Palmitoyl piperidinopiperidine, a novel derivative of 10‑hydroxy‑2‑decenoic acid, as a potent and selective anticancer agent against human colon carcinoma cell lines

  • Authors:
    • Saeko Ando
    • Katsumi Fukamachi
    • Eri Yoshimoto
    • Harutoshi Matsumoto
    • Munekazu Iinuma
    • Masumi Suzui
  • View Affiliations

  • Published online on: December 14, 2020     https://doi.org/10.3892/ijo.2020.5160
  • Pages: 251-265
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The present study, to the best of our knowledge, is the first systematic study of the inhibitory effects of palmitoyl piperidinopiperidine (PPI; Japan Patent no. 5597427), on colon carcinogenesis. PPI exhibited marked growth inhibitory activity in several human colon carcinoma cell lines, with IC50 values of approximately 0.5‑2.2 µM. In silico docking analysis indicated that PPI could bind to the SH2 domain of signal transducer and activator of transcription 3 (STAT3). PPI markedly inhibited the transcriptional activity of the SW837 cell line. Flowcytometric analysis demonstrated that PPI induced an increase in the number of cells in the G1 phase of the cell cycle, and induced sub‑G1 fractions of cells at a higher concentration level of PPI. In the HT29 and SW837 cells, western blot analyses exhibited that in whole cell lysates, PPI induced a marked decrease in the expression levels of p‑STAT3, but not in the levels of STAT3 in these cells. PPI also induced a marked decrease in the expression levels of both STAT3 and p‑STAT3 in the chromatin fraction. In addition, PPI affected the protein expression levels of cyclin D1, p53, Bcl‑2, Bcl‑xL and vascular endothelial growth factor (VEGF). In the HT29 cells, PPI induced a marked and dose‑dependent increase in the expression levels of Bax, cleaved caspase‑3, cleaved caspase‑7, cleaved caspase‑8, cleaved caspase‑9 and cleaved poly (ADP‑ribose) polymerase (PARP). In animal model systems, PPI inhibited the growth of implanted carcinoma cells, and also induced a significant decrease in the multiplicity of colonic aberrant crypt foci. In addition, a marked and dose‑dependent inhibition of angiogenesis of the chick chorioallantoic membrane was observed. As regards the possible molecular mechanisms, it is suggested that the inhibition of STAT3 by PPI may affect the function of molecules that are related to apoptosis, angiogenesis and cell cycle progression, eventually contributing to the PPI‑induced growth inhibitory effects.

Related Articles

Journal Cover

February-2021
Volume 58 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ando S, Fukamachi K, Yoshimoto E, Matsumoto H, Iinuma M and Suzui M: Palmitoyl piperidinopiperidine, a novel derivative of 10‑hydroxy‑2‑decenoic acid, as a potent and selective anticancer agent against human colon carcinoma cell lines. Int J Oncol 58: 251-265, 2021
APA
Ando, S., Fukamachi, K., Yoshimoto, E., Matsumoto, H., Iinuma, M., & Suzui, M. (2021). Palmitoyl piperidinopiperidine, a novel derivative of 10‑hydroxy‑2‑decenoic acid, as a potent and selective anticancer agent against human colon carcinoma cell lines. International Journal of Oncology, 58, 251-265. https://doi.org/10.3892/ijo.2020.5160
MLA
Ando, S., Fukamachi, K., Yoshimoto, E., Matsumoto, H., Iinuma, M., Suzui, M."Palmitoyl piperidinopiperidine, a novel derivative of 10‑hydroxy‑2‑decenoic acid, as a potent and selective anticancer agent against human colon carcinoma cell lines". International Journal of Oncology 58.2 (2021): 251-265.
Chicago
Ando, S., Fukamachi, K., Yoshimoto, E., Matsumoto, H., Iinuma, M., Suzui, M."Palmitoyl piperidinopiperidine, a novel derivative of 10‑hydroxy‑2‑decenoic acid, as a potent and selective anticancer agent against human colon carcinoma cell lines". International Journal of Oncology 58, no. 2 (2021): 251-265. https://doi.org/10.3892/ijo.2020.5160