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The Mitochondrion Interfering Compound NPC-26 Exerts Potent Anti-Pancreatic Cancer Cell Activity in Vitro and in Vivo

The Mitochondrion Interfering Compound NPC-26 Exerts Potent Anti-Pancreatic Cancer Cell Activity in Vitro and in Vivo

Yang-Yang Dong, Yi-Huang Zhuang, Wen-Jie Cai, Yan Liu, Wen-Bing Zou

Tumour Biol. 2016 Nov;37(11):15053-15063.

PMID: 27658776

Abstract:

The development of novel anti-pancreatic cancer agents is extremely important. Here, we investigated the anti-pancreatic cancer activity by NPC-26, a novel mitochondrion interfering compound. We showed that NPC-26 was anti-proliferative and cytotoxic to human pancreatic cancer cells, possibly via inducing caspase-9-dependent cell apoptosis. Pharmacological inhibition or shRNA-mediated silence of caspase-9 attenuated NPC-26-induced pancreatic cancer cell death and apoptosis. Further, NPC-26 treatment led to mitochondrial permeability transition pore (mPTP) opening in the cancer cells, which was evidenced by mitochondrial depolarization, ANT-1(adenine nucleotide translocator-1)-Cyp-D (cyclophilin-D) association and oxidative phosphorylation disturbance. mPTP blockers (cyclosporin and sanglifehrin A) or shRNA-mediated knockdown of key mPTP components (Cyp-D and ANT-1) dramatically attenuated NPC-26-induced pancreatic cancer cell apoptosis. Importantly, we showed that NPC-26, at a low concentration, potentiated gemcitabine-induced mPTP opening and subsequent pancreatic cancer cell apoptosis. In vivo, NPC-26 intraperitoneal injection significantly suppressed the growth of PANC-1 xenograft tumors in nude mice. Meanwhile, NPC-26 sensitized gemcitabine-mediated anti-pancreatic cancer activity in vivo. In summary, the results of this study suggest that NPC-26, alone or together with gemcitabine, potently inhibits pancreatic cancer cells possibly via disrupting mitochondrion.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP864860322	NPC26		864860-32-2	Price

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