Lycopene enhances the anti-proliferative and pro-apoptotic effects of capsaicin in prostate cancer in vitro

Abstract

Background: Increasing evidence suggests dietary factors influence the development and progression of prostate cancer (PCa). The chemopreventive properties of lycopene, the antioxidant found in tomatoes, have been extensively studied for PCa; however, the effect of lycopene, as a single agent, remains unclear. Studies that are more promising, involve using lycopene in combination with other dietary agents. Capsaicin, the active compound in chilli peppers, is reported to exert potent anti-cancer effects in both in vitro and in vivo PCa models. We have investigated whether lycopene enhances the anti-proliferative and apoptotic effects of capsaicin in vitro. Methods: Using the MTS Cell Proliferation Assay we assessed the anti-proliferative effect of capsaicin alone, or in combination with lycopene in human PCa cell lines (LNCaP, PC3, PC3-AR2, DU145) and prostate stromal cells. Flow cytometry and Western Blotting techniques were used to assess potential mechanisms of interaction. Results: Capsaicin exhibited anti-proliferative and pro-apoptotic effects, which were significantly enhanced with the addition of lycopene to PCa cells. The greatest effects were observed in androgen-sensitive cell lines. Detailed mechanistic studies revealed this combination may be interrupting the androgen-signaling pathways; independent of TRP-V1 signaling. Cell cycle analysis revealed that capsaicin and lycopene induce a cell cycle arrest, corresponding to alterations in tumor-suppressor proteins. Treating LNCaP cells with capsaicin and lycopene also altered proteins involved the apoptosis signaling pathway including, cleaved PARP, Caspase-3 and Bax/Bcl-xL expression. Conclusions: Our results suggest that lycopene enhances the anti-cancer properties of capsaicin. Understanding micronutrient interactions may help improve current chemoprevention strategies.

Capsaicin reduces the metastatic burden in the transgenic adenocarcinoma of the mouse prostate model

“…Unfortunately, these concentrations are still 10‐100‐fold higher than our in vitro analysis that has been reported. However, it is still unclear whether capsaicin can accumulate in certain tissues (i.e., prostate tissue), as reported with other dietary agents (e.g., lycopene) . It is also possible that the metabolite glucuronide that we identified may possess anti‐cancer properties.…”

“…The apoptotic effect of capsaicin on cancer cells has been more consistently documented in the recent literature across various cancer sites, including the prostate . The majority of these studies have reported that capsaicin acts predominately by inducing intrinsic apoptosis through the generation of reactive oxygen species (ROS), disruption of the mitochondrial membrane, alterations in bax to bcl‐2 ratio and subsequent release of cytochrome C, and by the activation of the caspase–cascade .…”

Endogenous TRPV1 stimulation leads to the activation of the inositol phospholipid pathway necessary for sustained Ca2+ oscillations

“…Although the abovementioned physiological processes are associated with increased cell viability and mitogenic processes, there are only few studies reporting that CAPS increase cell proliferation of cancer cells. While CAPS (50 μM) increases the proportion of cells present in the G 2 phase, the proportion of G 0 /G 1 cells is decreased compared to control (untreated) LNCaP cells [52]. Similarly Malagarie-Cazenave et al…”

Cannabinoid WIN 55,212‐2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid‐receptor 2 dependent manner

“…Western Blot analyses of lysates from PC3 treated cells were carried out as described. 10 Briefly, PC3 cells were plated at a density of 1 × 10 6 cells per 10 cm plate. Twenty-four hours after plating, adherent cells were treated with WIN (10-20 μM).…”