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Novel harmine derivatives for tumor targeted therapy.

Li S, Wang A, Gu F, Wang Z, Tian C, Qian Z, Tang L, Gu Y - Oncotarget (2015)

Bottom Line: Harmine is a beta-carboline alkaloid found in medicinal plant PeganumHarmala, which has served as a folk anticancer medicine.However, clinical applications of harmine were limited by its low pharmacological effects and noticeable neurotoxicity.Results suggested that the two newharmine derivatives displayed much higher therapeutic effects than non-modified harmine.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Arlington, TX, USA.

ABSTRACT
Harmine is a beta-carboline alkaloid found in medicinal plant PeganumHarmala, which has served as a folk anticancer medicine. However, clinical applications of harmine were limited by its low pharmacological effects and noticeable neurotoxicity. In this study, we modified harmine to increase the therapeutic efficacy and to decrease the systemic toxicity. Specifically, two tumor targeting harmine derivatives 2DG-Har-01 and MET-Har-02 were synthesized by modifying substituent in position-2, -7 and -9 of harmine ring with two different targeting group2-amino-2-deoxy-D-glucose (2DG) and Methionine (Met), respectively. Their therapeutic efficacy and toxicity were investigated both in vitro and in vivo. Results suggested that the two newharmine derivatives displayed much higher therapeutic effects than non-modified harmine. In particular, MET-Har-02 was more potent than 2DG-Har-01 with promising potential for targeted cancer therapy.

No MeSH data available.


Related in: MedlinePlus

A–F.In vitro antitumor efficacy and cytotoxicity of 2DG-Har-01 and MET-Har-02. Tumor cell proliferation rate of HepG-2 cells A. Huh7 cells B. LOVO cells C. SMMC-7721 cells D. MCF-7 cells E. and normal liver cell L02 F. incubated with either 2DG-Har-01, MET-Har-02, harmine or 5-FU. G. and H. Clone formation assay was performed on HepG2 cells. The cells incubated with either harmine (Har) or MET-Har-02 with different concentration (0, 5 10 μM). Data are given as mean ± SD (n = 5). *P < 0.05.
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Figure 2: A–F.In vitro antitumor efficacy and cytotoxicity of 2DG-Har-01 and MET-Har-02. Tumor cell proliferation rate of HepG-2 cells A. Huh7 cells B. LOVO cells C. SMMC-7721 cells D. MCF-7 cells E. and normal liver cell L02 F. incubated with either 2DG-Har-01, MET-Har-02, harmine or 5-FU. G. and H. Clone formation assay was performed on HepG2 cells. The cells incubated with either harmine (Har) or MET-Har-02 with different concentration (0, 5 10 μM). Data are given as mean ± SD (n = 5). *P < 0.05.

Mentions: We investigated the anticancer effects of 2DG-Har-01, MET-Har-02 on five human cancer cell lines (SMMC-7721, HuH7, HepG2, LOVO and MCF-7). The original harmine and common recognized anticancer drug 5-fu were used as control. As shown in Fig. 2A-2E, the modified harmine derivatives, 2DG-Har-01 and MET-Har-02, showed dose-dependent anti-tumor activity in different concentrations. 2DG-Har-01 showed improved antitumor activities than harmine controls on LOVO and SMMC-7721 cells. On the other hand, MET-Har-02 displayed stronger antitumor activity than harmine controls and 5-fu on all cell lines, especially hepatocellular carcinoma cells (SMMC-7721, HuH7).


Novel harmine derivatives for tumor targeted therapy.

Li S, Wang A, Gu F, Wang Z, Tian C, Qian Z, Tang L, Gu Y - Oncotarget (2015)

A–F.In vitro antitumor efficacy and cytotoxicity of 2DG-Har-01 and MET-Har-02. Tumor cell proliferation rate of HepG-2 cells A. Huh7 cells B. LOVO cells C. SMMC-7721 cells D. MCF-7 cells E. and normal liver cell L02 F. incubated with either 2DG-Har-01, MET-Har-02, harmine or 5-FU. G. and H. Clone formation assay was performed on HepG2 cells. The cells incubated with either harmine (Har) or MET-Har-02 with different concentration (0, 5 10 μM). Data are given as mean ± SD (n = 5). *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496197&req=5

Figure 2: A–F.In vitro antitumor efficacy and cytotoxicity of 2DG-Har-01 and MET-Har-02. Tumor cell proliferation rate of HepG-2 cells A. Huh7 cells B. LOVO cells C. SMMC-7721 cells D. MCF-7 cells E. and normal liver cell L02 F. incubated with either 2DG-Har-01, MET-Har-02, harmine or 5-FU. G. and H. Clone formation assay was performed on HepG2 cells. The cells incubated with either harmine (Har) or MET-Har-02 with different concentration (0, 5 10 μM). Data are given as mean ± SD (n = 5). *P < 0.05.
Mentions: We investigated the anticancer effects of 2DG-Har-01, MET-Har-02 on five human cancer cell lines (SMMC-7721, HuH7, HepG2, LOVO and MCF-7). The original harmine and common recognized anticancer drug 5-fu were used as control. As shown in Fig. 2A-2E, the modified harmine derivatives, 2DG-Har-01 and MET-Har-02, showed dose-dependent anti-tumor activity in different concentrations. 2DG-Har-01 showed improved antitumor activities than harmine controls on LOVO and SMMC-7721 cells. On the other hand, MET-Har-02 displayed stronger antitumor activity than harmine controls and 5-fu on all cell lines, especially hepatocellular carcinoma cells (SMMC-7721, HuH7).

Bottom Line: Harmine is a beta-carboline alkaloid found in medicinal plant PeganumHarmala, which has served as a folk anticancer medicine.However, clinical applications of harmine were limited by its low pharmacological effects and noticeable neurotoxicity.Results suggested that the two newharmine derivatives displayed much higher therapeutic effects than non-modified harmine.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Arlington, TX, USA.

ABSTRACT
Harmine is a beta-carboline alkaloid found in medicinal plant PeganumHarmala, which has served as a folk anticancer medicine. However, clinical applications of harmine were limited by its low pharmacological effects and noticeable neurotoxicity. In this study, we modified harmine to increase the therapeutic efficacy and to decrease the systemic toxicity. Specifically, two tumor targeting harmine derivatives 2DG-Har-01 and MET-Har-02 were synthesized by modifying substituent in position-2, -7 and -9 of harmine ring with two different targeting group2-amino-2-deoxy-D-glucose (2DG) and Methionine (Met), respectively. Their therapeutic efficacy and toxicity were investigated both in vitro and in vivo. Results suggested that the two newharmine derivatives displayed much higher therapeutic effects than non-modified harmine. In particular, MET-Har-02 was more potent than 2DG-Har-01 with promising potential for targeted cancer therapy.

No MeSH data available.


Related in: MedlinePlus