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Journal of Molecular Medicine

, Volume 81, Issue 10, pp 664–673 | Cite as

Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients: assessment of the most important laboratory indexes of cachexia and oxidative stress

  • Giovanni Mantovani
  • Antonio Macciò
  • Clelia Madeddu
  • Loredana Mura
  • Giulia Gramignano
  • Maria Rita Lusso
  • Elena Massa
  • Miria Mocci
  • Roberto Serpe
Original Article

Abstract

This study assessed in a wide population of advanced cancer patients the biological parameters relevant to cancer cachexia, such as serum levels of proinflammatory cytokines (IL-1β, IL-6, TNFα), IL-2, acute-phase proteins (C-reactive protein and fibrinogen), leptin, and relevant to oxidative stress (OS), such as ROS, body antioxidant enzymes GPx and SOD. We also studied the ability of effective antioxidant agents α-lipoic acid (ALA), N-acetyl cysteine (NAC), and amifostine (AMI) added into culture to induce lymphocyte progression through the cell cycle, namely to enter into S phase. Additionally, we assessed the most significant clinical indexes of nutritional status such as body mass index and disease progression such as stage and ECOG-PS in the same cancer patient population. Cell cycle analysis of cultured unstimulated or PHA-stimulated PBMCs isolated from 120 cancer patients and 60 controls, with or without ALA, NAC, or AMI, was studied. The biological parameters relevant to cancer cachexia and OS were also studied. The addition of antioxidants ALA, NAC and AMI, enhanced significantly the progression through the cell cycle, namely from G0/G1 to S phase, of PBMCs isolated from cancer patients (+132%, +150% and +141%, respectively). The percentage of PHA-stimulated PBMCs of cancer patients entering S phase, which was significantly lower than that of controls, increased significantly to more than physiological level after coculture with antioxidants. ROS levels were significantly higher and GPx and SOD activities significantly lower in cancer patients than controls. Serum levels of IL-1 β, IL-6, and TNFα were significantly higher and serum levels of IL-2 and leptin significantly lower in cancer patients than controls. Serum levels of C-reactive protein and fibrinogen were significantly higher in cancer patients than controls. A significant correlation was found in laboratory parameters only between serum levels of leptin and body mass index. Patients with advanced cancer thus exhibit both a high-grade OS and a chronic inflammatory condition. Antioxidant agents ALA, NAC, and AMI enhanced significantly the PBMCs progression through the cell cycle, thus providing evidence of their potential role in the functional restoration of the immune system in advanced cancer patients. Our data warrant further investigation with adequate clinical trials.

Keywords

Antioxidant agents Cell cycle progression Proinflammatory cytokines Oxidative stress Advanced cancer patients 

Abbreviations

ALA

α-Lipoic acid

AMI

Amifostine

BMI

Body mass index

CRP

C-reactive protein

ECOG-PS

Performance status as assessed by the Eastern Cooperative Oncology Group

GPx

Glutathione peroxidase

IL

Interleukin

NAC

N-Acetyl cysteine

OS

Oxidative stress

PBMC

Peripheral blood mononuclear cell

PHA

Phytohemagglutinin

ROS

Reactive oxygen species

SOD

Superoxide dismutase

TCR

T cell receptor

TNF

Tumor necrosis factor

Notes

Acknowledgements

This research was supported by a grant from Ministry of University, Scientific Research and Technology, Rome, Italy (National Research Project No. 9906041835). We thank Dr. Roberto Serpe for his excellent technical assistance and Ms. Anna Rita Succa for her helpful linguistic assistance.

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Giovanni Mantovani
    • 1
  • Antonio Macciò
    • 1
  • Clelia Madeddu
    • 1
  • Loredana Mura
    • 1
  • Giulia Gramignano
    • 1
  • Maria Rita Lusso
    • 1
  • Elena Massa
    • 1
  • Miria Mocci
    • 1
  • Roberto Serpe
    • 1
  1. 1.Department of Medical Oncology, Policlinico UniversitarioUniversity of CagliariMonserratoItaly

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