Anticancer Effects of α-Pinene in AGS Gastric Cancer Cells

J Med Food. 2024 Apr;27(4):330-338. doi: 10.1089/jmf.2023.K.0267. Epub 2024 Feb 22.

Abstract

Gastric cancer is the fifth most common cancer globally and the third leading cause of cancer-related mortality. Existing treatment strategies for gastric cancer often present numerous side effects. Consequently, recent studies have shifted toward devising new treatments grounded in safer natural substances. α-Pinene, a natural terpene found in the essential oils of various plants, such as Lavender angustifolia and Satureja myrtifolia, displays antioxidant, antibiotic, and anticancer properties. Yet, its impact on gastric cancer remains unexplored. This research assessed the effects of α-pinene in vitro using a human gastric adenocarcinoma cell-line (AGS) human gastric cancer cells and in vivo via a xenograft mouse model. The survival rate of AGS cells treated with α-pinene was notably lower than that of the control group, as revealed by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. This decline in cell viability was linked to apoptosis, as verified by 4',6-diamidino-2-phenylindole and annexin V/propidium iodide staining. The α-pinene-treated group exhibited elevated cleaved-poly (ADP-ribose) polymerase and B cell lymphoma 2 (Bcl-2)-associated X (Bax) levels and reduced Bcl-2 levels compared with the control levels. Moreover, α-pinene triggered the activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 within the mitogen-activated protein kinase (MAPK) pathway. In the xenograft mouse model, α-pinene induced apoptosis through the MAPK pathway, devoid of toxicity. These findings position α-pinene as a promising natural therapeutic for gastric cancer.

Keywords: MAPK pathway; anticancer effects; apoptosis; gastric cancer; xenograft mouse model; α-pinene.

MeSH terms

  • Animals
  • Apoptosis
  • Bicyclic Monoterpenes*
  • Cell Line, Tumor
  • Cell Proliferation
  • Extracellular Signal-Regulated MAP Kinases
  • Humans
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology

Substances

  • alpha-pinene
  • Extracellular Signal-Regulated MAP Kinases
  • Proto-Oncogene Proteins c-bcl-2
  • Bicyclic Monoterpenes