Cytotoxicity of the methanol extracts of Elephantopus mollis, Kalanchoe crenata and 4 other Cameroonian medicinal plants towards human carcinoma cells

Our plain-English summary of Cytotoxicity of the methanol extracts of Elephantopus mollis, Kalanchoe crenata and 4 other Cameroonian medicinal plants towards human carcinoma cells, by V. Kuete, F.W. Fokou, O. Karaosmanoğlu, et al (BMC Complementary and Alternative Medicine, 2017).

The study

• Authors: V. Kuete, F.W. Fokou, O. Karaosmanoğlu, V.P. Beng, H. Sivas
• Journal: BMC Complementary and Alternative Medicine
• Published: 2017;17(1):280
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Cancer still constitutes one of the major health concerns globally, causing serious threats on patients, their families, and the healthcare system.

Methods: In this study, the cytotoxicity of the methanol extract of Elephantopus mollis whole plant (EMW), Enantia chlorantha bark (ECB), Kalanchoe crenata leaves (KCL), Lophira alata bark (LAB), Millettia macrophylla leaves (MML) and Phragmanthera capitata leaves (PCL) towards five human solid cancer cell lines and normal CRL2120 fibroblasts, was evaluated. Extracts were subjected to qualitative chemical screening of their secondary metabolite contents using standard methods. The cytotoxicity of samples was evaluated using neutral red uptake (NR) assay meanwhile caspase activation was detected by caspase-Glo assay. Flow cytometry was used to analyze the cell cycle distribution and the mitochondrial membrane potential (MMP) whilst spectrophotometry was used to measure the levels of reactive oxygen species (ROS).

Results: Phytochemical analysis revealed the presence of polyphenols, triterpenes and sterols in all extracts. The IC50 values of the best samples ranged from 3.29 μg/mL (towards DLD-1 colorectal adenocarcinoma cells) to 24.38 μg/mL (against small lung cancer A549 cells) for EMW, from 2.33 μg/mL (mesothelioma SPC212 cells) to 28.96 μg/mL (HepG2 hepatocarcinoma) for KCL, and from 0.04 μg/mL (towards SPC212 cells) to 0.55 μg/mL (towards A549 cells) for doxorubicin. EMW induced apoptosis in MCF-7 cells mediated by MMP loss and increased ROS production whilst KCL induced apoptosis via ROS production.

Conclusion: This study provides evidences of the cytotoxicity of the tested plant extract and highlights the good activity of Elephantopus mollis and Kalanchoe crenata. They deserve more exploration to develop novel cytotoxic drugs.

In plain English

This laboratory study tested methanol extracts of six Cameroonian medicinal plants on human cells grown in dishes. No people were studied. The cells included SPC212 mesothelioma cells, four other cancer lines and normal skin fibroblasts. Doxorubicin, a cancer drug, was the comparison. Against the mesothelioma cells, the Kalanchoe crenata leaf extract reached its IC50 (the concentration that cut cell growth by half) at 2.33 μg/mL. The Elephantopus mollis whole-plant extract reached it at 4.05 μg/mL, and doxorubicin at 0.04 μg/mL. The Phragmanthera capitata extract reached no IC50 up to 40 μg/mL in any cancer cell line. Each plant extract's measurable cancer-cell IC50 was lower than in the normal cells, where no extract reached an IC50 up to 40 μg/mL. In breast cancer (MCF-7) cells, the two most active extracts raised the share of cells the authors counted as apoptotic. At IC50 doses after 24 hours, they also raised reactive oxygen species more than threefold; no caspase activation was seen after 6 hours. The authors concluded these extracts deserve more exploration toward new drugs. They noted that reactive oxygen species alone cannot identify apoptosis.

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 plant extracts for toxicity to cancer cells
• Who was studied: Five human cancer cell lines (SPC212 mesothelioma, A549 non-small cell lung cancer, HepG2 hepatocarcinoma, MCF-7 breast adenocarcinoma, DLD-1 colorectal adenocarcinoma) and normal CRL2120 human skin fibroblasts; no human subjects
• Exposure: Methanol extracts of six Cameroonian medicinal plants (Elephantopus mollis whole plant, Enantia chlorantha bark, Kalanchoe crenata leaves, Lophira alata bark, Millettia macrophylla leaves, Phragmanthera capitata leaves), tested up to 40 μg/mL for 72 h, with doxorubicin as the reference drug; no asbestos exposure
• Main results:
  • Kalanchoe crenata leaf extract (KCL) IC50 ranged from 2.33 μg/mL in SPC212 mesothelioma cells to 28.96 μg/mL in HepG2 cells
  • Elephantopus mollis whole-plant extract (EMW) IC50 in SPC212 mesothelioma cells was 4.05 ± 0.69 μg/mL; across cancer lines its IC50 ranged from 3.29 μg/mL (DLD-1) to 24.38 μg/mL (A549)
  • Doxorubicin IC50 ranged from 0.04 μg/mL in SPC212 cells to 0.55 μg/mL in A549 cells
  • Phragmanthera capitata leaf extract (PCL) reached no IC50 at up to 40 μg/mL in any cancer cell line
  • No plant extract reached an IC50 in normal CRL2120 fibroblasts at up to 40 μg/mL, so every measurable plant-extract cancer-cell IC50 was lower; the authors reported selectivity indexes above 1.00 for the extracts. PCL had no measurable IC50 in any cell line, so its relative toxicity could not be determined from the table. This statement does not apply to doxorubicin, whose IC50 in A549 cells (0.55 μg/mL) was higher than in the normal fibroblasts (0.32 μg/mL).
  • In MCF-7 breast cancer cells, sub-G0/G1 (apoptotic) cells increased from 11.8% to 31% with KCL and from 28.8% to 83.4% with EMW (from one-quarter IC50 to IC50), versus 3.1% in untreated cells
  • No activation of caspase 3/7 or caspase 9 was seen in MCF-7 cells after 6 h treatment with EMW, KCL or doxorubicin at half-IC50 and IC50
  • Mitochondrial membrane potential loss in MCF-7 cells ranged from 33.9% to 90.1% with EMW and from 11.8% to 19.7% with KCL
  • After 24 h, EMW and KCL raised reactive oxygen species levels in MCF-7 cells more than threefold at IC50 compared with untreated cells; doxorubicin raised them more than twofold
• The authors' conclusion: The authors concluded that the three most active extracts (E. mollis whole plant, K. crenata leaves, M. macrophylla leaves) can be used in the management of malignant diseases and deserve more exploration to isolate active constituents and develop new cytotoxic drugs
• Limitations the authors state:
  • The authors stated that reactive oxygen species production alone is not enough to identify apoptosis, and that further tests of apoptosis-related molecules are planned

Topics

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

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