Antiproliferative and Antiestrogenic Activities of Bonediol an Alkyl Catechol fromBonellia macrocarpa

Abstract

The purpose of this study was to investigate antiproliferative activity of bonediol, an alkyl catechol isolated from the Mayan medicinal plant Bonellia macrocarpa. Bonediol was assessed for growth inhibition of androgen-sensitive (LNCaP), androgen-insensitive (PC-3), and metastatic androgen-insensitive (PC-3M) human prostate tumor cells; toxicity on normal cell line (HEK 293) was also evaluated. Hedgehog pathway was evaluated and competitive 3H-estradiol ligand binding assay was performed. Additionally, antioxidant activity on Nrf2-ARE pathway was evaluated. Bonediol induced a growth inhibition on prostate cancer cell lines (IC50 from 8.5 to 20.6 µM). Interestingly, bonediol binds to both estrogen receptors (ERα (2.5 µM) and ERβ (2.1 µM)) and displaces the native ligand E2 (17β-estradiol). No significant activity was found in the Hedgehog pathway. Additionally, activity of bonediol on Nrf2-ARE pathway suggested that bonediol could induce oxidative stress and activation of detoxification enzymes at 1 µM (3.8-fold). We propose that the compound bonediol may serve as a potential chemopreventive treatment with therapeutic potential against prostate cancer.

Effects of medicinal plants and natural compounds in models of prostate cancer related to sex steroids: A systematic review

“…extract (Thelen et al, 2007) increased ERβ mRNA expression. Bonediol (Moo‐Puc et al, 2015), P. africanum extract (Shenouda et al, 2007), and quercetin, baicalein, apigenin, genistein, resveratrol, curcumin, epigallocatechin gallate (Shenouda et al, 2004) were able to bind to ER.…”

“…Although androgen is the main target when dealing with prostate cancer, Huggins and Hodges (1941) also showed that estrogen plays a role in prostate cancer progression. Some medicinal plant extracts ( P. africanum extract [Shenouda et al, 2007], soy milk digestion extract [Kang et al, 2016], B. chinensis extract [Thelen et al, 2007]), and compounds obtained from medicinal plants (bonediol [Moo‐Puc et al, 2015], quercetin, baicalein, apigenin, genistein, resveratrol, curcumin, epigallocatechin gallate [Shenouda et al, 2004], and GBA [Zhang, Kim, et al, 2012]) were able to interact with ER, either by reducing their expression or by directly binding to them. Their binding affinity could be compared with tamoxifen, a drug used in the management of breast cancer that also binds to ER (Sporn & Lippman, 2003), indicating their potential for future studies.…”

Pyrocatechol Alleviates Cisplatin-Induced Acute Kidney Injury by Inhibiting ROS Production

“…We screened a natural product library of 1600 compounds and identified a compound called pyrocatechol that significantly attenuated cisplatin-induced cytotoxicity. Pyrocatechol is a small naturally occurring compound in plants such as Bonellia macrocarpa , Semecarpus anacardium , onions, apples, and olive oil [ 11 , 12 ]. This compound has been utilized in the management of various cancers, including glioblastoma [ 13 ], lung cancer cells [ 14 ], and breast cancer cells [ 15 ].…”

Natural compound catechol induces DNA damage, apoptosis, and G1 cell cycle arrest in breast cancer cells

“…Most of these molecules are known to induce apoptosis and/or regulates cell cycle mechanisms in cancer cells (George, Dellaire, & Rupasinghe, 2017; George, Kumar, Rajkumar, Suresh, & Kumar, 2012; Vazhappilly, Ansari, et al, 2019; Vazhappilly, Saleh, et al, 2019). Catechol is a small naturally occurring compound present in plants such as Semecarpus anacardium , Bonellia macrocarpa , as well as in onions, apples, and olive oil (Moo‐Puc et al, 2015; Nair et al, 2009). Catechol and its derivatives have shown to possess cytotoxicity in glioblastoma and lung cancer cells (de Oliveira et al, 2010; Lim et al, 2016).…”