Cytotoxic and cell cycle arrest properties\xa0of two steroidal alkaloids isolated from Holarrhena floribunda (G. Don) T. Durand & Schinz leaves

J A Badmus,M Meyer,A A Hussein,D C Hiss,O E Ekpo

doi:10.1186/s12906-019-2521-9

Abstract

BackgroundThe plant Holarrhena floribunda (H. floribunda; G. Don) is indigenous to sub-Saharan Africa and is traditionally used to treat several ailments. The present study was carried out to isolate and characterize bioactive compounds with anti-proliferative activity present in H. floribunda extracts.MethodsCompounds were isolated from H. floribunda using the bioassay-guided fractionation technique of repeated column chromatography and the step-wise application of the MTT reduction assay to assess antiproliferative bioactivity. The structures of the compounds were identified mainly using NMR. The effects of the isolated compounds on the viability, cell cycle and proliferation of human cancer cell lines (MCF-7, HeLa and HT-29) as well as the non-cancerous human fibroblast cell line (KMST-6) were investigated.ResultsBioassay-guided fractionation yielded two steroidal alkaloids: holamine (1) and funtumine (2). The MTT reduction assay shows that both compounds exhibited selective dose-dependent cytotoxicity against the cancer cell lines studied. The isolated compounds induced cell cycle arrest at the G0/G1 and G2/M phases in the cancer cell lines with significant reduction in DNA synthesis. The results obtained show that the cancer cells (MCF-7, HeLa and HT-29) used in this study were more sensitive to the isolated compounds compared to the noncancerous fibroblast cells (KMST-6).ConclusionThe ability of the isolated compounds to cause cell cycle arrest and reduce DNA synthesis raises hopes for their possible development and use as potent anticancer drugs. However, more mechanistic studies need to be done for complete validation of the efficacy of the two compounds.

Highlights

The nuclear magnetic resonance (NMR) spectral data of the two compounds and their structures are presented in Table 1 and Fig. 1 respectively
The cytotoxicity data showed that compound 1 induced significant cytotoxicity on HT-29 cancer cells compared with the other cancer cell lines with the lowest Half maximal inhibitory concentration (IC50) of 31.06 μM followed by MCF-7 (42.82 μM), HeLa (51.42 μM) and KMST-6
This study described the isolation of two steroidal alkaloids from the H. floribunda

Summary

Introduction

Plants are a reservoir of compounds with chemical diversity that provides leads for the discovery of new drugs against human diseases [1]. Folklore medicine as practiced worldwide demonstrates that plants are an important and reliable source of bioactive antitumour, antioxidant and antimicrobial compounds [2]. The medicinal constituents derived from plants are important as therapeutic agents, but could serve as templates for the synthesis of active drugs with desired therapeutic profiles [5]. This has opened new vistas for delineating the structural importance of bioactive components of plants. A typical example is camptothecin, which has been developed into different analogues (topotecan, irinotecan, belatecan and 9-aminocamptothecin) [6]

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