APS8, a synthetic analog of naturally occuring poly-APS with defined alkyl chain length and molecular size, non-competitively inhibits α7 nicotinic acetylcholine receptors (nAChRs) at nanomolar concentrations that are too low to be generally cytotoxic. In the present study we show that APS8 inhibits NSCLC tumor cell growth and activates apoptotic pathways. APS8 was not toxic for normal lung fibroblasts. Furthermore, in NSCLC cells, APS8 reduced the adverse anti-apoptotic, proliferative effects of nicotine. Our results suggest that APS8 or similar compounds might be considered as lead compounds to develop antitumor therapeutic agents for at least certain types of lung cancer.
COBISS.SI-ID: 2854223
Human lung A549 xenograft tumors were induced by subcutaneously injection of cell suspension (107 cells/100 µl) in the right flank of SCID mice. When tumors were grown up to 40 mm3, mice were treated with intratumoral or intravenous injection of APS8 (2 mg/kg and 4mg/kg). Antitumor effectiveness was assessed by tumor growth delay assay. Treatment of mice bearing A549 tumors with intratumoral administration of APS8 at the dose of 4 mg/kg showed good antitumor effect resulting in tumor growth delay of 26 days compared to the control group. Systemic treatments and intratumoral treatment with lower dose of APS8 did not result in significant tumor growth delay. Treatment with polyAPS8 at the selected doses did not result in any systemic or local side effects. The results of our preliminary study demonstrate that local administration of APS8 has good antitumor effect on human lung xenograft A549 tumors.
COBISS.SI-ID: 1510779