Antitumor effect of acanthoic acid against primary effusion lymphoma via inhibition of c‐FLIP

Abstract

Acanthoic acid (AA) is an active substance that is extracted from Croton oblongifolius Roxb., a traditional plant in Thailand. The antiinflammatory effect of AA on NF-κB pathway has been exclusively reported, however, its anticancer effect is still lacking. PEL is a B cell lymphoma that is mostly found in HIV patients. The prognosis and progression of PEL patients are terribly poor with a median survival time less than 6 months, so the new effective treatment is urgently needed. In this study, we found that AA effectively inhibited PEL cell proliferation with IC50s at 120-130 μM in well-representative cells, while the IC50s of AA in PBMC were higher (>200 μM). AA increased percentages of Annexin V/PI positive cells, whereas adding of caspase inhibitor (Q-VD-OPh) prevented AA-induced cell death. The antiapoptotic protein, c-FLIP, was downregulated by AA which leading to the activation of caspase-8 and -3. Combination of AA and TRAIL dramatically enhanced apoptotic cell death. In PEL xenograft model, AA at the dose of 250 mg/kg effectively

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“…Most terpenoids are isolated from medicinal plants that belong to the following plant groups: Oleaceae, Rutaceae, Labiatae, Acanthaceae, Compositae, Taxaceae, Pinaceae, Lauraceae, Araliaceae, Celastraceae, etc. Terpenoids are classified according to the number of isoprene (2-methylbuta-1, 3-diene) units into monoterpenoids (C 10 ), Menthol Peppermint oil (Mentha piperita) [17] Myrcene bay laurel oil (Laurus nobilis) and Verbena oil (Lippia citriodora) [18] Perillyl alcohol [19] Eucalyptol (1.8-cineole) Eucalyptus leaf oil (Eucalyptus globules), rosemary (Rosmarinus officinalis) [20] Sesquiterpenoids Artemisinin and its derivatives Sweet wormwood (Artemisia annua) [21] Costunolide Aucklandia lappa [22,23] Diterpenoids Acanthoic acid Acanthopanax koreanum Nakai, Croton oblongifolius Roxb [24,25] Oridonin Rabdosia rubescens [26] Tanshinone IIA Salvia miltiorrhiza Bge [27] Taxol (Paclitaxel) Taxus brevifolia [28] Triptolide Tripterygium wilfordii [29,30] Kaurenoic acid Annona senegalensis (Annonaceae) [31] Triterpenoids Celastrol Tripterygium wilfordii [29] Withaferin A Withania somnifera [32] Ursolic acid Rosmarinus officinalis (rosemary), Calluna vulgaris and Eugenia jambolana, Salvia officinalis, and Eriobotrya japonica [33] Tetraterpenoids Lycopene Tomatoes (Lycopersicon esculentum), pink guavas, apricots, water melon, and pink grapefruits [34,35] Lutein Spinach, kale, carrot, corn, and egg yolk [36,37] β-carotene Carrot [38] sesquiterpenoids (C 15 ), diterpenoids (C 20 ), triterpenoids (C 30 ), tetraterpenoids (C 40 ), and polyterpenoids (C > 40) [Table 1]. They possess vast medicinal importance that includes: antitumor, antibacterial, antimalarial, anti-inflammatory, antiviral, anticancer, immunomodulatory, anti-aging, antioxidant, anti-depressants, antifungal, and antidiabetic.…”