Changes in apoptosis-related gene expression profiles in cancer cell lines exposed to usnic acid lichen secondary metabolite

Abstract

The presence of uninhibited side effects of cancer drugs often used in cancer treatment has stimulated the search for alternative therapeutic approaches. Therefore, anticarcinogenic effects of synthetic, herbal, and fungal drugs have been investigated for the treatment of various cancer types in recent studies. Lichens, symbiotic organisms of fungi and algae, synthesize metabolites with significant biological activities. The aim of the current study was to screen the anticancer potential of usnic acid on various types of nonmalignant cell lines (Vero, L929) and cancer cell lines (CaCo2, RD, Hep2C, HepG2, Wehi). The growth inhibitory effect of usnic acid was determined by MTT assay. Since this study was also designed to explore mRNA expression profiles, this paper is the first to look into the effects of usnic acid on apoptotic gene expression. The effects of usnic acid on the gene expression patterns of the tumor suppressor gene p53, proapoptotic gene Bcl-2, and Bax were studied with qRT-PCR. There was an approximately ninefold decrease in the p53 and Bcl-2 expression for usnic acid in the Wehi cancer cell line. Consequently, it is concluded that usnic acid has tumor inhibitory properties, and if indicated by further works like animal studies and clinical trials, it may be used therapeutically in the future.

Oxidative stress mediated by gyrophoric acid from the lichen Umbilicaria hirsuta affected apoptosis and stress/survival pathways in HeLa cells

“…Using MTS tests, we observed cytotoxic effect of GA against three different cell lines. Through HeLa cells were most sensitive and therefore used for further experiments; both our experiments and literature data [1,4,25] indicate activity against a very broad spectrum of carcinoma cells in dose-dependent manner.…”

Anticancer Potential of Lichens’ Secondary Metabolites

“…Both natural and commercial UA had similar cytotoxicity on cancer cells but no significant effect in non-malignant L929 and Vero cells. Indeed, UA increased the expression of Bax and decreased the expression of Bcl-2 and p53 genes in cancer but not in non-malignant cells [29]. Additionally, the concentration of UA at 8 µM, inhibited SCF-mediated migration of human colorectal cancer (HCT116, LS174 c-KIT+) cells.…”

“…In regard to programmed cell death, lichens act as activators of apoptosis in various cancer cells [21,26] through the modulation of gene expression of products related to apoptosis such as caspases, p53, p38, or anti-/pro-apoptotic proteins of Bcl-2 family [29]. Induction of apoptosis by lichens might be associated also with an increase of cleaved PARP, a stress response protein repairing damaged DNA and regulating chromatin structure [30], with inactivation of the mammalian target of rapamycin (mTOR) or activation of c-Jun N-terminal kinase (JNK) signaling [27].…”

“…In this regard, metastasis-related genes including CAPN1, CDC42, CFL1, IGF1, or WASF1 as well as epithelial-mesenchymal markers (Twist, Snail, Snug) might also be targets of lichens. On the other hand, anticancer effect of lichen realized through the angiogenesis inhibitory activities are related to the suppression of endothelial tube formation [35] or vascular endothelial growth factor receptor (VEGFR)-2-mediated Akt and extracellular signal-regulated kinase (ERK) signaling [29]. Current results showed that anticancer effects of lichens are also associated with the modulation of inflammatory responses via TNF-α, IL-1β, IL-6, and TGF-β1 [36] and with targeting of microRNA molecules [37].…”

Evaluation of in vitro Anticancer Activity of Vulpinic Acid and its Apoptotic Potential Using Gene Expression and Protein Analysis

“…Usnic acid and its enantiomers are the most extensively studied lichen secondary metabolites. 17,18,19 Vulpinic acid has also been examined for malignant mesothelioma cells MM98, vulvar carcinoma cells A431 and Keratinocytes HaCaT cells by Burlando et al 20 According to their study results, vulpinic acid extracted from Letharia vulpine shows minimum toxic effect when compared with usnic acid, salazinic, gyrophoric and evernic acid.…”