Prostratin: An Overview

Abstract

Terpenoid class of molecules possesses a diverse therapeutic properties and potentials owing to their specific structural features. Prostratin and its derivatives are exemplified in this context to exhibit a variety of biological activities. In this review we discuss in detail the role of prostratin as potential therapeutic and underlying molecular mechanisms by which it accomplishes these activities. Prostratin [13-O-acetyl-12-deoxyphorbol] is a phorbol ester that was first isolated from Strathmore weed Pimelea prostrate, a small endemic New Zealand shrub, and characterized by Hecker in 1976. Structurally, prostratin contains four rings designated as A, B, C and D. Ring A is trans linked to the 7-membered ring B while Ring C is a 6 membered and is cis linked to the cyclopentane ring D. Chemical synthesis of this compound initiated with acidic hydrolysis of phorbol, a tigliane diterpene isolated from croton oil. Prostratin-containing extracts have been used by the Samoan healers to treat individuals with certain medical conditions such as jaundice. Importantly, these treatments are not associated with any significant side effect. Prostratin inhibits HIV-1 infections by down regulating HIV-1 cellular receptors through the activation of protein kinase C (PKC) pathway and reduces the HIV-1 latency. Unlike other phorbol esters that induce carcinogenesis by activating PKC, prostratin does not induce tumors rather has shown tumor suppressing activity. Its ability to induce lytic gene expression supports a role for phorbol-ester regulated signaling pathways in Kaposi's sarcoma associated herpes-virus reactivation.

Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques

“…After 400 days of viral suppression, defined as fewer than 30 SIV copies/ml in plasma measured by qPCR and confirmed by digital droplet PCR, one animal (Mn0) was maintained as procedural control and two macaques (Mn1 and Mn2) were treated with latency reversing agents. Because no Food and Drug Administration-approved compound has been successfully used to reactivate HIV-1 latent reservoirs in virally suppressed humans or nonhuman primates [28–31], we used the novel PKC activator ingenol-B, which had been previously evaluated in vitro and was efficient in activating HIV-1 long-term repeats in reporter cell lines [32–34]. Before testing the compound in our SIV-macaque model, however, we evaluated whether ingenol-B activates viral genomes in ex-vivo primary cells.…”

Phorbol esters dPPA/dPA promote furin expression involving transcription factor CEBPβ in neuronal cells

“…10 μM of these drugs did not interfere with the viability in both SH-SY5Y and HEK293 cells (Figure 1B and 1C ). Since PMA and PDBu may induce carcinogenesis [ 19 ], we then selected dPA and dPPA that have been proved as antineoplastic agents [ 20 , 21 ], for further study. We first assessed the effect of dPA or dPPA on furin protein expression in SH-SY5Y cells.…”

“…As described above, PMA and dPPA may differ in functions. The former is carcinogenic while the latter is antineoplastic [ 19 – 21 ]. Another possibility is that P1 promoter may be activated in a tissue- and cell differentiation-dependent manner [ 26 ].…”

12-Deoxyphorbol Esters Induce Growth Arrest and Apoptosis in Human Lung Cancer A549 Cells Via Activation of PKC-δ/PKD/ERK Signaling Pathway

“…Prostratin, a 12-deoxyphorbol ester, has been extensively studied for its potential use in human immunodeficiency virus (HIV) adjuvant therapy, because it is able to reduce HIV latency by activating PKC [ 27 , 28 ]. Recently, prostratin is also emerging as a promising anticancer agent.…”