13.8 µM). Similarly, the melanoma cytotoxicity of isogarcinol was increased by 40% compared to garcinol (IC50 3.1 vs. 2.1 µM). The in vivo toxicity of both drugs was assessed in healthy C57BL/6 mice challenged with escalating doses. Isogarcinol induced toxicity above a dose of 15 mg/kg, while MePip-SF5 showed no in vivo toxicity up to 60 mg/kg. Both drugs were tested in murine pulmonary metastatic melanoma. C57BL/6 mice (n = 10) received 500,000 B16F10 melanoma cells intravenously. After intraperitoneal injection of MePip-SF5 (60 mg/kg) or isorgarcinol (15 mg/kg) at days 8, 11 and 14 and sacrifice at day 16, the MePip-SF5-treated mice showed a significantly (p < 0.05) lower pulmonary macroscopic and microscopic tumor load than the vehicle-treated controls, whereas isogarcinol was ineffective. The pulmonary RNA levels of the mitosis marker Bub1 and the inflammatory markers TNFα and Ccl3 were significantly (p < 0.05) reduced in the MePip-SF5-treated mice. Both drugs were well tolerated, as shown by an organ inspection and normal liver- and kidney-related serum parameters. Conclusions: The novel curcuminoid MePip-SF5 showed a convincing antimetastatic effect and a lack of systemic toxicity in a relevant preclinical model of metastasized melanoma.
Keywords: black skin cancer, solid cancer, synthetic derivative of natural product, anticancer drug, curcuma longa, Ayurveda, turmeric, pulmonary metastases
Author Biography
Detlef Schuppan, Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany; [email protected] (A.K.); [email protected] (H.T.); [email protected] (P.S.)
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Click on "Archives" to access the full archive of scientific preprints. You may use the categories and the search functionality to find select preprints you're interested in.
