Cytotoxicity of Plumbagin, Rapanone and 12 other naturally occurring Quinones from Kenyan Flora towards human carcinoma cells

Our plain-English summary of Cytotoxicity of Plumbagin, Rapanone and 12 other naturally occurring Quinones from Kenyan Flora towards human carcinoma cells, by V. Kuete, L.K. Omosa, V.R. Tala, et al (BMC Pharmacology & Toxicology, 2016).

The study

• Authors: V. Kuete, L.K. Omosa, V.R. Tala, J.O. Midiwo, A.T. Mbaveng, S. Swaleh, O. Karaosmanoğlu, H. Sivas
• Journal: BMC Pharmacology & Toxicology
• Published: 2016;17(1):60
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Cancer is a major public health concern globally and chemotherapy remains the principal mode of the treatment of various malignant diseases.

Methods: This study was designed to investigate the cytotoxicity of 14 naturally occurring quinones including; 3 anthraquinones, 1 naphthoquinone and 10 benzoquinones against 6 human carcinoma cell lines and normal CRL2120 fibroblasts. The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspases activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) were measured by spectrophotometry.

Results: Anthraquinone: emodin (2), naphthoquinone: plumbagin (4), and benzoquinones: rapanone (9), 2,5-dihydroxy-3-pentadecyl-2,5-cyclohexadiene-1,4-dione (10), 5-O-methylembelin (11), 1,2,4,5-tetraacetate-3-methyl-6-(14-nonadecenyl)-cyclohexadi-2,5-diene (13), as well as doxorubicin displayed interesting activities with IC50 values below 100 μM in the six tested cancer cell lines. The IC50 values ranged from 37.57 μM (towards breast adenocarcinoma MCF-7 cells) to 99.31 μM (towards small cell lung cancer A549 cells) for 2, from 0.06 μM (MCF-7 cells) to 1.14 μM (A549 cells) for 4, from 2.27 μM (mesothelioma SPC212 cells) to 46.62 μM (colorectal adenocarcinoma DLD-1 cells) for 9, from 8.39 μM (SPC212 cells) to 48.35 μM (hepatocarinoma HepG2 cells) for 10, from 22.57 μM (MCF-7 cells) to 61.28 μM (HepG2 cells) for 11, from 9.25 μM (MCF-7 cells) to 47.53 μM (A549 cells) for 13, and from 0.07 μM (SPC212 cells) to 1.01 μM (A549 cells) for doxorubicin. Compounds 4 and 9 induced apoptosis in MCF-7 cells mediated by increased ROS production and MMP loss, respectively.

Conclusion: The tested natural products and mostly 2, 4, 9, 10, 11 and 13 are potential cytotoxic compounds that deserve more investigations towards developing novel antiproliferative drugs against human carcinoma.

In plain English

This study tested cells in dishes; it did not involve people or asbestos. The authors tested 14 plant-derived quinone compounds on six human cancer cell lines, including SPC212 mesothelioma cells, and on normal skin cells, comparing them with the drug doxorubicin. Six compounds and doxorubicin had IC50 values (the concentration that inhibits growth by half) below 100 μM in every cancer line. Compounds 3, 5 and 12 were not active against the cancer lines (IC50 above 120 μM), though compound 5 harmed the normal cells (IC50 95.51 μM). Plumbagin was the most potent quinone, with IC50 values from 0.06 μM (MCF-7 breast cancer cells) to 1.14 μM (A549 lung cancer cells), including 0.27 μM in mesothelioma cells. Doxorubicin was lower in four of six lines. Rapanone's lowest IC50 was 2.27 μM, in mesothelioma cells. In breast cancer cells, both compounds increased dying cells without changing caspase 3/7 or 9 activity at 6 hours. The authors linked plumbagin's effect to reactive oxygen species and rapanone's to loss of mitochondrial membrane potential, and called for further study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment testing compounds for toxicity to cancer cells
• Who was studied: Six human cancer cell lines (A549 lung, SPC212 mesothelioma, DLD-1 and Caco-2 colorectal, HepG2 liver, MCF-7 breast) and one normal cell line (CRL2120 human skin fibroblasts); no human or animal subjects
• Exposure: 14 naturally occurring quinones (3 anthraquinones, 1 naphthoquinone, 10 benzoquinones) from a chemical bank at the University of Nairobi, with doxorubicin as reference drug; asbestos was not studied
• Main results:
  • Compounds 2 (emodin), 4 (plumbagin), 9 (rapanone), 10, 11 and 13, and doxorubicin, had IC50 values below 100 μM in all six cancer cell lines
  • Compounds 3, 5 and 12 were not active against the cancer cell lines, with IC50 values above 120 μM in all of them
  • Compound 5 had an IC50 of 95.51 μM in the normal CRL2120 fibroblasts (Table 1)
  • Plumbagin IC50 ranged from 0.06 μM (MCF-7 breast cancer cells) to 1.14 μM (A549 lung cancer cells)
  • In SPC212 mesothelioma cells, plumbagin IC50 was 0.27 μM (selectivity index 250.59)
  • Doxorubicin IC50 ranged from 0.07 μM (SPC212 cells) to 1.01 μM (A549 cells); plumbagin's IC50 was lower than doxorubicin's only in Caco-2 and MCF-7 cells
  • Rapanone's lowest IC50 was 2.27 μM, in SPC212 mesothelioma cells
  • Compound 11 and doxorubicin were in many cases slightly more toxic to normal CRL2120 fibroblasts than to cancer cells
  • In MCF-7 breast cancer cells, the share of cells in the sub-G0/G1 phase (a sign of cell death) rose from 10.4% to 20.4% with plumbagin and from 34.8% to 43.2% with rapanone, at one quarter of the IC50 and at the IC50 respectively
  • In MCF-7 cells treated for 6 hours, neither compound changed caspase 3/7 or caspase 9 activity
  • In MCF-7 cells, rapanone caused up to 88.1% loss of mitochondrial membrane potential at IC50, and plumbagin caused 12.2%
  • In MCF-7 cells, plumbagin raised reactive oxygen species levels more than 3-fold at IC50 compared with untreated cells; rapanone raised them less than 2-fold
  • The authors attributed apoptosis in MCF-7 cells to increased reactive oxygen species for plumbagin and to loss of mitochondrial membrane potential for rapanone
• The authors' conclusion: The authors concluded that the studied compounds, especially the most active ones, deserve more investigation toward developing new cytotoxic drugs against cancers

Topics

Medical terms in this study, explained in our Lexicon: Carcinoma, Chemotherapy, Fibroblast, Reactive Oxygen Species (ROS), Doxorubicin, Adenocarcinoma, Small Cell Lung Cancer, A549 Cells.

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