title: Ipobscurine, an indole alkaloid from Ipomoea obscura, inhibits tumor cell invasion and experimental metastasis by inducing apoptosis.
abstract: In the present study, we demonstrate that ipobscurine, an indole alkaloid fraction isolated from Ipomoea obscura, can reduce the formation of B16F-10 melanoma-induced metastatic nodules and inhibit the proliferation, migration, and invasion of B16F-10 melanoma cells in vitro, possibly by inhibiting pro-metastatic genes such as matrix metalloproteinases (MMPs) and inflammatory mediators such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines. Ipobscurine may also promote apoptosis by up-regulating pro-apoptotic molecules such as caspase-3, p53, and Bax and by down-regulating anti-apoptotic Bcl-2. In addition, we have observed that ipobscurine suppresses various transcription factors such as nuclear factor-κB (NF-κB) and activator protein, which are possibly associated with the suppression of apoptosis in cancer cells. Ipobscurine has also been shown to inhibit cell growth with arrest at G1 and reduce transition to the S and G2/M phases of the cell cycle.
authors.affiliation: Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.
authors.forename: T
authors.initials: T
authors.lastname: Hamsa
authors.forename: Girija
authors.initials: G
authors.lastname: Kuttan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D027741:Ipomoea / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D026121:Indole Alkaloids; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; C568076:ipobscurine; D019716:Tissue Inhibitor of Metalloproteinase-2; D051546:Cyclooxygenase 2; D020782:Matrix Metalloproteinases