title: Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells.
abstract: Isostrychnopentamine (ISP) is an indolomonoter-penic alkaloid that is present in the leaves of Strychnos usambarensis, an East African small tree. We have reported previously pro-apoptotic effects induced in vitro by ISP in the human HCT-116 colon cancer cell line, a model that displays relative sensitivity to apoptosis. In the present study, we observed that the in vitro growth inhibitory activities of ISP are similar in cancer cells that display sensitivity versus resistance to apoptosis. We made use of the U373 glioblastoma and the A549 non-small cell lung cancer (NSCLC) cell lines as models relatively resistant to apoptosis, and the human PC-3 prostate cancer cell line as a model relatively sensitive to apoptosis. While ISP induced transient decreases in [ATP]i and apoptosis in human U373 GBM cells, it did not provoke such features in A549 NSCLC cells. It thus seems that ISP-induced anti-cancer activity can lead to pro-apoptotic effects as a consequence, while apoptosis seems not to be the main cause by which ISP induces cancer cell death. ISP is a compound that merits further investigations in order to: i) identify the mechanism(s) of action by which it kills cancer cells, and ii) hemisynthesize novel ISP derivatives aiming to overcome, at least partly, the resistance of metastatic cancers to apoptosis.
authors.affiliation: Laboratoire de Toxicologie, Département de BioAnalyse et Toxicologie Pharmaceutique, Institut de Pharmacie, Université Libre de Bruxelles, 1050 Brussels, Belgium.
authors.forename: El-Hadj
authors.initials: el-H
authors.lastname: Saidou Balde
authors.forename: Véronique
authors.initials: V
authors.lastname: Mégalizzi
authors.forename: Martine
authors.initials: M
authors.lastname: Cao
authors.forename: Luc
authors.initials: L
authors.lastname: Angenot
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Marc
authors.initials: M
authors.lastname: Van Damme
authors.forename: Michel
authors.initials: M
authors.lastname: Frederich
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D002243:Carbolines / Q000302:isolation & purification / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D018515:Plant Leaves; D011471:Prostatic Neoplasms / Q000473:pathology; D031451:Strychnos / Q000737:chemistry; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002243:Carbolines; C473210:isostrychnopentamine; D000255:Adenosine Triphosphate