Plant derived coumestrol phytochemical targets human skin carcinoma cells by inducing mitochondrial-mediated apoptosis,cell cycle arrest,inhibition of cell migration and invasion and modulation of m-TOR/PI3K/AKT signalling pathway |
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| Authors: | Weiwei Kuang Wenlong Hu Hong Ren Yinhong Shao Bingqian Liu |
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| Affiliation: | 1. Department of Dermatology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, The First People''s Hospital of Lianyungang, Lianyungang 222002, China;2. Department of Ophthalmology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, The First People''s Hospital of Lianyungang, Lianyungang 222002, China |
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| Abstract: | The current study was undertaken to investigate anticancer activity of coumestrol phytoestrogen against human skin cancer. MTT assay was performed for cell viability assessment and clonogenic assay for cell colony formation assessment. Apoptosis was analysed by Annexin V/FITC staining, AO/EB staining and western blotting assays. Effects on the m-TOR/PI3K/AKT signalling pathway were investigated by western blotting. Results indicated that coumestrol induced significant toxicity in human skin cancer cells in contrast to mouse skin cancer cells. The proliferation rate in normal skin cells remained almost intact. Annexin V-FITC and AO/EB staining assays indicated coumestrol induced cytotoxicity in skin cancer cells is mediated through apoptosis stimulation. The apoptosis in skin cancer cells was mediated through caspase-activation. Cell migration and invasion was inhibited by coumestrol in human skin cancer cells via inhibition of MMP-2 and MMP-9 expressions. Moreover, m-TOR/PI3K/AKT signalling pathway in SKEM-5 cells was blocked by coumestrol. |
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| Keywords: | Skin cancer Phytoestrogens Coumestrol Mitochondrial apoptosis Cell cycle |
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