Effects of anti-proliferative lichen metabolite, protolichesterinic acid on fatty acid synthase, cell signalling and drug response in breast cancer cells

Protolichesterinic acid enhances doxorubicin-induced apoptosis in HeLa cells in vitro

“…It also promotes apoptosis and necrosis in healthy tissue causing toxicity in the brain, liver, kidney and heart [36]. with protolichesterinic acid [37]. In SK-BR-3 cells synergic effect of protolichesterinic acid was associated to down-regulation of fatty acid synthase with secondary effects on HER2 expression and signalling [37].…”

“…with protolichesterinic acid [37]. In SK-BR-3 cells synergic effect of protolichesterinic acid was associated to down-regulation of fatty acid synthase with secondary effects on HER2 expression and signalling [37]. Enhanced sensitivity to temozolomide by co-treatment with lobarstin, a metabolite occurring from the Antarctic lichen Stereocaulon alpinum, was described in human glioblastoma T98G cells and was attributed to reduced DNA repair [38].…”

Recent Progress in HER2 Associated Breast Cancer

“…The concept of targeting more than 1 ErbB family member using multiple agents in the treatment of HER2-positive BC has been shown in preclinical studies (Bessadottir et al, 2014;Kumler et al, 2014), for combinations of HER2-directed agents may show additive or synergistic effect and give more hope for cure compared to the traditional sequential approach Trastuzumab combined with carboplatin and paclitaxel improve tumor response rates and prolong the time-to-progression (Shinde et al, 2015); trastuzumab combined with AKT investigational allosteric inhibitor MK-2206 inhibit compensatory signaling (Hudis et al, 2013). Dual HER2-targeting with lapatinib.…”

“…Totally, combination of trastuzumab plus lapatinib and trastuzumab plus pertuzumab, respectively, offered the first evidence of dual targeting being superior to single agent therapy with trastuzumab (Pazhoomand et al, 2013;Kumler et al, 2014), and more surprisingly, a recent study indicates that by using targeted therapies in a sequential order, starting with two anti-HER2 drugs, followed by treatment with an anti-HER2 drug and a PI3K/mTOR inhibitor and lastly combining all three agents can prolong survival and minimize toxic effects in mouse models bearing aggressive breast tumours (Zhang et al, 2011;Bessadottir et al, 2014).…”

Anti-proliferative and pro-apoptotic effects of lichen-derived compound protolichesterinic acid are not mediated by its lipoxygenase-inhibitory activity

“…The lichen material was identified by Dr. Hordur Kristinsson, lichenologist, and a voucher specimen LA-31128, is deposited at the Icelandic Natural History Museum, Akureyri. Isolation and identification of (þ )-protolichesterinic acid (PA) was performed as described [28] to 97% purity. The structure of PA was further confirmed by UPLC-Quadrupole Time of Flight Mass Spectrometer (Waters Synapt G1 Mass Spectrometer, Waters, Manchester, UK; Fig.…”