Diterpenoids from Plectranthus spp. as Potential Chemotherapeutic Agents via Apoptosis.

Tomasz Śliwiński,Michał Bijak,Tomasz Kowalczyk,Przemysław Sitarek,Patrícia Rijo,Ewa Skała,Ewelina Synowiec,Vera M S Isca

doi:10.3390/ph13060123

Abstract

Plectranthus spp. is widely known for its medicinal properties and bioactive metabolites. The cytotoxic and genotoxic properties of the four known abietane diterpenoids: 7α-Acetoxy-6β-hydroxyroyleanone (Roy), 6,7-dehydroroyleanone (Deroy), 7β,6β-dihydroxyroyleanone6 (Diroy), and Parvifloron D (Parv), isolated from P. madagascariensis (Roy, DeRoy, and Diroy) and P. ecklonii (Parv) were evaluated. The tested compounds showed cytotoxic effects against the human leukemia cell line CCRF-CEM and the lung adenocarcinoma cell line A549. All tested compounds induced apoptosis by altering the level of pro- and anti-apoptotic genes. The results show that from the tested diterpenoids, Roy and Parv demonstrated the strongest activity in both human cancer cell lines, changing the permeability mitochondrial membrane potential and reactive oxygen species (ROS) levels, and possibly inducing mtDNA or nDNA damage. In conclusion, the abietane diterpenoids tested may be used in the future as potential natural chemotherapeutic agents

Highlights

Cancer is one of the most common causes of death worldwide [1,2]
The present study found an increase in lesion rate in the ND5 region: 19.51 lesions per 10 kb DNA in A549 cells treated with Diroy for 24 h and 7.90 and 13.73 lesions per 10 kb DNA in CCRFCEM cells treated with Deroy and Parvifloron D (Parv) D for 24 h (Figure 9), respectively
Our results demonstrate that all tested abietane diterpenoids Roy, Deroy, Diroy, and Parv showed cytotoxic activity in the tested range of concentrations (0–100 μg/mL) in the human leukemia cell line and lung adenocarcinoma

Summary

Introduction

Cancer is one of the most common causes of death worldwide [1,2]. The need for new and effective cytotoxic agents promotes continuous research on natural products. Many isolated plant compounds have been found to offer potential as treatments and may serve as alternatives to chemotherapy, which is associated with high costs and serious side effects [3,4,5,6]. These compounds might serve as novel drugs for use in combination therapy in various types of cancer [7]. Diterpenes with an abietane skeleton attract special scientific interest as these are the most diverse type of diterpenoids isolated from the mentioned genus Alongside this characteristic, many abietane diterpenoids possess cytotoxic properties.

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Conclusion