HLBT-100: a highly potent anti-cancer flavanone from Tillandsia recurvata (L.) L.

Abstract

BackgroundThe incidence and mortalities from cancers remain on the rise worldwide. Despite significant efforts to discover and develop novel anticancer agents, many cancers remain in the unmet need category. As such, efforts to discover and develop new and more effective and less toxic agents against cancer remain a top global priority. Our drug discovery approach is natural products based with a focus on plants. Tillandsia recurvata (L.) L. is one of the plants selected by our research team for further studies based on previous bioactivity findings on the anticancer activity of this plant.MethodsThe plant biomass was extracted using supercritical fluid extraction technology with CO2 as the mobile phase. Bioactivity guided isolation was achieved by use of chromatographic technics combined with anti-proliferative assays to determine the active fraction and subsequently the pure compound. Following in house screening, the identified molecule was submitted to the US National Cancer Institute for screening on the NCI60 cell line panel using standard protocols. Effect of HLBT-100 on apoptosis, caspase 3/7, cell cycle and DNA fragmentation were assessed using standard protocols. Antiangiogenic activity was carried out using the ex vivo rat aortic ring assay.ResultsA flavonoid of the flavanone class was isolated from T. recurvata (L.) L. with potent anticancer activity. The molecule was code named as HLBT-100 (also referred to as HLBT-001). The compound inhibited brain cancer (U87 MG), breast cancer (MDA-MB231), leukemia (MV4-11), melanoma (A375), and neuroblastoma (IMR-32) with IC50 concentrations of 0.054, 0.030, 0.024, 0.003 and 0.05 µM, respectively. The molecule also exhibited broad anticancer activity in the NCI60 panel inhibiting especially hematological, colon, CNS, melanoma, ovarian, breast and prostate cancers. Twenty-three of the NCI60 cell lines were inhibited with GI50 values <0.100 µM. In terms of potential mechanisms of action, the molecule demonstrated effect on the cell cycle as evidenced by the accumulation of cells with <G1 DNA content, activation of caspase 3/7, DNA fragmentation and culminating in apoptotic cell death. HLBT-100 also demonstrated antiangiogenic potential by inhibiting capillary sprout and tube formation in a dose dependent manner in the ex vivo rat aortic ring.ConclusionThis paper describes for the first time the anticancer activity of HLBT-100 isolated from T. recurvate (L.) L. The broad and selective anticancer activity of HLBT-100 as evidenced by its potent activity against IMR-32, CNS cancer cell line while not active against neuro-2a, a normal CNS cell line. The activity demonstrated by HLBT-100 in these studies makes the molecule a potential candidate for further development targeting especially those cancers that remain in the unmet need category such as glioblastoma multiforme and acute myeloid leukemia in addition to other cancers.

In vitro assays and techniques utilized in anticancer drug discovery

“…WST assay has also been used frequently as a cell viability assay. Lowe, Toyang, Watson, Ayeah, and Bryant () have utilized WST assay to assess cytotoxic effects of a flavonoid (HLBT‐100) in brain (U87 MG), breast (MDA‐MB‐231), melanoma (A375), leukemia (MV4‐11) and prostate (PC‐3) cancer cell lines. An in vitro study conducted by Chen et al () demonstrated cytotoxic effects of hinokitiol in breast cancer stem/progenitor cells using the WST assay.…”

“…WST assay has also been used frequently as a cell viability assay. Lowe, Toyang, Watson, Ayeah, and Bryant (2017) have utilized WST assay to assess cytotoxic effects of a flavonoid (HLBT-100) in brain (U87 MG), breast (MDA-MB-231), melanoma (A375), leukemia (MV4-11) and prostate (PC-3) cancer cell…”

Characterization and Distribution of Flavonoids from Flowers in Different Horticultural Types of Begonia

“…7 On the other hand, these phenolic compounds have showed wide range of pharmacological activities including antioxidant, 8 anti-inflammatory, 9 antimicrobial, 10,11 antihemorragic activities 12 and anticancer activity. 13 In recent years, the study of the flavonoids took a great place in research studies due to the improvement of the extractive techniques and the progress of the methods of structural analysis. Hence, the present study intended to identify the flavonoids isolated from flowers and their distribution in different horticultural types of Begonia.…”

Anti-virulence activities of some Tillandsia species (Bromeliaceae)

“…The Bromeliaceae family is composed of 58 genera and 3,408 species native to America distributed from Argentina to the southern United States (Benzing 2000, Luther 2014). Some species have important pharmacological activities, such as anthelmintic (Stepek et al 2005), antinociceptive (de Lima-Saraiva et al 2014), gastroprotective (Machado et al 2013), photoprotective (de Oliveira-Júnior et al 2017), anticancer (Lowe et al 2017), hypoglycemic (Witherup et al 1995) and antibacterial (Faller et al 2017) activity.…”