17-AAG

Purity Level: ≥98.0% (HPLC)

Eukaryotic Cell Culture Applications: Canine osteosarcoma is highly resistant to chemotherapy thus additional information resistance mechanisms is needed. An investigation with 17-AAG in canine osteosarcoma cell lines was undertaken to understand the relationship between cell death, autophagy and mitophagy in regulating cancer cell viability and death. Authors tested 2 cell lines (D22, and D17 from primary and metastatic tumors respectively. It was found that17-AAG caused a simultaneous increase in apoptosis, autophagy, and mitophagy was observed in the D22 cell lines, but only slight apoptosis in the D17 cell line. This study revealed that a treatments based on pro-apoptotic chemotherapy with autophagy regulators could benefit from in-vitro screening, since there are differences in cell responses based on cell type (Massimini et al, 2017).

Cancer Applications: 17-AAG has been shown to induce cell-cycle arrest and apoptosis in cultured ALCL cells irrespective of ALK expression. In addition, 17-AAG has shown promising results in the treatment of uveal melanoma through inhibition of HSP-90 in tandem with c-Kit inhibition.

References:

Hawkins LM, Jayanthan AA, Narendran A (2005)  Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on pediatric acute lymphoblastic leukemia (ALL) with respect to Bcr-Abl status and imatinib mesylate sensitivity. Pediatr Res. 57(3):430-437

Massimini M et al (2017)  17-AAG and apoptosis, autophagy, and mitophagy in canine osteosarcoma cell lines. Vet. Pathol. 54(3):405-412

Radujkovic A et al (2005)  Synergistic activity of imatinib and 17-AAG in imatinib-resistant CML cells overexpressing BCR-ABL--Inhibition of P-glycoprotein function by 17-AAG. Leukemia. 19(7):1198-1206