In Vitro Cytotoxicity Evaluation of Plastoquinone Analogues against Colorectal and Breast Cancers along with In Silico Insights

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Ciftci H., Sever B., Bayrak N., Tateishi H., Otsuka M., Fujita M., ...Daha Fazla

PHARMACEUTICALS, cilt.15, sa.10, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 10
  • Basım Tarihi: 2022
  • Doi Numarası: 10.3390/ph15101266
  • Dergi Adı: PHARMACEUTICALS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: colorectal cancer, breast cancer, plastoquinone, NCI-60, growth inhibition, cytotoxicity, apoptosis, DNA binding, pharmacokinetic determinants, DRUG DISCOVERY, RISK, ASSOCIATION, CISPLATIN, APOPTOSIS, INSTITUTE, DESIGN
  • İstanbul Üniversitesi Adresli: Evet

Özet

Colorectal cancer (CRC) and breast cancer are leading causes of death globally, due to significant challenges in detection and management. The late-stage diagnosis and treatment failures require the discovery of potential anticancer agents to achieve a satisfactory therapeutic effect. We have previously reported a series of plastoquinone analogues to understand their cytotoxic profile. Among these derivatives, three of them (AQ-11, AQ-12, and AQ-15) were selected by the National Cancer Institute (NCI) to evaluate their in vitro antiproliferative activity against a panel of 60 human tumor cell lines. AQ-12 exhibited significant antiproliferative activity against HCT-116 CRC and MCF-7 breast cancer cells at a single dose and further five doses. MTT assay was also performed for AQ-12 at different concentrations against these two cells, implying that AQ-12 exerted notable cytotoxicity toward HCT-116 (IC50 = 5.11 +/- 2.14 mu M) and MCF-7 (IC50 = 6.06 +/- 3.09 mu M) cells in comparison with cisplatin (IC50 = 23.68 +/- 6.81 mu M and 19.67 +/- 5.94 mu M, respectively). This compound also augmented apoptosis in HCT-116 (62.30%) and MCF-7 (64.60%) cells comparable to cisplatin (67.30% and 78.80%, respectively). Molecular docking studies showed that AQ-12 bound to DNA, forming hydrogen bonding through the quinone scaffold. In silico pharmacokinetic determinants indicated that AQ-12 demonstrated drug-likeness with a remarkable pharmacokinetic profile for future mechanistic anti-CRC and anti-breast cancer activity studies.