Candelariella vitellina extract triggers in vitro and in vivo cell death through induction of apoptosis: A novel anticancer agent

Abstract

Candelariella vitellina is common green-yellow lichen found on barks, wood, and rocks in Japanese forests. To investigate the mechanism of its anticancer potential, C. vitellina (80% MeOH/H 2 O) extract was prepared. High-performance liquid chromatography-high-resolution electrospray ionization mass spectrometry analysis revealed seven new compounds and 11 natural compounds of terpenes and polyketides. In vitro cytotoxicity analysis of Caco-2 cells exhibited an IC 50 of 125 ± 4.1 µg/mL. No significant cytotoxicity was observed in vitro in normal human peripheral lymphocytes. Both the IC 25 and IC 50 were determined to explore the potent anticancer potential in this study. C. vitellina exhibited a mitochondrial P53-independent apoptotic effect with negative P53 expression and an elevated BAX/BCL2 ratio as well as upregulated CASP3 mRNA expression. Similarly, in vivo analysis showed the same pattern of anticancer potential but was dependent on the P53 expression. Furthermore, C. vitellina induced antioxidative conditions in vitro and in vivo. The decreased invasion of tumor cells in vivo and increased apoptotic features in vitro and in vivo suggest the moderate to strong apoptotic anticancer potential of C. vitellina. However, further studies are needed to determine the extent and mechanism of action on different cell lines to support the anticancer properties of this lichen.

In Vitro Antigenotoxic, Antihelminthic and Antioxidant Potentials Based on the Extracted Metabolites from Lichen, Candelariella vitellina

“…The in vitro and in vivo anticancer potentials of C. vitellina have been described in a previous study of El-Garawani et al [23], where C. vitellina extract exerted promising antioxidant and pro-apoptotic activities on Caco-2 cells and Ehrlich solid tumor. Moreover, seven novel compounds were detected, and 11 compounds were identified as terpenes and polyketides [23]. The in vitro anti-colorectal cancer, hypocholesterolemic, anti-rota virus activities of C. vitellina extract have been also reported [24].…”

“…In continuation of the previous work of El-Garawani et al [23], lichen was collected from the barks of the trees (Hakozaki, Higashi-ku, Fukuoka-shi, Japan) and identified as Candelariella vitellina. A stock solution of 1:1 (v/v) hydromethanolic extract (80%) of C. vitellina in DMSO was prepared and kept at −4 • C for further biological investigations.…”

Anticancer Potential of Lichens’ Secondary Metabolites

“…Both therapies decreased tumor cell invasion, mitotic activity and increased the formation of apoptotic bodies evaluated using H&E staining and further processed by immunohistochemistry. Notably, mRNA expression of Bax and caspase 3 was decreased and the elevated level of Bcl-2 was detected in solid Ehrlich carcinoma tissue in the treated group [32]. Lichen-derived molecule PHY, isolated from Pseudocyphellaria granulate, inhibited the growth of CT26 xenograft in BALB/c mice.…”

“…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]. Anti-proliferative effects of lichens can be modulated through the regulation of other signaling pathways such as ERK1/2 and AKT [31] or proliferation protein marker Ki-67 [32]. Interestingly, anticancer potential of lichens can also be maintained by modulation of pathways associated with the cancer invasiveness such as c-Met, which acts as mesenchymal epithelial transition factor regulating PI3K/Akt/mTOR, Paxillin/Rac-1, and STATs signaling cascades [33].…”

“…In addition, high concentration of Candelariella vitellina extract reduced the proliferation (Ki-67) and induced apoptosis and necrosis of Caco-2 cells. The extract of C. vitelline decreased Bcl-2 but increased Bax and CASP3 protein levels, so the ratio of Bax/Bcl-2 increased [32]. Anticancer potential of methanol extracts of lichens was evaluated in human lung (H1299, A549) and breast (MDA-MB-231, MCF-7) cancer cell lines.…”