α-Pinene Enhances the Anticancer Activity of Natural Killer Cells via ERK/AKT Pathway.

Hantae Jo,Haneul Kim,Sofia Brito,Sung Tae Kim,Mi-Gi Lee,Byungsun Cha,Bum-Ho Bin,Byeong Mun Kwak

doi:10.3390/ijms22020656

Abstract

Natural killer (NK) cells are lymphocytes that can directly destroy cancer cells. When NK cells are activated, CD56 and CD107a markers are able to recognize cancer cells and release perforin and granzyme B proteins that induce apoptosis in the targeted cells. In this study, we focused on the role of phytoncides in activating NK cells and promoting anticancer effects. We tested the effects of several phytoncide compounds on NK-92mi cells and demonstrated that α-pinene treatment exhibited higher anticancer effects, as observed by the increased levels of perforin, granzyme B, CD56 and CD107a. Furthermore, α-pinene treatment in NK-92mi cells increased NK cell cytotoxicity in two different cell lines, and immunoblot assays revealed that the ERK/AKT pathway is involved in NK cell cytotoxicity in response to phytoncides. Furthermore, CT-26 colon cancer cells were allografted subcutaneously into BALB/c mice, and α-pinene treatment then inhibited allografted tumor growth. Our findings demonstrate that α-pinene activates NK cells and increases NK cell cytotoxicity, suggesting it is a potential compound for cancer immunotherapy.

Highlights

Natural killer (NK) cells are lymphocytes with a cytotoxic role, possessing an important function in immunity, as they are able to recognize and eliminate virus-infected cells, as well as cancer cells [1]
The results showed that α-pinene, o-cymene and camphor increased perforin mRNA expression in NK-92mi cells compared to the control (phorbol 12-myristate 13-acetate (PMA) and ionomycin treated)
We demonstrate that α-pinene, a terpene originating from phytoncide, enables the ERK and AKT phosphorylation signaling pathways, leading to NK cell activation—observed by increased expressions of CD56 and CD107a (Figure 4)

Summary

Introduction

Natural killer (NK) cells are lymphocytes with a cytotoxic role, possessing an important function in immunity, as they are able to recognize and eliminate virus-infected (or “stressed”) cells, as well as cancer cells [1]. NK cells comprise 10% of the lymphocytes contained in the blood and peripheral lymphoid organs [2], containing abundant cytoplasmic granules and characteristic cell surface markers [3]. When NK cells are activated, they release proteins contained in their granules, such as perforins and granzymes, to attack invasive cells and induce apoptosis. Cancer immunotherapy is a type of strategy for cancer treatment that uses the individual’s natural immune system to combat cancer [5]. Chimeric antigen receptor (CAR)-engineered T (CAR-T) cells are a known treatment with noticeable efficacy in cancer immunotherapy, allowing tumor selectivity and elimination by separating

Methods

Results

Conclusion