Arachidin-1, a Prenylated Stilbenoid from Peanut, Induces Apoptosis in Triple-Negative Breast Cancer Cells

Abstract

Triple-negative breast cancer (TNBC) is unresponsive to typical hormonal treatments, causing it to be one of the deadliest forms of breast cancer. Investigating alternative therapies to increase survival rates for this disease is essential. The goal of this study was to assess cytotoxicity and apoptosis mechanisms of prenylated stilbenoids in TNBC cells. The prenylated stilbenoids arachidin-1 (A-1) and arachidin-3 (A-3) are analogs of resveratrol (RES) produced in peanut upon biotic stress. The anticancer activity of A-1 and A-3 isolated from peanut hairy root cultures was determined in TNBC cell lines MDA-MB-231 and MDA-MB-436. After 24 h of treatment, A-1 exhibited higher cytotoxicity than A-3 and RES with approximately 11-fold and six-fold lower IC50, respectively, in MDA-MB-231 cells, and nine-fold and eight-fold lower IC50, respectively, in MDA-MB-436 cells. A-1 did not show significant cytotoxicity in the non-cancerous cell line MCF-10A. While A-1 blocked cell division in G2-M phases in the TNBC cells, it did not affect cell division in MCF-10A cells. Furthermore, A-1 induced caspase-dependent apoptosis through the intrinsic pathway by activating caspase-9 and PARP cleavage, and inhibiting survivin. In conclusion, A-1 merits further research as a potential lead molecule for the treatment of TNBC.

The cancer preventive activity and mechanisms of prenylated resveratrol and derivatives

“…One possible mechanism is that the prenyl side chain increases the lipophilicity of stilbenoid. The pharmacological activity is modified by enhanced affinity with the lipophilic membrane and improved absorption ( Mohammadhosseinpour et al, 2022 ). Another possible mechanism is that prenylated compounds may inhibit the ras signal transduction.…”

Hairy Root Cultures as a Source of Polyphenolic Antioxidants: Flavonoids, Stilbenoids and Hydrolyzable Tannins

“…Transcripts encoding five enzymes were identified and two of the enzymes were characterized, including AhR4DT-1 that catalyzes prenylation of resveratrol at C-4 to form arachidin-2 [ 192 ]. The prenylated stilbenoids of the peanut manifest an array of interesting biological activities (e.g., anti-inflammatory, antiviral, antioxidant and cytotoxic towards human cancer cells) and have better bioavailability than resveratrol [ 193 , 194 , 195 ]. To achieve higher yields of the prenylated stilbenoids from peanut HRs, the elicitation procedure was further optimized using 125 µM MeJa (signaling molecule implicated in secondary metabolism regulation), 18 g/L cyclodextrin (permeabilizing agent that may trap the product and prevent feedback inhibition), 3 mM H 2 O 2 (inducer of piceatannol production in the HRs of the peanut) and 1 mM MgCl 2 (Mg 2+ as a co-factor of resveratrol prenyltransferases) [ 194 ].…”

Integration of phenylalanine precursor feeding and elicitor treatment in concert with the cellulase-assisted extraction approach to improve stilbene compound production

“…The Ara-1 has attracted increased attention due to the inhibition of PGE2-or NO-mediated in ammation of RAW 264.7 macrophage cells (Djoko et al 2007). Ara-1 has been reported to process anticancer activity in epithelial triple-negative breast cancer (TNBC) cell lines by promoting caspase-dependent cell apoptosis via the intrinsic pathway (Mohammadhosseinpour et al 2022).…”