Galenia africana plant extract exhibits cytotoxicity in breast cancer cells by inducing multiple programmed cell death pathways

Mohamed, Luqmaan; Chakraborty, Suparna; ArulJothi, K.N.; Mabasa, Lawrence; Sayah, Kenza; Costa-Lotufo, Letı́cia V.; Jardine, Anwar; Prince, Sharon

doi:10.1016/j.jsps.2020.08.004

Cited by 16 publications

(14 citation statements)

References 40 publications

(45 reference statements)

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“…In agreement with the present finding, various studies reported plant extracts with similar effects in various cancer cell lines, including MCF-7 and MDA-MB-231 cell lines [ 37 , 38 ]. This finding is consistent with the report that an extract from Galenia africana inhibited the cell migration by downregulating the mesenchymal markers, vimentin and β-catenin, and upregulating E-cadherin, a well characterized epithelial marker [ 39 ]. Since cell migration involves the transition of epithelial cells into motile mesenchymal cells [ 40 ] and thus promotes CSC migration, contributing to the reconstitution of metastatic cancer at distant sites [ 41 , 42 ], the present finding implicates that the bioactive fractions may contribute to reducing the metastatic burden of breast cancer.…”

Section: Discussionsupporting

confidence: 93%

Solvent fractions of selected Ethiopian medicinal plants used in traditional breast cancer treatment inhibit cancer stem cells in a breast cancer cell line

Tuasha

Seifu

Gadisa

et al. 2020

BMC Complement Med Ther

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Background The incidence and mortality of breast cancer in women is increasing worldwide. Breast cancer contains a subpopulation of cells known as cancer stem cells (CSCs). The CSCs are believed to be responsible for chemotherapeutic resistance and are also involved in tumor initiation, progression, evolution, and metastasis to distant sites. The present study aimed to investigate the anti-CSC potential of selected Ethiopian medicinal plants traditionally used for breast cancer treatment. Methods The solvent fractions of three medicinal plants (the ethyl acetate fraction of Vernonia leopoldi, the aqueous fraction of Sideroxylon oxyacanthum, and the chloroform fraction of Clematis simensis) resulting from the methanolic crude extracts were selected based on their previously demonstrated cytotoxic effects on breast cancer cell lines. The effect of these solvent fractions on the status of the cancer stem cell subpopulation of the JIMT-1 cell line was assessed by flow cytometric evaluation of the proportion of aldehyde dehydrogenase positive cells and by measuring colony forming efficiency in a serum-free soft agar assay after treatment. Effects on cell migration using a wound healing assay and on tumor necrosis factor-α-induced translocation of nuclear factor-kappa B to the cell nucleus were also investigated. Results The solvent fractions showed a dose-dependent reduction in the aldehyde dehydrogenase positive subpopulation of JIMT-1 cells. The chloroform fraction of C. simensis (80 μg/mL) completely blocked colony formation of JIMT-1 cells. The wound healing assay showed that all fractions significantly reduced cell migration. The ethyl acetate fraction of V. leopoldi (0.87 μg/mL) significantly inhibited tumor necrosis factor-α-induced nuclear factor-kappa B translocation to the nucleus. Conclusion The solvent fractions of the medicinal plants showed desirable activities against breast cancer stem cells in the JIMT-1 cell line, which warrants further studies.

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Section: Discussionsupporting

confidence: 93%

Solvent fractions of selected Ethiopian medicinal plants used in traditional breast cancer treatment inhibit cancer stem cells in a breast cancer cell line

Tuasha

Seifu

Gadisa

et al. 2020

BMC Complement Med Ther

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“…This shows that the cell viability of A375 cells was affected in a time and dose-dependent manner. A similar study also reported that G. africana could reduce cell viability of malignant breast cancer cell lines MCF-7 and MDA-MB-231 (IC 50 values of 114.0 and 130.5 µg/mL) in a dose-dependent manner, respectively [34]. This further substantiating the extract's anti-proliferative effects.…”

Section: Discussionsupporting

confidence: 68%

“…This suggests that the extract is not harmful to healthy cells at concentrations between 100-200 µg/mL after 24, 48 and 72 h of exposure. A similar study has also reported that G. africana was less effective in reducing the cell viability of non-malignant fibroblast and breast epithelial (IC 50 values of 185.5 and 159.8 µg/mL), respectively [34]. While another study showed that G. africana was non-toxic as it did not induce a hypersensitivity response or cause any dermal sensitization to the epidermis [30].…”

