2. Academic Validation
  3. Tenacissoside G synergistically potentiates inhibitory effects of 5-fluorouracil to human colorectal cancer

Tenacissoside G synergistically potentiates inhibitory effects of 5-fluorouracil to human colorectal cancer

  • Phytomedicine. 2021 Jun:86:153553. doi: 10.1016/j.phymed.2021.153553.
Kaichun Wang 1,  Wei Liu 2,  Qinfen Xu 1,  Chao Gu 1,  Daode Hu 3
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
  • 2 Department of Clinical Pharmacology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China.
  • 3 Department of Clinical Pharmacology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address: [email protected].
PMID: 33906076 DOI: 10.1016/j.phymed.2021.153553
Abstract

Background: Colorectal Cancer (CRC) is one of the most malignant tumors worldwide with poor prognosis and low survival rate. Since the clinical efficacy of the commonly used 5-fluorouracil (5-FU) based chemotherapy in CRC patients is limited because of its intolerable adverse effects, there is an urgent need to explore agents that can enhance the anti-cancer activity of 5-FU, reduce adverse effects and prevent resistance.

Purpose: This study aims to investigate Tenacissoside G (TG)'s synergistic potentiation with 5-FU in inhibitory activity to colorectal Cancer cells.

Methods: The anti-proliferation effect of TG on 5 colorectal Cancer cell lines was assessed by CCK-8 assay. The isobologram analysis and combination index methods were used to detect the synergistic effect of TG and 5-FU by the CompuSyn software using the T.C. Chou Method. The effects of TG/5-FU combination on cell cycle distribution and Apoptosis induction were detected by flow cytometry. DNA damage degrees of cells treated with TG, 5-FU and their combination were evaluated by the alkaline comet assay. Protein expression regulated by the TG/5-FU combination was investigated by western blotting. Furthermore, a xenograft mouse model was established to investigate the synergistic anti-tumor effect in vivo.

Results: In this work, we observed a dose-dependent growth inhibitory activity and cell cycle arrest induction of TG, a monomeric substance originated from Marsdenia tenacissima (Roxb.) Wight et Arn, in colorectal Cancer cells. It was found that TG potentiated the Anticancer effects of 5-FU with a synergism for the first time. And the co-treatment effects were also validated by in vivo experiments. The underlying mechanisms involved in the synergistic effects were probably included: (1) increased activation of Caspase cascade; (2) enhancement of DNA damage degree and (3) induction of p53 phosphorylation at Serine 46.

Conclusion: TG potentiated 5-FU's inhibitory activity to human colorectal Cancer through arresting cell cycle progression and inducing p53-mediated Apoptosis, which may present a novel strategy in CRC therapies and contribute to the optimizing clinical application of 5-FU.

Keywords

5-Fluorouracil; Apoptosis; Colorectal cancer; Synergism; Tenacissoside G.

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