Inhibitory effect of mandarin juice rich in beta-cryptoxanthin and hesperidin on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary tumorigenesis in mice

Cancer Lett. 2001 Dec 28;174(2):141-50. doi: 10.1016/s0304-3835(01)00713-3.


Previously we reported that a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ), MJ2 and MJ5, especially MJ5, effectively suppressed chemically-induced rat colon carcinogenesis (Int. J. Cancer 88 (2000) 146). MJ2 and MJ5 prepared from MJ have higher amounts of beta-cryptoxanthin and hesperidin than MJ, suggesting that principle chemopreventive factors in MJs may be beta-cryptoxanthin and hesperidin. Present study was conducted to test whether these MJs could modify carcinogenesis in other organ, lung initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in male A/J mice. Mice were given an intraperitoneal injection of NNK (10 micromol in saline/mouse) to induce pulmonary neoplasms. They also received MJ, MJ2 or MJ5 as a drinking water at night for 21 weeks, starting 1 week after the NNK injection. Treatments with MJ, MJ2, and MJ5 reduced the incidence of lung tumors and the inhibition by MJ5 (29% reduction) was statistically significant (P<0.05). MJs treatment lowered the multiplicity of lung neoplasms without statistical significance. Immunohistochemically, MJs, especially MJ5, reduced proliferating cell nuclear antigen (PCNA)-positive index in the lung tumors without affecting PCNA index in hyperplastic alveolar cell lesions. These findings might suggest that MJ5, which contain 3.9 mg beta-cryptoxanthin and 100 mg hesperidin in 100 g sample), has chemopreventive ability against NNK-induced mouse lung tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Beverages
  • Carcinogens / toxicity*
  • Citrus
  • Cryptoxanthins
  • Hesperidin / pharmacology*
  • Immunoenzyme Techniques
  • Incidence
  • Injections, Intraperitoneal
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Male
  • Mice
  • Mice, Inbred A
  • Nitrosamines / toxicity*
  • Nucleolus Organizer Region / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Xanthophylls
  • beta Carotene / analogs & derivatives*
  • beta Carotene / pharmacology*


  • Anticarcinogenic Agents
  • Carcinogens
  • Cryptoxanthins
  • Nitrosamines
  • Proliferating Cell Nuclear Antigen
  • Xanthophylls
  • beta Carotene
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • Hesperidin