Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway

Abstract

Abstract. The present study aimed to determine whether maslinic acid effectively inhibits the proliferation of MKN28 cells, and to investigate the mechanisms underlying its antitumor functions. MKN28 cell viability was evaluated using a Cell Counting Kit-8, cell proliferation was analyzed by a colony formation assay and flow cytometry was used to investigate the rate of apoptosis. Western blot analysis was performed in order to determine the differential expression levels of Janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3) and apoptosis associated proteins B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax) and Bcl-2 associated agonist of cell death (Bad). Interleukin-6 (IL-6) concentration was evaluated using ELISA. IL-6 and anti-IL-6 antibodies were used to investigate the role of IL-6 in MKN28 cells treated with maslinic acid proliferation, and the STAT3 phosphorylation rates. The results demonstrated that maslinic acid treatment significantly reduced cell proliferation, induced apoptosis and was accompanied by a significant decrease in Bcl-2, Bax and Bad expression levels. Maslinic acid treatment also resulted in the downregulation of phosphorylated-STAT3 and JAK2, and significantly inhibited the protein expression of IL-6. Maslinic acid is able to inhibit MKN28 cell proliferation and the phosphorylation of STAT3 by downregulating the expression of IL-6. These results suggest that maslinic acid suppresses the growth of MKN28 cells by inducing apoptosis via its inhibition of the IL-6/JAK/STAT3 signaling cascade.

Activation of spinal dorsal horn P2Y₁₃ receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain

“… 33 , 34 IL-6 is one of the most prevalent cytokines that mediates its effects via the phosphorylation of STAT3. 35 In addition, Dominguez et al reported that intrathecal administration of IL-6 to naive rats rapidly activated microglial JAK/STAT3 and induced downstream changes that closely resemble controlled cortical impact (CCI)-evoked alterations. 36 Thus, we have reason to speculate the possible role of the P2Y 13 receptor in IL-6 production as well as the elevated activation of JAK2/STAT3 signaling in the development of DNP.…”

The compound 2‐(naphthalene‐2‐thio)‐5,8‐dimethoxy‐1,4‐naphthoquinone induces apoptosis via reactive oxygen species‐regulated mitogen‐activated protein kinase, protein kinase B, and signal transducer and activator of transcription 3 signaling in human gastric cancer cells

“…In addition, Akt may regulate apoptosis via modulation of Bcl‐2 family members (Zhang et al, ). The STAT3 signaling pathway is also a key anti‐apoptotic pathway in cancer cells because it is associated with cell proliferation, immune evasion, and apoptotic arrest (Liu et al, ; Wang, Tang, & Zhang, ). These effects are most likely mediated through ROS‐induced activation of the STAT3 pathway (Miao, Yu, Ren, & Yang, 2017).…”

“…The STAT3 signaling pathway is also a key anti-apoptotic pathway in cancer cells because it is associated with cell proliferation, immune evasion, and apoptotic arrest (Liu et al, 2015;Wang, Tang, & Zhang, 2017).…”

Maslinic acid induces autophagy by down‐regulating HSPA8 in pancreatic cancer cells

“…MA (2‐α, 3‐β‐dihydroxyolean‐12‐en‐28‐oic acid, Figure a) is a pentacyclic triterpene acid widely distributed in dietary plants, especially abundant in olive fruit skins (Lozano‐Mena, Sanchez‐Gonzalez, Juan, & Planas, ). In the past years, MA has attracted much interest due to its proven pharmacological safety (Sanchez‐Gonzalez, Lozano‐Mena, Juan, Garcia‐Granados, & Planas, ), and various biological activities such as antitumor (Wang, Tang, & Zhang, ), antiinflammation (Fukumitsu, Villareal, Fujitsuka, Aida, & Isoda, ), antivirus (Mooi, Wahab, Lajis, & Ali, ), anti‐oxidation (Mkhwanazi, Serumula, Myburg, Van Heerden, & Musabayane, ), and antidiabetic activities(Guan et al, ). The cytotoxic activity of MA has been extensively studied in recent years.…”