title: Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis.
abstract: Despite remarkable progress in the discovery and development of novel cancer therapeutics, cancer remains the second leading cause of death in the world. For many years, compounds derived from plants have been at the forefront as an important source of anticancer therapies and have played a vital role in the prevention and treatment of cancer because of their availability, and relatively low toxicity when compared with chemotherapy. More than 3000 plant species have been reported to treat cancer and about thirty plant-derived compounds have been isolated so far and have been tested in cancer clinical trials. The mechanisms of action of plant-derived anticancer drugs are numerous and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and caspase and/or p53-dependent or independent mechanisms. Alternative modes of cell death by plant-derived anticancer drugs are emerging and include mainly autophagy, necrosis-like programmed cell death, mitotic catastrophe, and senescence leading to cell death. Considering that the non-apoptotic cell death mechanisms of plant-derived anticancer drugs are less reviewed than the apoptotic ones, this paper attempts to focus on such alternative cell death pathways for some representative anticancer plant natural compounds in clinical development. In particular, emphasis will be on some promising polyphenolics such as resveratrol, curcumin, and genistein; alkaloids namely berberine, noscapine, and colchicine; terpenoids such as parthenolide, triptolide, and betulinic acid; and the organosulfur compound sulforaphane. The understanding of non-apoptotic cell death mechanisms induced by these drugs would provide insights into the possibility of exploiting novel molecular pathways and targets of plant-derived compounds for future cancer therapeutics.
authors.affiliation: Department of Biology, American University of Beirut, Beirut, Lebanon.|Nature Conservation Center, American University of Beirut, Beirut, Lebanon.
authors.forename: Hala
authors.initials: H
authors.lastname: Gali-Muhtasib
authors.affiliation: Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.
authors.forename: Raed
authors.initials: R
authors.lastname: Hmadi
authors.affiliation: Department of Biology, American University of Beirut, Beirut, Lebanon.
authors.forename: Mike
authors.initials: M
authors.lastname: Kareh
authors.affiliation: Department of Biology, American University of Beirut, Beirut, Lebanon.|Nature Conservation Center, American University of Beirut, Beirut, Lebanon.
authors.forename: Rita
authors.initials: R
authors.lastname: Tohme
authors.affiliation: Nature Conservation Center, American University of Beirut, Beirut, Lebanon. nd03@aub.edu.lb.|Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon. nd03@aub.edu.lb.
authors.forename: Nadine
authors.initials: N
authors.lastname: Darwiche
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016159:Tumor Suppressor Protein p53; D020169:Caspases
keywords: Anticancer drugs; Apoptosis; Autophagy; Cell death; Medicinal plants; Necrosis; Senescence