Honokiol induces autophagy and apoptosis of osteosarcoma through PI3K/Akt/mTOR signaling pathway

Abstract

Honokiol is the main active constituent of Magnolia officinalis. With effective and long‑term pharmacological functions of being antibacterial, anti‑oxidative, anti‑inflammatory, antitumor, anti‑spasmic, anti‑anxiety and anti‑viral, Honokiol is clinically used in the treatment of acute enteritis and chronic gastritis. The aim of the present study was to observe the possible anti‑effects of honokiol on autophagy and apoptosis of osteosarcoma, and to investigate the role of the PI3K/Akt/mTOR signaling pathway in its anticancer effects. MTT assay was used to evaluate cell proliferation and Annexin V‑fluorescein isothiocyanate/propidium iodide staining flow cytometry was used to analyze the apoptotic rate. The authors identified that honokiol could inhibit cell proliferation and induce the apoptotic rate of osteosarcoma cells. The expression level of Bcl‑2‑like protein 4, caspase‑3 and p53 protein expression were induced and cyclin D1 protein expression was suppressed in osteosarcoma cells by honokiol. Autophagy‑associated LC3II protein expression level was promoted, and PI3K, p‑Akt and p‑mTOR protein expression level was suppressed in osteosarcoma cells by honokiol. The present study demonstrated, to the best of the authors' knowledge, for the first time that honokiol induces autophagy and apoptosis of osteosarcoma cells through the PI3K/Akt/mTOR signaling pathway.

Honokiol: A Review of Its Anticancer Potential and Mechanisms

“…Other studies have also shown that honokiol induces autophagy in PC-3 and LNCaP prostate cancer cells via the suppression of mTOR and Akt phosphorylation [77]. Another study revealed that the treatment of neuroblastoma cells with honokiol caused significant downregulation of mTOR phosphorylation, which leads to the induction of autophagy of neuroblastoma cells (neuro-2a cells) through the PI3K/Akt/mTOR signalling pathways [96,195].…”

SIRT3 activator honokiol ameliorates surgery/anesthesia‐induced cognitive decline in mice through anti‐oxidative stress and anti‐inflammatory in hippocampus

“…Recent studies showed that SIRT3 exhibits mighty deacetylase activity and is the key regulator in organ protection under many pathologic states including inflammatory and oxidative stress, acting pivotal roles in development and progression of metabolic diseases including diabetes, neurodegenerative disorders, and other diseases . Honokiol (HNK), [2‐(4‐hydroxy‐3‐prop‐2‐enyl‐phenyl)‐4‐prop‐2‐enyl‐phenol], is a bioactive compound obtained from Magnolia grandiflora which possesses multiple properties including anti‐tumor, anti‐arrhythmic, anti‐thrombocytic, anti‐inflammatory, anti‐angiogenesis, anxiolytic, anti‐oxidative activities in vivo and in vitro . As a potent reactive oxygen species (ROS) scavenger, it is also reported that HNK can enhance the overexpression of SIRT3 to improve antioxidant activity and mitochondrial energy regulation thereby reducing the levels of Aβ and sAPPβ in Chinese Hamster Ovarian (CHO) cells .…”

“…[12][13][14][15] Honokiol (HNK), [2-(4- anti-oxidative activities in vivo and in vitro. [16][17][18][19][20][21] As a potent reactive oxygen species (ROS) scavenger, it is also reported that HNK can enhance the overexpression of SIRT3 to improve antioxidant activity and mitochondrial energy regulation thereby reducing the levels of Aβ and sAPPβ in Chinese Hamster Ovarian (CHO) cells. 22 Additionally, Xian et al suggested that HNK could improve learning and memory impairments induced by scopolamine in mice and attenuate the concentration of prostaglandin E2 and cyclooxygenase-2 level and the neuroinflammatory processes.…”

A Novel Strategy of Dual Inhibition of Distinct Metabolic Features in Osteosarcoma

“…Among the various compounds, pterostilbene (PTE), which is a methylated resveratrol derived from plants, has been shown to inhibit CSC properties in breast cancer [67,68], glioma [69], hepatocellular carcinoma [70], and lung cancer [71] through the inhibition of multiple pathways which are possibly related to the CSC propagation such as Wnt, Hedgehog, Notch, and PI3K/Akt. Honokiol (HNK), which is the extract from Magnolia obovata, has shown its various antitumor effects through the inhibition of several pathways such as PI3K/Akt/mTOR, Wnt, and c-Myc [72][73][74]. Besides these effects of PTE and HNK, we have identified that PTE in combination with HNK could be the possible metabolism-targeted therapy against osteosarcoma as a "two hit" or "dual inhibition" of metabolic pathways, OXPHOS and glycolysis.…”