Essential Oil from Pinus Koraiensis Pinecones Inhibits Gastric Cancer Cells via the HIPPO/YAP Signaling Pathway

Abstract

Pinecone is a traditional folk herb, which has been used in China for many years. In this paper, the essential oil from Pinus koraiensis pinecones (PEO) was obtained by hydrodistillation and 41 compounds were identified by gas chromatography–mass spectrometry (GC-MS), mainly including α-Pinene (40.91%), Limonene (24.82%), and β-Pinene (7.04%). The purpose of this study was to investigate the anti-tumor activity of PEO on MGC-803 cells and its mechanism. Anti-tumor experiments in vitro showed PEO could significantly inhibit the proliferation and migration of MGC-803 cells, and it also could arrest the cell cycle in the G2/M phase, decrease the mitochondrial membrane potential, and induce apoptosis. Finally, the effects of PEO on genes expression on MGC-803 cells were analyzed by RNA sequencing, and results showed that after treatment with PEO, 100 genes were up-regulated, and 57 genes were down-regulated. According to the KEGG pathway and GSEA, FAT4, STK3, LATS2, YAP1, and AJUBA were down-regulated, which were related to HIPPO signaling pathway. Real-time PCR and western blot further confirmed the results of RNA sequencing. These results indicated that PEO may exert anti-tumor activity via the HIPPO/YAP signaling pathway. The anti-tumor mechanism of this oil can be further studied, which is important for the development of anti-tumor drugs.

Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

“…We demonstrated that PMEO induces apoptosis in human prostate cancer cells without affecting the viability of non-transformed human fibroblasts. The anticancer activities of EOs from two other pine species were described earlier [ 36 , 37 ]. Ren et al (2018) reported that Pinus densiflora needles EO suppressed tumor growth in an MCF-7 xenograft mouse model by regulating the AMPK/mTOR signaling pathway [ 36 ].…”

Cyperus articulatus L. (Cyperaceae) Rhizome Essential Oil Causes Cell Cycle Arrest in the G2/M Phase and Cell Death in HepG2 Cells and Inhibits the Development of Tumors in a Xenograft Model

“…The EO from Pinus koraiensis (Pinaceae) also arrested the cell cycle in the G 2 /M phase and induced cell death in gastric adenocarcinoma MGC-803 cells. The main chemical constituents were α-pinene, limonene and β-pinene [37]. The EO from the leaves of Melaleuca alternifolia (Myrtaceae) arrested the cell cycle in the G 2 /M phase, causing cell death in human melanoma A-375 cells and squamous cell carcinoma HEp-2 cells [38].…”

Natural Phytochemicals Derived from Gymnosperms in the Prevention and Treatment of Cancers

“…Pinenes have good anticancer activity, arrest the cell cycle in the G2/M phase, and inhibit hepatoma cell proliferation [ 14 ]. Pinus koraiensis essential oils, mainly consisting of α-pinene, stop the proliferation and migration of human gastric carcinoma cells (MGC-803) and induce apoptosis [ 89 ]. This is due to its effect on the Hippo signaling pathway, known as the tumor suppressor, which has been extensively studied [ 112 ].…”

“…In this pathway, the phosphorylation of YAP occurs and inhibits the migration and proliferation of tumor cells [ 113 ]. α-Pinene can decrease the expression of YAP, leading to the inhibition of cancer cells and the induction of apoptosis [ 89 ].…”