Myrtucommulone-A Induces both Extrinsic and Intrinsic Apoptotic Pathways in Cancer Cells

Abstract

Myrtucommulone-A is the active compound derived from Myrtus communis. The molecular targets of myrtucommulone-A is widely unknown, which impedes its potential therapeutic use. In this study, we demonstrated the cytotoxicity of MC-A and its potential to induce apoptosis in cancer cells. Myrtucommulone-A was also found to be antiproliferative and strongly inhibited cancer cell migration. Eighty four apoptotic pathway genes were used to assess the effect of myrtucommulone-A on cancer cells. Myrtucommulone-A mediated an increase in apoptotic genes including Fas, FasL, Gadd45a, Tnf, Tnfsf12, Trp53, and caspase 4. The increase in myrtucommulone-A dose (25 μM versus 6.25 μM) also upregulated the expression of genes, which are involved mainly in apoptosis, regulation of apoptosis, role of mitochondria in apoptotic signaling, cytokine activity, and tumor necrosis factor signaling. Our data indicate that myrtucommulone-A could be utilized as a potential therapeutic compound with its molecular targets in apoptotic pathways.

Structures and Bioactive Properties of Myrtucommulones and Related Acylphloroglucinols from Myrtaceae

“…The compound mediated an increased expression of several apoptotic genes, such as Fas, FasL, Gadd45a, Tnf, Tnfsf12, Trp53, and caspase-4. Moreover, the results of a wound healing experiment showed that it is also able to inhibit cancer cell migration [111]. All these effects were enhanced when treatment was operated in combination with epirubicin or cisplatin, evidencing a synergistic effect that could be exploited for setting more effective therapeutic schemes [112].…”

Catalytic asymmetric total syntheses of myrtucommuacetalone, myrtucommuacetalone B, and callistrilones A, C, D and E

“…These natural products have become attractive targets for chemists because of their complex structural features, and some PPPs have been reported to exhibit biological activities. 1 , 2 For example, myrtucommulone A ( 1 ), which was first isolated in 1974, is highly active against Gram-positive bacteria and cancer cells. 1a , b Myrtucommuacetalone ( 2 ) exhibits inhibitory activity towards the production of nitric oxide (NO˙), as well as pronounced antiproliferative activity against T-cells.…”

Mitochondrial Chaperonin HSP60 Is the Apoptosis-Related Target for Myrtucommulone

“…Myrtucommulone A (MC, Figure 2A) is a non-prenylated acylphloroglucinol contained in myrtle (Myrtus communis, myrtaceae) displaying multiple bioactivities such as antibacterial (Rotstein et al, 1974;Appendino et al, 2002), antioxidant (Rosa et al, 2003), anti-inflammatory (Feisst et al, 2005;Rossi et al, 2009), and anti-tumoral properties (Grandjenette et al, 2015;Izgi et al, 2015;Tretiakova et al, 2008). The microsomal prostaglandin E 2 (PGE 2 ) synthase 1 (mPGES-1) and 5-lipoxygenase (5-LO) were identified as targets of MC, rationalizing the suppression of PGE 2 and leukotriene biosynthesis as anti-inflammatory features (Feisst et al, 2005;Koeberle et al, 2009).…”