Condurango glycoside-rich components stimulate DNA damage-induced cell cycle arrest and ROS-mediated caspase-3 dependent apoptosis through inhibition of cell-proliferation in lung cancer,in vitro and in vivo |
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| Affiliation: | 1. Ataturk University, Science Faculty, Department of Molecular Biology and Genetics, 25240 Erzurum, Turkey;2. Ataturk University, Science Faculty, Department of Chemistry, 25240 Erzurum, Turkey;1. Key Laboratory of Environmental Medicine and Engineering; Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China;2. Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing 210009, China;3. Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009, China;1. IFISE, CONICET-UNR, Rosario, S2002LRL, Argentina;2. IBR, CONICET-UNR, Rosario, S2002LRL, Argentina;3. Facultad de Ciencias Médicas, Universidad Nacional de Rosario (UNR), Rosario, S2002LRL, Argentina;4. Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, S2002LRL, Argentina;1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India;2. Department of Pathology, Rajah Muthiah Medical College, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India;3. Department of Surgery, Rajah Muthiah Medical College, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India |
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| Abstract: | Chemotherapeutic potential of Condurango glycoside-rich components (CGS) was evaluated in NSCLC, in vitro and in BaP-intoxicated rats, in vivo. NSCLC cells were treated with different concentrations of CGS to test their effect on cell viability. Cellular morphology, DNA-damage, AnnexinV-FITC/PI, cell cycle regulation, ROS-accumulation, MMP, and expressions of related signalling genes were critically analysed. 0.22 μg/μl CGS (IC50 dose at 24 h) was selected for the study. CGS-induced apoptosis via DNA damage was evidenced by DNA-ladder formation, increase of AnnexinV-positive cells, cell cycle arrest at subG0/G1 and differential expressions of apoptotic genes. ROS-elevation and MMP-depolarization with significant caspase-3 activation might lead to apoptotic cell death. Anti-proliferative activity was confirmed by EGFR-expression modulation. ROS accumulation and DNA-nick formation with tissue damage-repair activity after post-cancerous CGS treatment, in vivo, supported the in vitro findings. Overall results advocate considerable apoptosis-inducing potential of CGS against NSCLC, validating its use against lung cancer by CAM practitioners. |
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| Keywords: | Condurango glycoside-rich components (CGS) Non small cell lung cancer (NSCLC) H460 Caspase-3 Reactive oxygen species (ROS) Mitochondria membrane potential (MMP) |
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