Anti-angiogenesis as a possible mechanism of action for anti-tumor (potential anti-cancer) activity of Crinum asiaticum leaf methanol extract

Sa’adiah Mohd. Yusoff  ^a*, Mohd Zaini Asmawi ^a, Amin Malik Shah Abdul Majid ^{a, b}, Mohamed Khadeer A. Basheer ^c, Shazmin  Kithur Mohamed ^a, Muhammad Asif ^a, Seyedeh Fatemeh Jafari ^a, Hussein Mahfoudh Baharetha ^{a, d}

Crinum asiaticum is used traditionally to treat inflammations and tumours. The aim of this work is to ascertain the scientific viability of its use in traditional medicine as an anti-tumour (potential anti-cancer) agent.

Abstract

Most chemotherapeutic agents can destroy tumours and retard cancer growth, but may damage normal cells and tissues as well. Thus, new anti-cancer drugs derived from natural products are expected to play an important role in the development of more effective and safer strategies to inhibit the progress of cancer, without inducing cell lethality in the healthy surrounding tissues. Crinum asiaticum is used traditionally to treat inflammations and tumours. The aim of this work is to ascertain the scientific viability of its use in traditional medicine as an anti-tumour (potential anti-cancer) agent. Due to its anti-inflammatory properties, it is hypothesised that the anti-tumour activity may be due to anti-angiogenic activity. Thus, in the present study, an attempt has been made to study the anti-angiogenic activity of the Crinum asiaticum leaf methanol extract (CALME) of the Malaysian species. Rat aortic ring assay results showed that CALME prevented new blood vessel formation from the aortic ring explants, with IC50 11.58 µg/ml. The effect of CALME on EAhy 926 cell proliferation (inhibition) had also been investigated, and the MTT results showed that CALME induces cytotoxic effects in EAhy 926 cells, since the IC50 value was found to be 12.18 μg/ml (active cytotoxicity). CALME inhibited endothelial cell migration, at a dose of approximately 12 μg/ml. This dose is similar to the dose at which cytotoxicity is observed in cell. CALME also inhibited the release of the proangiogenic cytokine, VEGF, but not significantly. GC-MS data confirmed the presence of lycorine in CALME. In conclusion, the present work supports the traditional use and previously related works on the plant, which confirm that CALME exhibits anti-angiogenic (potential anti-cancer) activity. However, the anti-angiogenic effect demonstrated by CALME is due to the cytotoxic nature of the extract, and less related to inhibition of one or more of angiogenesis process steps.

Keywords: anti-tumour; anti-angiogenic; Crinum asiaticum; aortic ring assay; EAhy 926 cell proliferation inhibition; cytotoxic; cell migration; VEGF; GC-MS; lycorine.

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