The antineoplastic agent α-bisabolol promotes cell death by inducing pores in mitochondria and lysosomes.
The sesquiterpene α-bisabolol (α-BSB) has been shown to be an effective cytotoxic agent for a variety of human cancer cells in culture and animal models. However, much of its intracellular action remains elusive. We evaluated the cytotoxic action of α-BSB against CML-T1, Jurkat and HeLa cell lines, as preclinical models for myeloid, lymphoid and epithelial neoplasias. The approach included single cell analysis (flow cytometry, immunocytology) combined with cytotoxicity and proliferation assays to characterize organelle damage, autophagy, cytostatic effect, and apoptosis. The study focuses on the relevant steps in the cytotoxic cascade triggered by α-BSB: (1) the lipid rafts through which α-BSB enters the cells, (2) the opening of pores in the mitochondria and lysosomes, (3) the activation of both caspase-dependent and caspase-independent cell death pathways, (4) the induction of autophagy and (5) apoptosis. The effectiveness of α-BSB as an agent against tumor cells is grounded on its capability to act on different layers of cell regulation to elicit different concurrent death signals, thereby neutralizing a variety of aberrant survival mechanisms leading to treatment resistance in neoplastic cell.
Section of Hematology, Cancer Research & Cell Biology Laboratory, Department of Medicine, University of Verona, Verona, Italy.
Antonella
A
Rigo
Section of Hematology, Cancer Research & Cell Biology Laboratory, Department of Medicine, University of Verona, Verona, Italy. fabrizio.vinante@univr.it.
Fabrizio
F
Vinante
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes; C004497:bisabolol; D020169:Caspases
Apoptosis; Autophagy; BCL-2; Lysosomes; Mitochondria; Neoplastic cell lines; α-bisabolol