Procyanidin‐B2 enriched fraction of cinnamon acts as a proteasome inhibitor and anti‐proliferative agent in human prostate cancer cells

Abstract

Altered activity of the proteolytic machine-the 26S proteasome is observed in many disease conditions. Hence, either inhibition or activation of the 26S proteasome is thought to be a novel therapy for treatment of certain diseases such as cancer and neurodegenerative disorders. In this study, we tested the potential of cinnamon and one of its active ingredients, procyanidin-B2 (PCB2), in inhibiting the catalytic activities of the proteasome and suppressing prostate cancer cell growth. Proteasome activities were measured using fluorogenic substrates specific for the different enzymatic activities of the 26S proteasome by flourometry. Cell viability was assessed using the 3-[4, 5-dimethylthiazol-2-yl]-2.5-diphenyl-tetrazolium bromide assay, while apoptosis was examined by Hoechst and propidium iodide staining and caspase-3 activity. Both, the cinnamon extract and its PCB2-enriched F2 fraction inhibited the catalytic activities of the purified proteasome and the proteasome in cancer cells but not in normal cells. Furthermore, cinnamon and its active component decreased cell proliferation of human prostate cancer cells but not normal lung cells, decreased expression of anti-apoptotic and angiogenic markers in prostate cancer cell lysates. These results demonstrate that cinnamon extract and its PCB2-enriched fraction act as proteasome inhibitors and have prospects as anti-cancer agents. © 2018 IUBMB Life, 70(5):445-457, 2018.

Procyanidin B2 inhibits lipopolysaccharide‑induced apoptosis by suppressing the Bcl‑2/Bax and NF‑κB signalling pathways in human umbilical vein endothelial cells

“…Procyanidin B2 (epicatechin-(4β-8)-epicatechin; PB2), a phenolic compound, primarily exists in common fruits, including red grapes, cocoa, lindera aggregate and cinnamon (22). PB2 isolated from cinnamon can significantly decline cell viability and accelerate apoptosis in prostate cancer cells, and the proapoptotic effect of PB2 might be associated with caspase-3 activity (23). PB2 is a bioactive component and a potent antioxidant for restoring and maintaining homeostasis (24).…”

Natural products as home‐based prophylactic and symptom management agents in the setting of COVID‐19

“…Studies have shown the role of trypsin and cathepsin L in cleavage and activation of spike protein and its binding to ACE2, during the SARS‐CoV infection (Belouzard, Chu, & Whittaker, 2009; Simmons et al, 2011). In this context, cinnamon as a trypsin inhibitor (Gopalakrishnan, Ediga, Reddy, Reddy, & Ismail, 2018; Shahwar, Raza, Shafiq‐Ur‐Rehman, Abbasi, & Atta‐Ur‐Rahman, 2012) could have a therapeutic role against the SARC‐CoV‐2 infection in COVID‐19.…”

“…Studies have shown the role of trypsin and cathepsin L in cleavage and activation of spike protein and its binding to ACE2, during the SARS-CoV infection(Belouzard, Chu, & Whittaker, 2009;Simmons et al, 2011). In this context, cinnamon as a trypsin inhibitor(Gopalakrishnan, Ediga, Reddy, Reddy, & Ismail, 2018;Shahwar, Raza, Shafiq-Ur-Rehman, Abbasi, & Atta-Ur- Rahman, 2012) could have a therapeutic role against the SARC-CoV-2 infection in COVID-19.In CCL 4 and LPS-stimulated rat and mice, cinnamon extracts reduced MDA and increased levels of antioxidant markers catalase and SOD. It also reduced antiinflammatory markers TNF-α/IL-6, reduced phosphorylation of MAPKs (JNK, p38 and ERK1/2), and interfered with NF-κB activation by inhibiting the degradation of IκBα.…”

Curry versus cancer: Potential of some selected culinary spices against cancer with in vitro, in vivo, and human trials evidences

“…Cinnamon extract inhibited the growth of K562 cells by terminating the cell cycle at G1 stage and induced apoptosis effectively (Guan et al., 2016). Cinnamon enriched with procyanidin‐B2 decreased the cell multiplication in human prostate cancer cells by inhibiting the activity of 26S proteasome (Gopalakrishnan et al., 2018). Cinnamon with its constituents (procyanidin A), also prevented angiogenesis by regressing the activity of VEGFR2 kinase and by diminishing the VEGF signaling in endothelial cells (Hamidpour et al., 2015).…”