Anti-inflammatory and antiproliferative activity of Helichrysum odoratissimum sweet. Against lung cancer

Tenille Esmear, Danielle Twilley, Velaphi Clement Thipe, Kattesh V. Katti, Vusani Mandiwana, Michel Lonji Kalombo, Suprakas Sinha Ray, Rirhandzu Rikhotso-Mbungela, Venugopal Reddy Bovilla, Subba Rao Madhunapantula, Lenka Langhanshova, Catarina Roma-Rodrigues, Alexandra R. Fernandes, Pedro Baptista, Silvestre Hlati, Judey Pretorius, Namrita Lall

Research output: Contribution to journalArticlepeer-review


Lung cancer remains the top killing cancer worldwide despite advances in treatment. Seven ethanolic plant extracts were selected and evaluated for their antiproliferative activity against the two main types of lung cancers: non-small cell (A549) and small cell lung cancer cells (SHP-77). An ethanolic extract of Helichrysum odoratissimum Sweet (HO) showed significant antiproliferative activity against lung cancer, with a fifty percent inhibitory concentration (IC50) of 83.43 ± 1.60 µg/mL (A549), 49.46 ± 0.48 µg/mL (SHP-77) and 50.71 ± 2.27 µg/mL, against normal lung epithelial cells (MRC-5), resulting in a selectivity index (SI) value of 0.61 on A549 cells and 1.03 on SHP-77 cells, which was compared to the positive drug control, actinomycin D where the SI values were found to be 2 and 0.25 against A549 and SHP-77 cells, respectively. Against murine macrophages (RAW 264.7) and hepatocytes (HepG2), the HO ethanolic extract showed IC50 values of 60.15 ± 1.98 µg/mL and 23.61 ± 1.06 µg/mL, respectively. Microscopy showed that the HO ethanolic extract induced apoptosis in the A549 and HepG2 cells at 50 µg/mL and 300 µg/mL, respectively. The HO ethanolic extract, furthermore, inhibited the pro-inflammatory enzymes, cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) with IC50 values of 7.94 ± 3.84 µg/mL and 2.08 ± 1.35 µg/mL, respectively, whereas the positive controls Ibuprofen (COX-2) and Zileuton (5-LOX) showed IC50 values of 0.85 ± 0.14 µg/mL and 0.06 ± 0.05 µg/mL, respectively. The activity of NAD(P)H quinone oxidoreductase-1 (NQO1), which is a direct target of nuclear factor erythroid-2-related factor-2 (NRF2), was significantly inhibited in the A549 cells by the HO ethanolic extract (at 125 µg/mL) when compared to the positive control, brusatol (at 500 nM). Using the ex ovo yolk sac membrane (YSM) assay, the HO ethanolic extract (at 18.5 µg/egg) showed a 31.65 ± 12.80% inhibition of blood vessel formation. This is the first report of the noteworthy antiproliferative activity of the HO ethanolic extract on lung cancer cells including its potential to target several enzymes associated with inflammation and therefore, should be considered for further analysis.
Original languageEnglish
Pages (from-to)525-538
Number of pages14
JournalSouth African Journal of Botany
Publication statusPublished - Mar 2024


  • 5-LOX
  • A549 lung cancer cells
  • Anti-inflammatory
  • COX-2
  • Gold nanoparticles
  • Helichrysum odoratissimum sweet.
  • In vivo angiogenesis
  • Microscopy
  • NQO1
  • Yolk sac membrane assay


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