SYUNZ‐16, a newly synthesized alkannin derivative, induces tumor cells apoptosis and suppresses tumor growth through inhibition of PKB/AKT kinase activity and blockade of AKT/FOXO signal pathway

Abstract

Alkannin is the major bioactive compound of Arnebia euchroma roots, which is used in many therapeutic remedies in Chinese traditional medicine. SYUNZ-16 is a new derivative of alkannin. In this study, anticancer effects of SYUNZ-16 on human lung adenocarcinoma cell line GLC-82 and human hepatocarcinoma cell line Hep3B were tested in vitro. The results showed SYUNZ-16 could obviously inhibit the proliferation of these cancer cell lines via induction of apoptosis, with the evidence of increasing AnnexinV-positive cells and cleaved caspase-3 and PARP fragments. More importantly, we found that SYUNZ-16 could inhibit AKT activity in cell-free system. Treatment of cancer cells with SYUNZ-16 decreased the phosphorylation of AKT. Additionally, SYUNZ-16 partially attenuated the phosphorylation levels of FKHR and FKHRL1 in a dose-dependent and timedependent fashion, and led to an increase in the nuclear accumulation of exogenous FKHR, and upregulated the mRNA expression of Bim and TRADD in cancer cells. Further study showed that constitutively activated AKT1 transfection could reduce apoptosis induction mediated by SYUNZ-16. The in vivo experiments showed that SYUNZ-16 had inhibitory effects on S-180 sarcoma implanted to mice. And in GLC-82 xenograft models, SYUNZ-16 at 20 mg/kg/qod remarkably inhibited the tumor growth with the T/C value of 45.3%. Taken together, SYUNZ-16 might be a potent inhibitor of AKT signaling pathway in tumor cells. These data provide evidence for the development of SYUNZ-16 as a potential antitumor drug candidate for further research and development.

Apogossypolone inhibits the proliferation of LNCaP cells in vitro and in vivo

“…All animal experiments were performed according to the protocol approved by the Fourth Military Medical University Guidelines for the Use and Care of Animals. Tumor growth inhibition (T/C%) values for these in vivo studies were calculated as described previously (13). If the mouse died, the transplanting tumor and its liver, kidney, heart and intestines were removed for histological analysis.…”

Theoretical investigation of the radical scavenging activity of shikonin and acylshikonin derivatives

“…The hydrogen atom transfer for shikonin and acylshikonin derivatives is difficult to obtain compared with phenol, which is generally chosen as the zero compound. However, skikonin and acylshikonin derivatives appear to be good candidates for the one-electron-transfer, particularly for acylshikonin derivatives with thiophene, furan, and 1H-pyrrole groups (1)(2)(3). Their naphthoquinone planar conformation and the extended electronic delocalization between adjacent substituent groups determine low IP values.…”

“…Recently interest on these two compounds increased because of their pharmaceutical activity. They are potent pharmaceutical substances with a well-established and wide spectrum of anticancer [3][4][5][6][7], antibacterial [8], antifungal [9], antiviral [10], antiinflammatory [11], cytotoxic [12], enzyme inhibitor [13,14], antioxidant [15][16][17][18][19], and radical scavenging [20,21] biological activities.…”

Antimicrobial and antioxidant activity of methanol extracts of Arnebia benthamii (Wall ex. G. Don) Johnston—a critically endangered medicinal plant of North western Himalaya

“…Pharmacologically and biologically, the Arnebia spp. were documented to have antibacterial (Singh and Sharma 2012), antitumor (Deng et al 2010), antifungal (Gao 1986), and antiviral-HIV properties (Kashiwada et al 1995). Some reports mentioned that the naphthoquinone derivative, arnebin-1 (b,b-dimethylacrylalkannin), present in Arnebia spp., significantly accelerated wound healing vis-à-vis the inhibiting growth of pathogenic organisms (Sidhu et al 1999).…”