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Updated: Nov 16, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Enhancing the chemosensitivity of HepG2 cells towards cisplatin by organoselenium pseudopeptides
Saad Shaaban1, Sameh M Shabana2, Yasair S Al-Faiyz3
1Department of Chemistry, College of Science, King Faisal University, P.O. Box 380, Al-Ahsa 31982, Saudi Arabia; Organic Chemistry Division, Department of Chemistry, Faculty of Science, Mansoura University, Egypt.
Abstract:
Despite all recent advances in the treatment of hepatocellular carcinoma (HCC), chemotherapy resistance still represents a major challenge in its successful clinical management. Chemo-sensitization offers an attractive strategy to counter drug resistance. Herein we report the identification of novel organoselenium-based pseudopeptides as promising highly effective chemo-sensitizers in treating HCC with cisplatin. A series of functionalized pseudopeptide- (5-9 and 17-19), peptidomimetic- (10-12 and 20-23), and tetrazole-based (13-16 and 24-27) organoselenium compounds were synthesized via isonitrile-based multicomponent reactions from two novel selenium-containing isocyanides. All compounds were evaluated for their cytotoxicity against HepG2 and the non-cytotoxic doses were used to restor the sensitivity of the cells to cisplatin. New organoselenium compounds (7, 9, 15, or 23) led to an effective chemo-sensitization of HepG2 cells towards cisplatin (up-to 27-fold). Cell cycle studies indicate that the most potent peptidomimetic diselenide 23 arrested cells at the S phase and induced apoptosis via ROS modulation.
Insights
Novel organoselenium compounds show promise in overcoming chemotherapy resistance in hepatocellular carcinoma (HCC). These agents effectively resensitize cancer cells to cisplatin, offering a new strategy for HCC treatment.
Area of Science:
- Medicinal Chemistry
- Oncology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) treatment faces challenges due to chemotherapy resistance.
- Chemo-sensitization is a key strategy to enhance the efficacy of existing cancer therapies.
Purpose of the Study:
- To identify novel organoselenium compounds as chemo-sensitizers for hepatocellular carcinoma (HCC).
- To evaluate the efficacy of these compounds in combination with cisplatin against HCC cells.
Main Methods:
- Synthesis of organoselenium compounds including pseudopeptides, peptidomimetics, and tetrazoles via isonitrile-based multicomponent reactions.
- Evaluation of cytotoxicity against HepG2 cells and assessment of chemo-sensitization effects with cisplatin.
- Cell cycle analysis and reactive oxygen species (ROS) modulation studies for potent compounds.
Main Results:
- Several organoselenium compounds demonstrated significant chemo-sensitization of HepG2 cells to cisplatin (up to 27-fold increase in sensitivity).
- Compound 23, a peptidomimetic diselenide, was identified as particularly potent.
- Compound 23 induced S-phase arrest and apoptosis, modulated by ROS.
Conclusions:
- Novel organoselenium-based pseudopeptides and peptidomimetics are effective chemo-sensitizers for HCC.
- Compound 23 represents a promising candidate for enhancing cisplatin efficacy in HCC treatment via cell cycle arrest and apoptosis induction.
