Short Lecture "Plectranthus diterpenes: A promising therapy for glioblastoma treatment"

Plectranthus genus (Lamiaceae) is known to be rich in bioactive diterpenes abietane-type royleanones, such as 7α-acetoxy-6β-hydroxyroyleanone (Roy), 7β,6β-dihydroxyroyleanone (DiRoy), Parviflorone D (ParvD) and 6,7- dehydroroyleanone (DeRoy). Roy and DiRoy are frequently found in the extracts of the species P. hadiensis, ParvD in P. ecklonii and DeRoy in P. aliciae. These compounds can be considered as lead molecules to search new treatments against glioblastoma (GB) regarding their proven pro-apoptotic nature in H7PX cells. The bioguided isolation from P. hadiensis stem acetonic extract resulted in the obtention of Roy and DiRoy, which were the major compounds according to the HPLC-DAD profile of the extract. Among these compounds, Roy showed low IC₅₀ values (range of 6.21-56.91 µg/mL at 24 h) among the different glioblastoma cell lines (U87, A172, U118, U373 and H4) in the Alamar blue assay. The uptake of the probe derivative BODIPY-Roy by GB cells increased intracellular fluorescence, supporting the strong antiproliferative effects of Roy. Also, theParvD diterpene showed a mechanism by which it exerts pronounced inhibitory effects (with substantially lower doses than that of Temozolomide, the current first-line treatment) involving intrinsic apoptosis and G2/M cell cycle arrest. Currently, the study of the extraction optimisation of these bioactive compounds, their mechanism of action, their in-vivo activity and the synthesis of some derivatives is on-going to explore the huge potential of these diterpenoids and their derivatives to be used as a helpful source of new drugs to improve GB treatment and to overcome resistances.

 

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Conflict of Interest

The authors declare no conflict of interest.

Publication History

Article published online:
16 November 2023