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Deoxypodophyllotoxin induces cell cycle arrest and apoptosis in human cholangiocarcinoma cells

Meifang Xiao1, Xuegong Fan2, Yongming Fu2

  • 1Department of Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Oncology Letters
|August 22, 2018
PubMed

Insights

Deoxypodophyllotoxin (DPT) exhibits anticancer properties by inhibiting human cholangiocarcinoma cell proliferation. DPT induces cell cycle arrest and apoptosis, suggesting its potential as a novel therapeutic agent.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • Deoxypodophyllotoxin (DPT) is a natural flavolignan with known anti-inflammatory, anti-viral, and anticancer activities.
  • Cholangiocarcinoma is a challenging cancer with limited effective treatment options.

Purpose of the Study:

  • To investigate the anti-proliferative effects of Deoxypodophyllotoxin (DPT) on human cholangiocarcinoma cell lines (QBC939 and RBE).
  • To elucidate the underlying mechanisms by which DPT induces cytotoxicity in these cancer cells.

Main Methods:

  • Cell viability was assessed using MTT assays to determine the dose- and time-dependent effects of DPT.
  • Cell cycle progression was analyzed, focusing on the G2/M phase, and protein expression of Cyclin B and cyclin-dependent kinase 1 was evaluated.
  • Apoptosis was confirmed through morphological changes and analysis of the B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein ratio, along with the activation of caspase-3, -8, and -9.

Main Results:

  • DPT significantly inhibited the viability of QBC939 and RBE cells in a dose- and time-dependent manner.
  • DPT treatment led to G2/M phase cell cycle arrest, accompanied by decreased Cyclin B and cyclin-dependent kinase 1 expression.
  • DPT induced apoptosis, evidenced by morphological changes, altered Bcl-2/Bax ratios, and activated caspase-3, -8, and -9.

Conclusions:

  • Deoxypodophyllotoxin (DPT) demonstrates significant anti-proliferative and cytotoxic effects against human cholangiocarcinoma cells.
  • DPT-induced cytotoxicity is mediated through cell cycle arrest at the G2/M phase and the induction of apoptosis via caspase activation.
  • DPT shows potential as a novel anticancer agent for the treatment of human cholangiocarcinoma.
Keywords:
G2/M arrestapoptosischolangiocarcinomadeoxypodophyllotoxinproliferation

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