title: Marine steroid derived from Acropora formosa enhances mitochondrial-mediated apoptosis in non-small cell lung cancer cells.
abstract: p53 pathway has been revealed to mediate cellular stress responses and trigger DNA repair, cell cycle arrest, senescence, and apoptosis. We isolated 2-ethoxycarbonyl-2-β-hydroxy-A-nor-cholest-5-ene-4one (ECHC) from butanol extracts of scleractinian coral Acropora formosa and reported its potential antioxidant and antimicrobial activity as well as less toxicity against zebrafish Danio rerio. In the present study, we intend to explore p53-mediated apoptosis pathway enhanced by ECHC in A549 human non-small cell lung cancer cell lines. This report shows that ECHC increases ROS generation and sensitizes mitochondrial membrane that leads to the release of cytochrome C (Cyto C) into cytosol. Further, ECHC decreases the expression of antiapoptotic genes such as TNF-α, IL-8, Bcl2, MMP2, and MMP9 which are actively involved in cancer cell proliferation, invasion, and metastasis etc. It also increases the expression of apoptotic genes Cyto C, Bax, and p21, which are responsible for cell cycle arrest and cell death. The tumor suppressor p53 was also observed to be upregulated during ECHC treatment in untransformed cells and was more likely to result in cell cycle arrest, senescence, and apoptosis. Finally, ECHC also down regulates the expression of caspase-9 and caspase-3 which are the death stage of intrinsic apoptosis. Our findings suggested that ECHC enhances ROS generation and mitochondrial sensitization determines the threshold for irreversible p53-mediated intrinsic apoptosis pathway.
authors: DNA Barcoding and Marine Genomics Lab, Department of Marine Science, Bharathidasan University, Tiruchirappalli, 620024, Tamil Nadu, India.
authors: Ramalingam
authors: R
authors: Vaikundamoorthy
authors: Department of Genetics, Institute of Basic Medical Sciences, Madras University, Taramani Campus, Chennai, 600113, Tamil Nadu, India.
authors: Revathidevi
authors: R
authors: Sundaramoorthy
authors: Cancer Biology Lab, Department of Biochemistry, Bharathidasan University, Tiruchirappalli, 620024, Tamil Nadu, India.
authors: Varunkumar
authors: V
authors: Krishnamoorthy
authors: Cancer Biology Lab, Department of Biochemistry, Bharathidasan University, Tiruchirappalli, 620024, Tamil Nadu, India.
authors: Ravikumar
authors: R
authors: Vilwanathan
authors: DNA Barcoding and Marine Genomics Lab, Department of Marine Science, Bharathidasan University, Tiruchirappalli, 620024, Tamil Nadu, India. drrajaram69@rediffmail.com.
authors: Rajaram
authors: R
authors: Rajendran
mesh_terms: D000072283:A549 Cells; D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002783:Cholestenones; D020869:Gene Expression Profiling; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: C000614199:2-ethoxycarbonyl-2-beta-hydroxy-A-nor-cholest-5-ene-4-one; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002783:Cholestenones; D016209:Interleukin-8; D016328:NF-kappa B; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53
keywords: A549 cells; Acropora formosa; Apoptosis; Caspase; ECHC; p53