Section: Discussionmentioning

confidence: 83%

“…The G. africana ethanol extracts have been reported to contain flavonoid compounds which could potentially activate programmed cell death mechanisms by acting as prooxidants and inducing mitochondria-mediated apoptosis in cancer cells [17,20,21]. A recent study by Mohamed et al [34] reported that the ethanolic extracts of G. africana had antiproliferative properties and induced apoptosis against breast cancer cells (MCF-7 and MDA-MB-231). Previous work has also investigated the plant's immunomodulatory potential and its anti-tuberculosis effects [21,31,35].…”

Section: Discussionmentioning

confidence: 99%

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In Vitro Comparison of the Anti-Proliferative Effects of Galenia africana on Human Skin Cell Lines

et al. 2021

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Malignant melanoma is the major cause of skin cancer-related deaths. Surgery in combination with radiotherapy, immunotherapy or chemotherapy is used to eradicate cancer cells, however, this treatment option is limited by the tolerance of the surrounding healthy tissue. The extracts from Galenia africana have been shown to possess anti-cancer flavonoid compounds and can be a safer and cost-effective alternative treatment. The study aimed to compare the anti-proliferative effects of G. africana on human skin cells (HaCaT) and human malignant melanoma cells (A375). The cells were exposed to various concentrations of the G. africana extract at different times. In vitro assays were employed to determine cell viability and cytotoxicity. Hoechst 33342 staining was performed to observe the nuclear changes, including apoptosis. G. africana significantly reduced the cell viability of the A375 cells in a dose and time-dependent manner, while having no effect on the HaCaT cells. The A375 cells displayed nuclear condensation, brightly stained nuclei and nuclear fragmentation indicative of apoptosis. This suggests a clinical rationale for the use of G. africana as a potential anti-melanoma agent offering efficacy and low toxicity. This study provides new insights for future work on investigating the utilization of G. africana in malignant melanoma treatment.

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“…The ability of cancer cells to migrate from the primary site and form tumors at the distal sites is the major cause of morbidity in cancer patients 36 . Therefore, we next assessed the anti‐migratory effect of MBE using the wound‐healing assay.…”

Section: Resultsmentioning

confidence: 99%

In vitro antimetastatic activity of Momordica balsamina crude acetone extract in HT‐29 human colon cancer cells

Serala

Steenkamp

Mampuru

et al. 2021

Environmental Toxicology

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Plant‐derived compounds and/or extracts have proven to be beneficial for the treatment of a broad spectrum of cancers with minimal side effects. In this study, we investigated whether a crude acetone extract of Momordica balsamina (MBE) can interfere with the metastatic ability of HT‐29 colorectal cancer (CRC) cells. The phytochemical composition of MBE was determined by ultra‐performance liquid chromatography and cytotoxic effects by the MTT and acridine orange/ethidium bromide staining assays. The effect of MBE on the formation of reactive oxygen species was assessed using the DCFH2‐DA assay. Wound healing assay, transwell cell invasion assay, cell adhesion assay, and the extracellular matrix‐cell adhesion array were used to assess the antimetastatic effects of MBE. The effect of MBE on the expression of TNF‐α, NF‐κB, TIMP‐3, MMP‐2, and MMP‐9 was assessed by western blot analysis. Our results showed that MBE consists of a mixture of compounds without a known anticancer activity in CRC and exhibits cytotoxicity against HT‐29 cells. MBE also suppressed reactive oxygen species formation, cell invasion, cell migration, and cell adhesion. The reduction of cell invasion was associated with the downregulation of TNF‐α, NF‐κB, MMP2, and MMP9 and upregulation of TIMP‐3 proteins. We concluded that MBE inhibits the metastatic ability of HT‐29 CRC cells in vitro.

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Galenia africana plant extract exhibits cytotoxicity in breast cancer cells by inducing multiple programmed cell death pathways

Abstract: Graphical abstract

Cited by 16 publications

References 40 publications

Solvent fractions of selected Ethiopian medicinal plants used in traditional breast cancer treatment inhibit cancer stem cells in a breast cancer cell line

Solvent fractions of selected Ethiopian medicinal plants used in traditional breast cancer treatment inhibit cancer stem cells in a breast cancer cell line

In Vitro Comparison of the Anti-Proliferative Effects of Galenia africana on Human Skin Cell Lines

In vitro antimetastatic activity of Momordica balsamina crude acetone extract in HT‐29 human colon cancer cells

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