A Phase II Randomized Trial of Lycopene-Rich Tomato Extract Among Men with High-Grade Prostatic Intraepithelial Neoplasia

Abstract

Background A diverse body of evidence suggests that lycopene might inhibit prostate cancer development. We conducted a 6-month repeat biopsy randomized trial among men with HGPIN. Here we report results for serum lycopene, PSA and IGF proteins, histopathological review, and tissue markers for proliferation (MCM-2) and cell cycle inhibition (p27). Methods Participants consumed placebo or tomato extract capsules containing 30 mg/day lycopene. Pre- and post-treatment biopsies were immunostained and digitally scored. Serum lycopene was determined by LC-MS-MS. In secondary analyses, pathologists blindly reviewed each biopsy to score histological features. Results 58 men completed the trial. Serum lycopene increased 0.55 μmol/L with treatment and declined 0.29 μmol/L with placebo. We observed no meaningful differences in PSA, IGF-1 or IGFBP3 concentrations between groups, nor any differences in expression of MCM-2 or p27 in epithelial nuclei. Prevalences of cancer, HGPIN, atrophy or inflammation post-treatment were similar; however, more extensive atrophy and less extensive HGPIN was more common in the lycopene group. Conclusions Despite large differences in serum lycopene following intervention, no treatment effects were apparent on either the serum or benign tissue endpoints. Larger studies are warranted to determine whether changes observed in extent of HGPIN and focal atrophy can be replicated.

Phytotherapeutics in cancer invasion and metastasis

“…Schwenke and coworkers, on the contrary, showed stable PSA levels in hormone refractory prostate cancer patients, and no clinical improvement was reported (15-mg/day lycopene; Schwenke, Ubrig, Thürmann, Eggersmann, & Roth, 2009). These results were confirmed by other studies: 30 mg/day dosage did not modify PSA (Bunker et al, 2007;Gann et al, 2015) and had no effect in androgen-independent prostate cancer patients (Jatoi et al, 2007). Similar results were also obtained by Mariani et al in high-grade prostatic intraepithelial neoplasia patients with 25-mg/day administration (Mariani et al, 2014).…”

ProDiet: A Phase II Randomized Placebo-controlled Trial of Green Tea Catechins and Lycopene in Men at Increased Risk of Prostate Cancer

“…The ProDiet dietary lycopene intervention equates to tomato consumption previously associated with a reduced prostate cancer risk in ProtecT trial participants (36). However, a small placebo-controlled trial of lycopene supplementation in men with HGPIN showed no differences in expression of tissue markers for proliferation or cell-cycle inhibition (MCM-2 and p27, primary endpoints), PSA or cancer rates on rebiopsy at 6 months (37). Lycopene has cardiovascular benefits although not through lowering blood pressure so different endpoints would be needed in a definitive trial to measure its broader impacts (38).…”

MCM7 amplification and overexpression promote cell proliferation, colony formation and migration in esophageal squamous cell carcinoma by activating the AKT1/mTOR signaling pathway

“…Mini-chromosome maintenance protein complex (MCM) is a eukaryotic DNA helicase complex required for initiation of DNA replication. The MCM proteins include six members, MCM2 to MCM7, and are considered as molecular markers of proliferation in several types of cancer (3)(4)(5)(6). MCM7 is a critical component of DNA replication licensing complex, and is overexpressed in multiple human malignancies including hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate carcinoma and esophageal squamous cell carcinoma (7)(8)(9)(10).…”