Title:Isolation, Purification and Characterization of a Novel Steroidal Saponin Cholestanol Glucoside from Lasiodiplodia theobromae that Induces Apoptosis in A549 Cells
Volume: 16
Issue: 7
Author(s): Jinu Mathew Valayil, Gini C. Kuriakose and C. Jayabaskaran
Affiliation:
Keywords:
Apoptosis, cholestanol glucoside, cytotoxicity, endophytic fungi, Lasiodiplodia theobromae, reactive oxygen species.
Abstract: Search for novel anticancer lead molecules continues to be a major focus of cancer research due to the
limitations of existing drugs such as lack of tumor selectivity, narrow therapeutic index and multidrug resistance
of cancer types. Natural molecules often possess better pharmacokinetic traits compared to synthetic molecules as
they continually evolve by natural selection process to interact with biological macromolecules. Microbial
metabolites constitute nearly half of the pharmaceuticals in market today. Endophytic fungi, owing to its rich
chemical diversity, are viewed as attractive sources of novel bioactive compounds. In the present study, we report
the purification and characterization of a novel steroidal saponin, cholestanol glucoside (CG) from Saraca asoca
endophytic fungus Lasiodiplodia theobromae. The compound was assessed for its cytotoxic potentialities in six
human cancer cell lines, A549, PC3, HepG2, U251, MCF7 and OVCAR3. CG exhibited significant cytotoxicities
towards A549, PC3 and HepG2 among which A549 cells were most vulnerable to CG treatment. However, CG
treatment exhibited negligible cytotoxicity in non malignant human lung fibroblast cell line (WI-38). Induction of cell death by CG
treatment in A549 cells was further investigated. CG induced the generation of reactive oxygen species (ROS) and mitochondrial membrane
permeability loss followed by apoptotic cell death. Mitochondrial membrane depolarization and apoptotic cell death in CG treated A549
cells were completely blocked in presence of an antioxidant, N-acetyl cysteine (NAC). Hence it could be concluded that CG initiates
apoptosis in cancer cells by augmenting the basal oxidative stress and that the generation of intracellular ROS is crucial for the induction
of apoptosis.
