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Bio-selective hormonal breast cancer cytotoxic and antioxidant potencies of Melia azedarach L. wild type leaves.

ABSTRACT: Melia azedarach L. is used widely in traditional medicine for local or systemic ailments. Although studies exist on phytochemicals and potencies of Chinese and Indian cultivars of Melia, the present study investigated in vitro antioxidant properties of Melia wild type and its cytotoxicity against T47D cell. The ethanolic extract of the Melia leaves was fractionated with n-hexane, ethyl acetate and water, and the secondary metabolites were obtained. The antioxidant properties were determined with IC50 DPPH (2,2-diphenyl-1-pycrylhydrazyl) radical and FRAP (ferric reducing antioxidant power), while the cytotoxicity was determined with the MTT method. The total phenolic (TPC) and ?-sitosterol (SC) contents were also measured. The results showed that the ethyl acetate fraction had higher antioxidant and cytotoxic activities (IC50 211.89?±?10.86 and 147.90?±?8.49 ?g/mL, respectively) than others. Significant (p?

SUBMITTER: Ervina M

PROVIDER: S-EPMC7044715 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Bio-selective hormonal breast cancer cytotoxic and antioxidant potencies of Melia azedarach L. wild type leaves.

Ervina Martha M Poerwono Hadi H Widyowati Retno R Matsunami Katsuyoshi K Sukardiman

Biotechnology reports (Amsterdam, Netherlands) 20200217

Melia azedarach L. is used widely in traditional medicine for local or systemic ailments. Although studies exist on phytochemicals and potencies of Chinese and Indian cultivars of Melia, the present study investigated in vitro antioxidant properties of Melia wild type and its cytotoxicity against T47D cell. The ethanolic extract of the Melia leaves was fractionated with n-hexane, ethyl acetate and water, and the secondary metabolites were obtained. The antioxid ...[more]

PMID: 32140442

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Project description:BACKGROUND:MAPK/ERK kinases transmit signals from many growth factors/kinase receptors during normal cell growth/differentiation, and their dysregulation is a hallmark of diverse types of cancers. A plethora of drugs were developed to block this kinase pathway for clinical application. With the exception of a recently identified agent, EQW, most of these inhibitors target upstream factors but not ERK1/2; no activator of ERK1/2 is currently available. METHOD:A library of compounds isolated from medicinal plants of China was screened for anti-cancer activities. Three limonoid compounds, termed A1541-43, originally isolated from the plant Melia azedarach, exhibiting strong anti-leukemic activity. The anti-neoplastic activity and the biological target of these compounds were explored using various methods, including western blotting, flow cytometry, molecular docking and animal model for leukemia. RESULTS:Compounds A1541-43, exhibiting potent anti-leukemic activity, was shown to induce ERK1/2 phosphorylation. In contrast, the natural product Cedrelone, which shares structural similarities with A1541-43, functions as a potent inhibitor of ERK1/2. We provided evidence that A1541-43 and Cedrelone specifically target ERK1/2, but not the upstream MAPK/ERK pathway. Computational docking analysis predicts that compounds A1541-43 bind a region in ERK1/2 that is distinct from that to which Cedrelone and EQW bind. Interestingly, both A1541-43, which act as ERK1/2 agonists, and Cedrelone, which inhibit these kinases, exerted strong anti-proliferative activity against multiple leukemic cell lines, and induced robust apoptosis as well as erythroid and megakaryocytic differentiation in erythroleukemic cell lines. These compounds also suppressed tumor progression in a mouse model of erythroleukemia. CONCLUSIONS:This study identifies for the first time activators of ERK1/2 with therapeutic potential for the treatment of cancers driven by dysregulation of the MAPK/ERK pathway and possibly for other disorders.

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Bio-selective hormonal breast cancer cytotoxic and antioxidant potencies of Melia azedarach L. wild type leaves.

Publications

Bio-selective hormonal breast cancer cytotoxic and antioxidant potencies of <i>Melia azedarach</i> L. wild type leaves.

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