Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2

Abstract

Three new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1–3 have been synthesized and fully characterized. 1–3 have similar mononuclear structures with the metal and ligand ratio of 1:2. 1–3 exhibited higher cytotoxicity than the OD ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80–3 and SK-OV-3/DDP cells, with IC50 value of 0.23−4.31 μM. Interestingly, 0.5 μM 1–3 significantly caused HepG2 arrest at S-phase, which was associated with the up-regulation of p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A, PCNA proteins. In addition, 1–3 induced HepG2 apoptosis via a caspase-dependent mitochondrion pathway as evidenced by p53 activation, ROS production, Bax up-regulation and Bcl-2 down-regulation, mitochondrial dysfunction, cytochrome c release, caspase activation and PARP cleavage. Furthermore, 3 inhibited tumor growth in HepG2 xenograft model, and displayed more safety profile in vivo than cisplatin.

Dark‑colored maple syrup treatment induces S‑phase cell cycle arrest via reduced proliferating cell nuclear antigen expression in colorectal cancer cells

“…The present study observed that dark-colored maple syrup treatment decreased PCNA expression, which induced the S-phase cell cycle arrest of DLD-1 cells. Previous reports also indicate that induction of S-phase cell cycle arrest is accompanied by decreased PCNA expression in a number of tumor cells, including in CRC cells treated with functional compounds, such as resveratrol and oxoaporphine metal complexes (51,52). Previous data also indicate that the induction of S-phase cell cycle arrest is associated with changes in the expression of cyclins and CDKs in these cells.…”

Norepinephrine transporter-derived homing peptides enable rapid endocytosis of drug delivery nanovehicles into neuroblastoma cells

“…The stimulation of p53, as one of the key regulators of cell cycle, can induce apoptosis. However, the concurrent Bcl-2 and survivin stimulation suggests at a functional protective mechanisms in the cells [41]. On the other hand, homing via GASNGINAYLC peptide led to up-regulation of p53 together with downregulation of both Bcl-2 and survivin.…”

Achieving the Control of Nonmetallic Inclusions Morphology and Orientation by Electric Current

“…[33][34][35] Electric current causes the fragment of lamellar cementite to be perpendicular to current. [26] Since there is a gap between the new cementite plates, the current flows through the gap, leading in the improvement of conductivity, [20,26] as shown in Figure 12c.…”

“…[24] The numerical calculation shows that the elliptical disk particle with a lower conductivity than liquid tends to rotate in the direction of the electric current, [25] whereas the particle perpendicular to the current direction tends to break into smaller ones. [26] In fact, aggregation and collision of nonmetallic inclusions inevitably occur in the molten metal. However, the model built by Qin or Kolin is based on one single particle.…”