Encapsulation of cucurbitacin B into lipid polymer hybrid nanocarriers induced apoptosis of MDAMB231 cells through PARP cleavage

BAKAR ATEŞ F., Ozkan E., ŞENGEL TÜRK C. T.

INTERNATIONAL JOURNAL OF PHARMACEUTICS, cilt.586, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 586
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.ijpharm.2020.119565
  • Dergi Adı: INTERNATIONAL JOURNAL OF PHARMACEUTICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Cucurbitacin B, Hybrid nano-carrier, DoE approach, Breast cancer, Apoptosis, SALTS-MIXED MICELLES, DRUG-DELIVERY, LOADED NANOPARTICLES, CAYAPONIA-TAYUYA, IN-VITRO, KAPPA-B, CANCER, PLGA, PROLIFERATION, OPTIMIZATION
  • Ankara Üniversitesi Adresli: Evet

Özet

In the present study, we developed the lipid polymer hybrid nanoparticles of cucurbitacin B (CuB) and evaluated its effects on triple negative breast cancer cells. The 3(2) factorial design was utilized to understand the influence of input variables including PEG-conjugated phospholipid/biodegradable polymer ratio and the total lipids/lecithin molar percentage ratio. The hybrid formulation at the center point of design was specified as optimal hybrid nanocarrier due to its superior features. CuB loaded nanoparticles (CuB-NP) inhibited cell growth through a cell cycle arrest at G0/G1 phase. The studies investigating the efficacy of CuB-NP on apoptosis of cancer cells showed that the annexin v-bound cell population was 20.66 +/- 1.99%, and the depolarized cell population was higher in CuB-NP treated cells. The pro-apoptotic bax, I kappa b-alpha and cleaved PARP levels increased in CuB-NP treated cells, while anti-apoptotic Bcl-2 and NF-kappa B levels decreased. The caspase (+) cell population was higher in nanoparticle-treated group as 14.20 +/- 0.56% and the findings obtained from the caspase assay were also compatible with western blot data. Overall, both CuB and CuB-NP demonstrated anticancer activity, while the lipid polymer hybrid nanoparticle formulation of CuB indicated that the nanoparticle formulation has more promising effect for the treatment of breast cancer.