ArticleDrug design, development and therapy2017
Investigating isoquinoline derivatives for inhibition of inhibitor of apoptosis proteins for ovarian cancer treatment.
Article in Drug design, development and therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 11 citations in OpenAlex.
- Tanshinol inhibits the growth, migration and invasion of hepatocellular carcinoma cells via regulating the PI3K-AKT signaling pathway.OncoTargets and therapy · 2019Article
- SPARCL1 suppresses the proliferation and migration of human ovarian cancer cells via the MEK/ERK signaling.Experimental and therapeutic medicine · 2018Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
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Abstract
objectiveTo discover novel isoquinoline derivatives for inhibition of inhibitor of apoptosis proteins (IAP) for the treatment of ovarian cancer.
methodsWe first synthesized 533 isoquinoline derivatives, and screened them using CCK-8 to measure their antiproliferative activity. These compounds were further tested by Hoechst staining and flow cytometric analysis to assess proapoptotic activity. The in vivo antitumor efficacy and safety of the screened compounds were evaluated on the xenograft mouse model. Ki-67 staining and TUNEL assay were used to evaluate proliferation and apoptosis in the resected tumors, respectively. Western blot and polymerase chain reaction (PCR) were conducted to evaluate the levels of proliferating cell nuclear antigen (PCNA), caspase-3, PARP, and IAP in resected tumors.
resultsCompound B01002 and C26001 displayed antiproliferative and proapoptotic activity on SKOV3 ovarian cancer with an IC50 of 7.65 and 11.68 µg/mL, respectively. Both compounds inhibited tumor growth in a xenografted mouse model with good safety profiles, and tumor growth inhibition (TGI) of B01002 and C26001 was 99.53% and 84.23%, respectively. Resected tumors showed that both compounds inhibited tumor cell proliferation and induced apoptosis in vivo. Caspase-3 and PARP were activated, whereas IAP proteins were downregulated at the protein level.
conclusionCompound B01002 and C26001 could inhibit ovarian tumor growth and promote tumor apoptosis, partly by downregulating the IAPs, and, thus, might be promising candidates for treatment of ovarian cancer.
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