title: In vitro antimetastatic activity of koetjapic acid against breast cancer cells.
abstract: Breast cancer is the most common cancer in women, and it can metastasize very rapidly. Tumor metastasis is the primary cause of cancer deaths. In the present study, we investigated the capability of koetjapic acid, a natural triterpene, in the induction of apoptosis and the inhibition of metastasis in the breast cancer cell line (MCF 7). The effects of koetjapic acid against 4 steps of metastasis have been assessed, including cell survival, clonogenicity, migration and invasion. Koetjapic acid exhibited cytotoxic activity against MCF 7 cells with an IC(50) of 68.88±6.075 μg/mL. The mechanism of cell death was confirmed due to the induction of apoptosis machineries; early and late apoptosis-related changes were detected, including the stimulation of caspase 3/7 activities, apoptosis-related morphological changes such as membrane blebbing, chromatin condensation and DNA fragmentation. A mitochondrial apoptosis pathway was found to be involved in koetjapic acid-induced cell death induction. Moreover, at a sub-toxic dose (15 μg/mL), Koetjapic acid inhibited cell migration and invasion significantly. Finally, koetjapic acid inhibited the colony formation properties of MCF 7 significantly. These results indicate that koetjapic acid possesses significant antitumor and antimetastatic effects, and warrants further investigation.
authors.affiliation: EMAN Testing & Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: Zeyad D
authors.initials: ZD
authors.lastname: Nassar
authors.forename: Abdalrahim F A
authors.initials: AF
authors.lastname: Aisha
authors.forename: Fouad Saleih R
authors.initials: FS
authors.lastname: Al Suede
authors.forename: Aman Shah
authors.initials: AS
authors.lastname: Abdul Majid
authors.forename: Amin Malik Shah
authors.initials: AM
authors.lastname: Abdul Majid
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009361:Neoplasm Invasiveness; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; C573794:koetjapic acid; D053148:Caspase 3; D053179:Caspase 7