Novel glycosylation zinc(II)-cryptolepine complexes perturb mitophagy pathways and trigger cancer cell apoptosis and autophagy in SK-OV-3/DDP cells.

With the aim of shedding some light on the mechanism of action of zinc(II) complexes in antiproliferative processes and molecular signaling pathways, three novel glycosylated zinc(II)-cryptolepine complexes, i.e., [Zn(QA1)Cl2] (Zn(QA1)), [Zn(QA2)Cl2] (Zn(QA2)), and [Zn(QA3)Cl2] (Zn(QA3)), were prepared by conjugating a glucose moiety with cryptolepine, followed by complexation of the resulting glycosylated cryptolepine compounds N-((1-(2-morpholinoethyl)-1H-1,2,3-triazol-4-yl)methyl)-benzofuro[3,2-b]quinolin-11-amine (QA1), 2-(4-((benzofuro[3,2-b]quinolin-11-ylamino)methyl)-1H-1,2,3-triazol-1-yl)ethan-1-ol (QA2), and (2S,3S,4R,5R,6S)-2-(4-((benzofuro[3,2-b]quinolin-11-ylamino)-methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (QA3) with zinc(II), and their anticancer activity was evaluated. In MTT assays, Zn(QA1)-Zn(QA3) were more active against cisplatin-resistant ovarian SK-OV-3/DDP cancer cells (SK-OV-3cis) than ZnCl2 and the QA1-QA3 ligands, with IC50 values of 1.81 ± 0.50, 2.92 ± 0.32, and 1.01 ± 0.11 µM, respectively. Complexation of glycosylated cryptolepine QA3 with zinc(II) increased the antiproliferative activity of the ligand, suggesting that Zn(QA3) could act as a chaperone to deliver the active ligand intracellularly, in contrast with other cryptolepine metal complexes previously reported. In vivo and in vitro investigations suggested that Zn(QA3) exhibited enhanced anticancer activity with treatment effects comparable to those of the clinical drug cisplatin. Furthermore, Zn(QA1)-Zn(QA3) triggered SK-OV-3cis cell apoptosis through mitophagy pathways in the order Zn(QA1) > Zn(QA1) > Zn(QA2). These results demonstrate the potential of glycosylated zinc(II)-cryptolepine complexes for the development of chemotherapy drugs against cisplatin-resistant SK-OV-3cis cells.

Management of Schwannoma in the hepatoduodenal ligament: A case report and review of the literature.

RATIONALE: Schwannomas are neoplasms that originate from Schwann cells of the peripheral nerve sheath with a low malignant potential. Considering that Schwannomas often occur in the upper extremities, trunk, head, and neck, but in the hepatoduodenal ligament has seldom been reported. PATIENT CONCERNS: A 70-year-old man was referred to our hospital for further evaluation of distension in upper abdomen. Abdominal ultrasonography reported that an anechoic mass was found between the pancreatic head and portal vein, which was measured to be about 5.5 × 4 × 4 cm. No blood flow signal was found within the mass by color doppler ultrasound. Subsequently, abdominal contrast enhanced computed tomography revealed that a well-defined round soft-tissue was above the pancreatic head and adjacent to the common heapatic artery, and it had no obvious enhancement in the arterial phase and portal phase. DIAGNOSES: Schwannomas in the hepatoduodenal ligament. INTERVENTIONS: After the work-up of a multidisciplinary team, a right complete excision was carried out and schwannoma was diagnosed by pathology. OUTCOMES: The patient's postoperative course was uneventful, and he left the hospital 10 days after the operation. Additionally, at the time of writing, recurrence was not observed with a follow-up of 17 months. LESSONS: schwannomas in the hepatoduodenal ligament are extremely rare with benign behavior. Surgical resection is the gateway to cure it; however, accurate preoperative diagnosis of the schwannomas in the hepatoduodenal ligament is a huge challenge because neither the clinical symptoms nor the imaging manifestations are specific.