Open Access

Anti‑metastatic activity of aromatic aminomethylidenebisphosphonates in a mouse model of 4T1 cell‑derived breast cancer

  • Authors:
    • Anna Nasulewicz-Goldeman
    • Waldemar Goldeman
    • Diana Papiernik
    • Marcin Nowak
    • Ewa Mrówczyńska
    • Joanna Wietrzyk
  • View Affiliations

  • Published online on: May 18, 2023     https://doi.org/10.3892/or.2023.8572
  • Article Number: 135
  • Copyright: © Nasulewicz-Goldeman et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is one of the major causes of cancer‑related mortality among women worldwide. It metastasizes to distant organs, particularly to bone tissue. Nitrogen‑containing bisphosphonates are mainly used as an adjuvant therapy to inhibit skeletal‑related events; however, there is increasing evidence to suggest that these compounds also exert antitumor effects. In previous studies, the authors synthesized two novel aminomethylidenebisphosphonates (BPs), namely benzene‑1,4‑bis[aminomethylidene(bisphosphonic)] acid (WG12399C) and naphthalene‑1,5‑bis[aminomethylidene(bisphosphonic)] acid (WG12592A). Both BPs exhibited notable antiresorptive activity in a mouse model of osteoporosis. The present study aimed to assess the in vivo anticancer activity of WG12399C and WG12592A in 4T1 breast adenocarcinoma model. WG12399C exerted an anti‑metastatic effect by reducing the number of spontaneous lung metastases by ~66% in comparison to the control. In the experimental metastasis model of 4T1‑luc2‑tdTomato cells, this compound reduced the incidence of tumor metastases in the lungs by approximately half in comparison to the control. Both WG12399C and WG12595A also significantly reduced the size and/or number of bone metastatic foci. Their pro‑apoptotic and anti‑proliferative activity may, at least in part, explain the observed effects. Incubation with WG12399C induced an almost 6‑fold increase in caspase‑3 activity in 4T1 cells. Moreover, cells treated with WG12399C or WG12595A exhibited a 2‑fold reduction in invasiveness through Matrigel. Furthermore, both the BPs were able to sensitize the 4T1 cells to cytostatics. In summary, the results of the present study indicate that the examined aminomethylidene‑BPs may be of particular interest in the context of combined treatment in breast cancer therapy.
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July-2023
Volume 50 Issue 1

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Spandidos Publications style
Nasulewicz-Goldeman A, Goldeman W, Papiernik D, Nowak M, Mrówczyńska E and Wietrzyk J: Anti‑metastatic activity of aromatic aminomethylidenebisphosphonates in a mouse model of 4T1 cell‑derived breast cancer. Oncol Rep 50: 135, 2023
APA
Nasulewicz-Goldeman, A., Goldeman, W., Papiernik, D., Nowak, M., Mrówczyńska, E., & Wietrzyk, J. (2023). Anti‑metastatic activity of aromatic aminomethylidenebisphosphonates in a mouse model of 4T1 cell‑derived breast cancer. Oncology Reports, 50, 135. https://doi.org/10.3892/or.2023.8572
MLA
Nasulewicz-Goldeman, A., Goldeman, W., Papiernik, D., Nowak, M., Mrówczyńska, E., Wietrzyk, J."Anti‑metastatic activity of aromatic aminomethylidenebisphosphonates in a mouse model of 4T1 cell‑derived breast cancer". Oncology Reports 50.1 (2023): 135.
Chicago
Nasulewicz-Goldeman, A., Goldeman, W., Papiernik, D., Nowak, M., Mrówczyńska, E., Wietrzyk, J."Anti‑metastatic activity of aromatic aminomethylidenebisphosphonates in a mouse model of 4T1 cell‑derived breast cancer". Oncology Reports 50, no. 1 (2023): 135. https://doi.org/10.3892/or.2023.8572