Antioxidative and anti-proliferative potential of Curculigo orchioides Gaertn in oxidative stress induced cytotoxicity: In vitro, ex vivo and in silico studies

• Published in: Food and chemical toxicology Vol. 115; pp. 244 - 259
• Main Authors: Hejazi, Iram Iqbal, Khanam, Rashmin, Mehdi, Syed Hassan, Bhat, Abdul Roouf, Rizvi, M.Moshahid Alam, Thakur, Sonu Chand, Athar, Fareeda
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2018
• Subjects: Anticancer; Antineoplastic Agents, Phytogenic - pharmacology; Antioxidant; Antioxidants - pharmacology; Cell Proliferation - drug effects; Cell Survival - drug effects; Computer Simulation; Curculigo - chemistry; Curculigo orchioides Gaertn; Gas Chromatography-Mass Spectrometry; HeLa; HeLa Cells; Hep G2 Cells; HepG2; Humans; Hydrogen Peroxide - metabolism; Lipid Peroxidation - drug effects; MCF-7 Cells; Molecular docking; Nitric Oxide - metabolism; Oxidative Stress - drug effects; Plant Extracts - pharmacology; AB; L-AA; Curculigo orchioides Gaertn; DPPH; SOD; GST; DAPI; GR; Antioxidant; MTT; Molecular docking; GPx; HeLa; GC-MS; CAT; HepG2; Anticancer; EA; AEA
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2018.03.013

Plant phytoconstituents have been a valuable source of clinically important anticancer agents. Antioxidant and anticancerous activity of plant Curculigo orchioides Gaertn were explored In vitro antioxidant activity, antioxidant enzyme activity of oxidatively stressed tissue, and cell culture studies on human cancer cell lines HepG2, HeLa and MCF-7 were carried out. Active plant fractions were subjected to GC-MS analysis and compounds selected on the basis of their abundance were screened in silico with the help of Auto Dock 4.2 tools with pre-selected antioxidant enzymes. Curculigo orchioides Gaertn plant fractions exhibited significant antioxidant activities by virtue of scavenging of free radicals having IC50 value of ethylacetate fraction (EA) for DPPH radical scavenging assay to be 52.93 ± 0.66 μg/ml. Further, antioxidant enzyme defense of mammalian tissue when treated with plant fractions revealed that enzyme concentrations were refurbished which were increased during oxidative stress. MTT assay on cell lines HepG2, HeLa and MCF-7 presented IC50 values of ethylacetate (EA) fraction as 171.23 ± 2.1 μg/ml, 144.80 ± 1.08 μg/ml and 153.51 μg/ml and aqueous ethylacetate (AEA) fraction as 133.44 ± 1.1 μg/ml, 136.50 ± 0.8 μg/ml and 145.09 μg/ml respectively. Further EA and AEA plant fractions down regulated the levels of antiapoptotic Bcl-2 expression and upregulated the expression of apoptotic proteins caspase-3 and caspase-8 through an intrinsic ROS-mediated mitochondrial dysfunction pathway. Key findings explained that fractions of Curculigo orchioides Gaertn inhibited oxidative stress by increasing the antioxidant enzyme content and have anticancerous potential on cancer cell lines HepG2, HeLa and MCF-7. [Display omitted] •C.orchioides Gaertn exhibited significant antioxidant activities.•EA and AEA extracts are enhancers of antioxidant and anticancer enzymes.•EA and AEA extracts upregulate Caspase-3/8 and downregulate Bcl-2.