Prostate cancer is a global issue, as the current leading type of cancer diagnosed in men with high prevalence in the U.S., South America, Central and South Africa, and Australia. Whereas, mortality rates currently are highest in regions with an unstable healthcare systems or lack thereof. Current treatments for advanced stages of prostate cancer often results in recurrence. Flavonoids are natural compounds ubiquitously distributed in fruits, vegetables, and leaves which have shown to have anti-inflammatory, anti-fungal, anti-mutagenic, and anti-carcinogenic properties. A Sub-class flavone, luteolin, has demonstrated to have capability in suppressing prostate cancer cell proliferation in cell models and in reducing tumor size in mice models. However, the therapeutic potential of luteolin is limited by its moderate potency. To alleviate this drawback, fifteen new 7-O-substituted-3',4',5-O-tertramethylluteolins have been designed and synthesized from commercially available hesperidin through a four-step procedure, including oxidation, global methylation, glucoside hydrolysis, O-alkylation, and N-alkylation. Among them, thirteen derivatives have been evaluated for in vitro potency against both androgen receptor-positive LNCaP cells and androgen receptor-null DU145 and PC-3 cell lines. Luteolin and enzalutamide (a current leading prostate cancer therapy) were used as positive controls. The following conclusions can be drawn from our current data from the WST-1 cell proliferation essay: (1) modification on 7-OH of trimethylluteolin can significantly improve its antiproliferative potency; (2) 7-O-bromopropyl-3',4',5-O-tertramethylluteolin was established as the optimal compound that is more effective towards androgen receptor-positive LNCaP cells than androgen receptor-null cell models; and (3) the optimal derivative exhibits greater efficacy than enzalutamide in the LNCaP cell model.

Luteolin derivatives selectively suppress androgen receptor-positive LNCaP prostate cancer cell proliferation

ACS Fall 2020 Virtual Meeting

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