Extract Derived from Cedrus atlantica Acts as an Antitumor Agent on Hepatocellular Carcinoma Growth In Vitro and In Vivo

Abstract

Cedrus atlantica is widely used in herbal medicine. However, the anti-cancer activity of C. atlantica extract (CAt extract) has not been clarified in hepatocellular carcinoma. In the study, we elucidated the anti-hepatoma capacity of CAt extract on HCC in vitro and in vivo. To explore the anti-hepatoma mechanisms of the CAt extract in vitro, HCC and normal cells were treated with the CAt extract, which showed marked inhibitory effects on HCC cells in a dose-dependent manner; in contrast, the CAt extract treatment was less cytotoxic to normal cells. In addition, our results indicate that the CAt extract induced apoptosis via caspase-dependent and independent apoptosis pathways. Furthermore, the CAt extract inhibited HCC tumor cell growth by restraining cell cycle progression, and it reduced the signaling of the AKT, ERK1/2, and p38 pathways. In the xenograft model, the CAt extract suppressed HCC tumor cell growth and prolonged lifespan by inhibiting PCNA protein expression, repressing part of the VEGF-induced autocrine pathway, and triggering strong expression of cleaved caspase-3, which contributed to cell apoptosis. Moreover, the CAt extract did not induce any obvious changes in pathological morphology or body weight, suggesting it had no toxicity. CAt extract exerted anti-tumor effects on HCC in vitro and in vivo. Thus, CAt extract could be used as a potential anti-cancer therapeutic agent against HCC.

Chemical Composition, Antioxidant, In Vitro and In Situ Antimicrobial, Antibiofilm, and Anti-Insect Activity of Cedar atlantica Essential Oil

“…Atlantic cedar ( Cedar atlantica ) is characterized by wide biological activity, including anti-inflammatory [ 19 ], anticancer [ 20 , 21 ], antioxidant [ 22 ], antimicrobial [ 23 ], and insecticidal [ 24 ] activities. An analgesic effect has also been described [ 25 ].…”

Cedrus atlantica extract exerts antiproliferative effect on colorectal cancer through the induction of cell cycle arrest and apoptosis

“…In the literature, the growth inhibition of C. atlantica is considered to be one of the mechanisms of its anticancer effects. For example, C. atlantica extracts have exhibited inhibitory activity against HepG2 and Mahlavu hepatocellular carcinoma (IC 50 values 27.09 and 33.57 μg/ml, respectively) (Huang et al., 2020 ), DBTRG‐05MG and RG2 glioblastoma (IC 50 value 46.59 and 47.96 μg/ml, respectively) (Chang et al., 2021 ), and K562 chronic myelogenous leukemia (IC 50 value 59.76 μg/ml) (Saab et al., 2012 ) cell lines. In our study, we observed that CAt significantly decreased cell proliferation in HT‐29 and CT‐26 (IC 50 values 31.21 and 19.77 μg/ml, respectively).…”

“…Cedrus atlantica is the largest remaining population and the main forest species in Morocco used for timber production, and sawdust is usually refined by hydrodistillation to provide essential oils. It exerts antimicrobial (Dakir et al., 2005 ; Shin, 2003 ) and anticancer (Chang et al., 2021 ; Huang et al., 2020 ; Saab et al., 2012 ) activities and alleviates pain behavior via inhalation (Martins et al., 2015 ). However, there is currently a lack of information regarding the potential anticancer properties of C. atlantica extract (CAt) against CRC.…”

Acacia catechu seed extract provokes cytotoxicity via apoptosis by intrinsic pathway in HepG2 cells

“…Herbal medicines have been used traditionally to treat various liver‐related ailments, including HCC and its associated symptoms such as nausea and vomiting 8,10 . In previous experimental studies, extracts from different medicinal plants and their derived drugs have been successfully tested against HCC in experimental models 11–16 . In clinical studies, herbal medicines are used to sensitize and potentiate the effects of standard chemotherapeutic drugs by their apoptosis‐inducing and cell cycle inhibition properties 17,18 .…”