Integrated transcriptome and in vitro analysis revealed anti-proliferative effect of citral in human stomach cancer through apoptosis

Abstract

Cancer is the second leading cause of death globally, particularly stomach cancer is third most common causes of cancer death worldwide. Citral possesses anti-tumor activity in various cancer cell lines, However its effect toward stomach cancer and its mechanism of action is have yet to be elucidated. The goal of the present study is to elucidate the role of citral in stomach cancer using transcriptome and in vitro approaches. We performed transcriptome analysis using RNA-seq and explored its capability to persuade apoptosis in AGS human stomach cancer cell lines in vitro. Furthermore, the enrichment and KEGG pathway results suggested that there are several genes involved to induce apoptosis pathway. Furthermore, our study also demonstrated that citral arrested colony formation and migration of cancer cells significantly than that of untreated cells. RNA-seq revealed a total of 125 million trimmed reads obtained from both control and citral treated groups respectively. A total number of 612 differentially expressed genes (DEGs) were identified which includes 216 genes up-regulated and 396 genes down-regulated genes after treatment. The enrichment analysis identified DEGs genes from transcriptome libraries including cell death, cell cycle, apoptosis and cell growth. The present study showed the significant inhibition effect upon citral by regulating various genes involved in signaling pathways, inhibits metastasis, colony formation and induced apoptosis both in silico and in vitro.

A Narrative Review of the Antitumor Activity of Monoterpenes from Essential Oils: An Update

“…Citral had an antiproliferative effect on several cancer cells. Apoptosis was observed in human stomach cancer cells [ 54 ]; in prostate cancer cells (PC3 cells) through upregulating BAX and downregulating Bcl-2 expression [ 55 ]; and in HCT116 and HT29 (colorectal cancer cell lines), in which it induced mitochondrial-mediated apoptosis via increased intracellular ROS and phosphorylation of p53 protein and the expression of Bax and decreased expression of Bcl-2 and Bcl-xL which promoted the cleavage of caspase-3 [ 56 ]; and citral also showed cytotoxicity in Burkitt's lymphoma cell line human and additively increased the cytotoxic and apoptotic effects of doxorubicin [ 57 ]. The combination of citral and doxorubicin increased the expression of the proapoptotic protein BAK but decreased the expression of the antiapoptotic protein BCL-XL compared to cells just treated with doxorubicin [ 57 ].…”

Phytochemical Analysis and In Vitro Cytotoxic Activity against Colorectal Adenocarcinoma Cells of Hippophae rhamnodies L., Cymbopogon citratus (D.C.) Stapf, and Ocimum basilicum L. Essential Oils

“…Regarding Cc_EO composition (Table 2), the primary phytochemical constituents are alpha-and beta-citral (37.23% and 28.91%, respectively). Citral is a natural compound possessing well-defined anti-tumor properties, especially in the case of breast carcinoma, stomach, and prostate cancers by inducing apoptosis and inhibiting metastasis [27][28][29][30]. Cc_EO exerted a strong in vitro anti-CRC effect at 75 µg/mL, in terms of cellular viability which decreased to 62.69% in Caco-2 cells and 46.58% in HT-29 cells following the 48 h treatment (Figure 2).…”

Methanol Extract of Aerial Parts of Pavetta indica L. Enhances the Cytotoxic Effect of Doxorubicin and Induces Radiation Sensitization in MDA-MB-231 Triple-Negative Breast Cancer Cells

“…Fernando et al found that stigmast-5-en-3-ol from Dendronephthya gigantea exerted proapoptotic and anti-proliferative effects on MCF-7 human breast cancer cells [42]. Additionally, citral has been shown to inhibit the proliferation of breast cancer [43] and stomach cancer [44] cells. Moreover, by reducing the expression of glutathione, a Reactive Oxygen Species (ROS) scavenger, citral activates apoptosis of breast cancer cells [43], and in combination with curcumin, induces their apoptosis and cell cycle arrest [45].…”