Bioactive Pentacyclic Triterpenes Trigger Multiple Signalling Pathways for Selective Apoptosis Leading to Anticancer Efficacy: Recent Updates and Future Perspectives.

Nowadays, discovering an effective and safe anticancer medication is one of the major challenges. Premature death due to the unidirectional toxicity of conventional therapy is common in cancer patients with poor health status. Plants have been used as medicine since prehistoric times, and extensive research on the anticancer properties of various bioactive phytomolecules is ongoing. Pentacyclic triterpenoids are secondary metabolites of plants with well-known cytotoxic and chemopreventive properties established in numerous cancer research studies. The lupane, oleanane, and ursane groups of these triterpenoids have been well-studied in recent decades for their potential antitumor activity. This review delves into the molecular machinery governing plant-derived triterpenes' anticancer efficacy. The highlighted mechanisms are antiproliferative activity, induction of apoptosis through regulation of BCL-2 and BH3 family proteins, modulation of the inflammatory pathway, interference with cell invagination and inhibition of metastasis. Lack of solubility in mostly used biological solvents is the major barrier to the therapeutic progress of these triterpenoids. This review also highlights some probable ways to mitigate this issue with the help of nanotechnology and the modification of their physical forms.

Banerjee J ，Samanta S ，Ahmed R ，Dash SK ... -  《-》

Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy.

Today cancer treatment is not only a question of eliminating cancer cells by induction of cell death. New therapeutic strategies also include targeting the tumour microenvironment, avoiding angiogenesis, modulating the immune response or the chronic inflammation that is often associated with cancer. Furthermore, the induction of redifferentiation of dedifferentiated cancer cells is an interesting aspect in developing new therapy strategies. Plants provide a broad spectrum of potential drug substances for cancer therapy with multifaceted effects and targets. Pentacyclic triterpenes are one group of promising secondary plant metabolites. This review summarizes the potential of triterpenes belonging to the lupane, oleanane or ursane group, to treat cancer by different modes of action. Since Pisha et al. reported in 1995 that betulinic acid is a highly promising anticancer drug after inducing apoptosis in melanoma cell lines in vitro and in vivo, experimental work focused on the apoptosis inducing mechanisms of betulinic acid and other triterpenes. The antitumour effects were subsequently confirmed in a series of cancer cell lines from other origins, for example breast, colon, lung and neuroblastoma. In addition, in the last decade many studies have shown further effects that justify the expectation that triterpenes are useful to treat cancer by several modes of action. Thus, triterpene acids are known mainly for their antiangiogenic effects as well as their differentiation inducing effects. In particular, lupane-type triterpenes, such as betulin, betulinic acid and lupeol, display anti-inflammatory activities which often accompany immune modulation. Triterpene acids as well as triterpene monoalcohols and diols also show an antioxidative potential. The pharmacological potential of triterpenes of the lupane, oleanane or ursane type for cancer treatment seems high; although up to now no clinical trial has been published using these triterpenes in cancer therapy. They provide a multitarget potential for coping with new cancer strategies. Whether this is an effective approach for cancer treatment has to be proven. Because various triterpenes are an increasingly promising group of plant metabolites, the utilisation of different plants as their sources is of interest. Parts of plants, for example birch bark, rosemary leaves, apple peel and mistletoe shoots are rich in triterpenes and provide different triterpene compositions.

Laszczyk MN 《-》

Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies.

Kaps A ，Gwiazdoń P ，Chodurek E 《MOLECULES》

Pentacyclic triterpenoids and their saponins with apoptosis-inducing activity.

Wang SR ，Fang WS 《-》

Novel targets of pentacyclic triterpenoids in Staphylococcus aureus: A systematic review.

Staphylococcus aureus is an important pathogen both in community-acquired and healthcare-associated infections, and has successfully evolved numerous strategies for resisting the action to practically all antibiotics. Resistance to methicillin is now widely described in the community setting (CMRSA), thus the development of new drugs or alternative therapies is urgently necessary. Plants and their secondary metabolites have been a major alternative source in providing structurally diverse bioactive compounds as potential therapeutic agents for the treatment of bacterial infections. One of the classes of natural secondary metabolites from plants with the most bioactive compounds are the triterpenoids, which comprises structurally diverse organic compounds. In nature, triterpenoids are often found as tetra- or penta-cyclic structures. This review highlights the anti-staphylococcal activities of pentacyclic triterpenoids, particularly α-amyrin (AM), betulinic acid (BA) and betulinaldehyde (BE). These compounds are based on a 30-carbon skeleton comprising five six-membered rings (ursanes and lanostanes) or four six-membered rings and one five-membered ring (lupanes and hopanes). Electronic databases such as ScienceDirect, PubMed and Scopus were used to search scientific contributions until March 2018, using relevant keywords. Literature focusing on the antimicrobial and antibiofilms of effects of pentacyclic triterpenoids on S. aureus were identified and summarized. Pentacyclic triterpenoids can be divided into three representative classes, namely ursane, lupane and oleananes. This class of compounds have been shown to exhibit analgesic, immunomodulatory, anti-inflammatory, anticancer, antioxidant, antifungal and antibacterial activities. In studies of the antimicrobial activities and targets of AM, BA and BE in sensitive and multidrug-resistant S. aureus, these compounds acted synergistically and have different targets from the conventional antibiotics. The inhibitory mechanisms of S. aureus in novel targets and pathways should stimulate further researches to develop AM, BA and BE as therapeutic agents for infections caused by S. aureus. Continued efforts to identify and exploit synergistic combinations by the three compounds and peptidoglycan inhibitors, are also necessary as alternative treatment options for S. aureus infections.

Chung PY 《-》