Australian ethnomedicinal plant extracts promote apoptosis-mediated cell death in human hepatocellular carcinoma in vitro

Introduction: Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancer with its prevalence continuing to rise. Although the number of cases continues to rise in both developing and developed countries, prognosis remains poor due to a lack of successful treatments. Inspired by the prospect of developing complementary medicines for this condition, we explore several native Australian plants for anti-carcinogenic activity, especially against HCC. Methods: Cytotoxicity assays against HCC cell lines were conducted using various plant extracts. Biochemical profiling of the plant species was conducted for total phenolics and antioxidant capacity, while reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the active apoptotic pathways. Results: Westringia fruticosa and Prostanthera ovalifolia (small-leaved variety) had high antioxidant (410 and 227 mg/g, respectively) and phenolic contents (72.7 and 42.7 mg/g, respectively). P. ovalifolia (small-leaved variety) demonstrated the greatest cytotoxic activity against HepG2 cells (IC50 4.61 ± 0.98 μg/mL) followed by Solanum laciniatum leaves (11.79 ± 0.43 μg/mL) and fruit extracts (ripe, unripe) (14.85 ± 1.80 and 19 ± 1.32 μg/mL, respectively). RT-PCR results confirmed apoptotic events in HepG2 cells, exposed to ripe and unripe S. laciniatum fruit extracts, via caspase-3 pathway. The highest apoptotic induction occurred after 8 hr. Compared to unripe fruits, ripe fruits induced a greater level of apoptosis, as evidenced by a 73 % higher level of caspase-3 mRNA expression and 22 % lower IC50 value. Conclusion: With further investigation, these fruits may provide a valuable source of anticarcinogenic compounds for use as chemotherapeutic or complementary therapies.