Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle Arrest

Abstract

Prostate cancer is a major cause of cancer-related mortality in men. Even though current therapeutic management has contributed to reducing mortality, additional intervention strategies are warranted to further improve the outcomes. To this end, we have investigated the efficacy of dicaffeoylquinic acids, ingredients in Yerba Mate (Ilex paraguariensis), an evergreen cultivated in South America, the leaves of which are used to prepare a tea/coffee-like drink. Of the various analogs tested, 4,5-dicaffeoylquinic acid (4,5-diCQA) was the most active molecule against DU-145 prostate cancer cells with a 50% inhibitory concentration (IC50) of 5 μM. 4,5-diCQA was active both under normoxic and hypoxic conditions. The effect of 72-hour treatment on DU-145 cells persisted for an extended time period as assessed by clonogenic assay. Mechanistic studies revealed that the toxic effect was not due to induction of programmed cell death but through cell cycle arrest at S phase. Additionally, 4,5-diCQA did not impact PI3K/MAPK signaling pathway nor did it affect the depolarization of the mitochondrial membrane. 4,5-diCQA-induced accumulation of cells in the S-phase also seems to negatively impact Bcl-2 expression. 4,5-diCQA also exhibited inhibitory activity on LNCaP and PC-3 prostate cancer cells suggesting that it has therapeutic potential on a broad range of prostate cancers. Taken together, the novel inhibitory activity and mechanism of action of 4,5-diCQA opens up potential therapeutic options for using this molecule as monotherapy as well as in combinatorial therapies for the clinical management of prostate cancer.

Profiling of Altered Metabolomic States in Bidens pilosa Leaves in Response to Treatment by Methyl Jasmonate and Methyl Salicylate

“…Among the differentially perturbed B. pilosa metabolites were HCA derivatives, identified as significant ions in response to treatment with either elicitor. In previous studies, these groups of secondary metabolites were reported to have various health benefits such as anti-cancer properties [ 50 ], HIV-integrase inhibition by 3,5-di-caffeoylquinic acid [ 51 ] and chicoric acid [ 52 ] and anti-diabetic properties [ 53 , 54 ]. In this study, the di-caffeoylquinic acids, the 4,5-, 3,4- and 3,5- geometric isomers exhibited similar distribution profiles, prominent in the MeJA_12 and the MeSA_24 conditions.…”

Effect of the roasting levels of Coffea arabica L. extracts on their potential antioxidant capacity and antiproliferative activity in human prostate cancer cells

“…42,66 and some studies have shown that hydroxycinnamic acids cause reduction of cell viability and apoptosis of tumour cells. 46,47 Specically, chlorogenic acids and their derivatives have been shown to be able to decrease the number of cells in phases G 0 / G 1 and increase cells in phase S. 69,70 This may explain the observation that green and light roasts caused greater increase in the S phase than did medium roast, because these compounds are degraded during roasting. Probably in dark roast, the amount of chlorogenic acids was not sufficient to have biological effects on cells.…”

Anti-Cancer and Acute Toxicity Activity of Benzo[e]Indol-2- Ylidene)-3 -(4-Methoxyphenyl) Imino Propanal

“…DNA damage, and cell cycle perturbations induced by two representative gold(III) complexes in human leukemic cells with different cisplatin sensitivity [26] .This made 2P effect on the disturb DNA lead to PC3 cell cycle arrest. The effect on the S phase arrest coupled with Bcl-2 down regulation cause anti-proliferation effect to PC3 cell [27] . Melatonin was shown that indole increases neuroendocrine markers and this cause increases cell sensitivity to apoptosis induced by cytokines [28] .…”