Apoptosis is one of the most critical forms of defense against cancer, and the induction of apoptosis by dietary polyphenols represents significant potential for cancer preventive activity. The present study examined polyphenols extracted from selected native Australian fruits--Illawarra plum (Podocarpus elatus Endl., Podocarpaceae), Kakadu plum (Terminalia ferdinandiana Exell, Combretaceae), muntries (Kunzea pomifera F. Muell., Myrtaceae), and native currant (Acrotriche depressa R.Br., Epacridaceae)--for antiproliferative activity against a panel of cancer and normal cell lines. Each fruit selectively inhibited the growth of cancer cell lines in a dose-dependent manner. The mechanism of growth inhibition of the human promyelocytic leukaemia cells (HL-60) was determined to be apoptosis by morphological assessment, DNA fragmentation, flow cytometry, and caspase-3 induction. Furthermore, Kakadu plum was found to activate caspase-7, -9, and poly (ADP-ribose) polymerase (PARP), suggesting it acts via the intrinsic apoptosis pathway. The same fruit also caused direct DNA damage in colon adenocarcinoma cells (HT-29) as detected using the cytokinesis-block micronucleus cytome (CBMN Cyt) assay.