Detection of Estrogenic, Antiestrogenic, and Drug Synergistic Activities of Seven Commercially Available Fruits by In Vitro Reporter Assays

Background: Fruits are known to possess antiosteoporotic and anticancer properties in part due to their estrogenic and antiestrogenic activities. Objective: In this study, estrogenic, antiestrogenic, and drug synergistic activities of seven commercially available fruits were evaluated. Materials and Methods: A steroid‑regulated transcription system in Saccharomyces cerevisiae containing a human estrogen receptor alpha expression plasmid, and a β‑galactosidase gene reporter plasmid was employed for the estrogenic, antiestrogenic, and drug agonistic studies. Results: California table grape extract showed the highest estrogenic activity. The estrogenic activities of other extracts ranked as follows: blackberry, red raspberry, strawberry > blueberry > jackfruit, black raspberry. The transcriptional activities of the combination estradiol‑fruit extracts (FEs) (400E equivalents) ranked as follows: blueberry (95.9%), blackberry (86.2%), black raspberry (88.9%), and California table grape (81.5%) > jackfruit (72.2%), and red raspberry (73.2%) > strawberry (60.7%). Black and red raspberry extracts showed the highest synergistic activities with 4‑hydroxytamoxifen (4‑OHT). Black and red raspberry extracts in combination with 4‑OHT lowered the estradiol activity by 74.9% and 73.9%, respectively. The highest synergistic activity with nafoxidine (NAF) was displayed by red raspberry extract. Together, NAF and red raspberry extract lowered estradiol activity by 77.9%. Fold changes were calculated for drug synergistic activities of FEs, and they ranged from 1.3 to 15.3 for 4‑OHT and 1.5–17.4 for NAF, respectively. Conclusions: The active compounds in the FEs studied may be useful in enhancing the antiestrogen activities of chemotherapy drugs and be used as chemopreventive agents for patients at high risk of estrogen‑induced cancers.