Tumor Biology

, Volume 37, Issue 11, pp 15053–15063 | Cite as

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
Original Article


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.


Pancreatic cancer NPC-26 Mitochondrion mPTP Gemcitabine 


Compliance with ethical standards

Conflicts of interests


Finance support

Scientific research fund of the First Hospital of Quanzhou Affiliated to Fujian Medical University (20140085).

Supplementary material

13277_2016_5403_MOESM1_ESM.eps (561 kb)
Supplementary Figure 1 HepG2 hepatocellular carcinoma cells and HT-29 colorectal cancer cells were either left untreated (“Ctrl”) or treated with NPC-26 (10 μM) for applied time, cell survival, and apoptosis were analyzed by MTT assay (a) and ssDNA ELISA assay (b), respectively. Data were expressed as mean ± SD, experiments were repeated three times. n = 5 for each assay. *p < 0.05 vs. “Ctrl” group. (EPS 561 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Yang-Yang Dong
    • 1
  • Yi-Huang Zhuang
    • 1
  • Wen-Jie Cai
    • 1
  • Yan Liu
    • 1
  • Wen-Bing Zou
    • 1
  1. 1.Department of Surgical OncologyFirst Hospital of Quanzhou Affiliated to Fujian Medical UniversityQuanzhouChina

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