Morinda citrifolia Leaf Extract Suppressed Metastasised Cancer Progression via EGFR and MAPK Pathways

Swee-Ling Lim; Noordin M. Mustapha; Yong-Meng Goh; Heshu S. Rahman; Suhaila Mohamed

doi:10.1055/s-0043-107030

Planta Medica International Open, Table of Contents

CC BY-NC-ND 4.0 · Planta Medica International Open 2017; 4(01): e8-e16
DOI: 10.1055/s-0043-107030

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Morinda citrifolia Leaf Extract Suppressed Metastasised Cancer Progression via EGFR and MAPK Pathways

Authors

Swee-Ling Lim

¹UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
Noordin M. Mustapha

²Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
Yong-Meng Goh

²Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
Heshu S. Rahman

¹UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
Suhaila Mohamed

¹UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

Abstract

Morinda citrifolia leaf has anti-inflammatory and immune enhancing effects against lung cancer. The effects of the extract on metastasised lung and liver cancer tissues were compared to Erlotinib (an anticancer drug) for cancer aggression, proliferation, and angiogenesis. Forty Balb/c mice were induced to develop metastatic lung and liver tumours via xenograft subcutaneous injection of non-small cell lung cancer A549 cells (2×10⁷ cells/mouse) into their backs. The extract (150 and 300 mg/kg body weight) and Erlotinib (50 mg/kg body weight) were fed to the mice for 21 days, and the microstructure and mRNA expressions of the tumour tissues were analysed. The extract dose-dependently downregulated RAC-alpha serine/threonine-protein kinase, B cell leukaemia/lymphoma 2, mitogen-activated protein kinase kinase kinase 14, mitogen-activated protein kinase 1, and vascular endothelial growth factor alpha in these tissues. The scopoletin (coumarin) and epicatechin (flavonoid) standardised extract also mitigated the cancerous tissues microstructure changes, and suppressed the tissue remodeling enzyme (matrix metallopeptidase 9) and angiogenesis biomarkers (epidermal growth factor receptor and integrin). The 300 mg extract/kg body weight was more effective than the 50 mg Erlotinib/kg body weight in suppressing the lung and liver tumoor metastasis. The extract inhibited the cancer aggression by interfering with epidermal growth factor receptor and mitogen-activated protein kinase carcinogenesis pathways, and suppressing proliferation, tissue remodelling, and angiogenesis without any observable side effects at the given dose.

Key words

Morinda citrifolia - Rubiaceae - scopoletin - epicatechin - carcinogenesis - angiogenesis

Full Text

References

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