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Chlorophyllin abrogates canonical Wnt/β-catenin signaling and angiogenesis to inhibit the development of DMBA-induced hamster cheek pouch carcinomas

An Erratum to this article was published on 16 February 2013

Abstract

Background

Chlorophyllin, a water soluble semi-synthetic food-grade derivative is reported to exhibit a wide range of beneficial health effects. We investigated the effect of chlorophyllin supplementation on Wnt/β-catenin and vascular endothelial growth factor (VEGF) signaling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model.

Methods and results

Hamsters were divided into 4 groups. The right buccal pouches of group 1 and 2 hamsters were painted with 0.5 % DMBA for 14 weeks. Group 2 animals received in addition chlorophyllin (4 mg/kg bw) in the diet. Group 3 animals received chlorophyllin alone and group 4 animals served as control. mRNA and protein expression of components of Wnt, VEGF, and PI3K/Akt signaling pathways were analyzed by RT-PCR and Western blot analysis. Dietary chlorophyllin administration suppressed the development of HBP carcinomas by altering the expression of several components of the Wnt/β-catenin signaling pathway. This was associated with inhibition of angiogenesis as evidenced by decreased expression of the proangiogenic factors HIF-1α, VEGF, and VEGFR2. Chlorophyllin administration also downregulated the expression of histone deacetylases involved in epigenetic regulation of tumor angiogenesis.

Conclusion

Dietary chlorophyllin that abrogates Wnt/β-catenin and VEGF signaling by targeting a multitude of key signaling molecules is an attractive candidate for preventing tumor progression.

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Acknowledgements

We gratefully acknowledge the technical assistance of Mr. P. Thiyagarajan. This work was supported by a grant from the Department of Biotechnology, New Delhi, India under the 7th FP of the Indo-EU Joint Collaborative Project on ‘FUNCFOOD’ (BT/IN/EU/17/SN/2009).

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This research complies with the ethical guidelines of the Indian Council of Medical Research, and has been approved by the institutional ethical committee.

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Correspondence to Nagini Siddavaram.

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Siddavaram, N., Ramamurthi, V.P., Veeran, V. et al. Chlorophyllin abrogates canonical Wnt/β-catenin signaling and angiogenesis to inhibit the development of DMBA-induced hamster cheek pouch carcinomas. Cell Oncol. 35, 385–395 (2012). https://doi.org/10.1007/s13402-012-0099-z

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Keywords

  • Angiogenesis
  • Chlorophyllin
  • Hamster buccal pouch
  • PI3K
  • Wnt