Myricetin induces apoptosis and autophagy in human gastric cancer cells through inhibition of the PI3K/Akt/mTOR pathway

So-Hee Han; Jae-Han Lee; Joong-Seok Woo; Gi-Hwan Jung; Soo-Hyun Jung; Eun-Ji Han; Bumseok Kim; Sung Dae Cho; Jeong Seok Nam; Jeong Hwan Che; Ji-Youn Jung

doi:10.1016/j.heliyon.2022.e09309

Myricetin induces apoptosis and autophagy in human gastric cancer cells through inhibition of the PI3K/Akt/mTOR pathway

Heliyon. 2022 Apr 22;8(5):e09309. doi: 10.1016/j.heliyon.2022.e09309. eCollection 2022 May.

Authors

Affiliations

¹ Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 32439, Republic of Korea.
² College of Veterinary Medicine and Bio-safety Research Institute, Jeonbuk National University, Iksan 54596, Republic of Korea.
³ Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
⁴ Gwangju Institute of Science and Technology, School of Life Sciences, Gwangju 61005, Republic of Korea.
⁵ Biomedical Center for Animal Resource Development, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
⁶ Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.

Abstract

Myricetin, a natural flavonoid present in berries, nuts, and green tea, is well-known for its anticancer properties. Even though several previous studies have reported the anticancer effects induced by myricetin, these effects have not yet been confirmed in the adenocarcinoma gastric cell line (AGS). Moreover, the exact mechanisms of myricetin-induced apoptosis and autophagy have not been clearly identified either. Therefore, in this study, we aimed to examine the role of myricetin in inducing apoptosis and autophagy in AGS gastric cancer cells. First, the survival rate of AGS gastric cancer cells was assessed using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) cell viability assay. Thereafter, the rate of apoptosis was analyzed using4',6-diamidino-2-phenylindole (DAPI) staining as well as annexin V and propidium iodide (PI) staining, and the expression of the proteins associated with apoptosis, PI3K/Akt/mTOR pathway, and autophagy was examined by western blotting. We observed that myricetin reduced the survival rate of AGS gastric cancer cells by inhibiting the PI3K/Akt/mTOR pathway, thereby inducing apoptosis and autophagy. Similar results were also obtained in vivo, and tumor growth was inhibited. Therefore, in the AGS gastric cancer cells, myricetin seems to inhibit the PI3K/Akt/mTOR pathway, which in turn leads to apoptosis in vitroand in vivo, cell-protective autophagy, as well as inhibition of cancer cell proliferation. These results indicate the potential of myricetin as a natural anticancer agent.

Keywords: Apoptosis; Autophagy; Gastric cancer; Myricetin; PI3K/Akt/mTOR pathway; Xenograft.