Characteristics of the Cytotoxicity of Taraxacum mongolicum and Taraxacum formosanum in Human Breast Cancer Cells

Abstract

Breast cancer is a highly heterogeneous disease that has been clinically divided into three main subtypes: estrogen receptor (ER)- and progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER 2)-positive, and triple-negative breast cancer (TNBC). With its high metastatic potential and resistance to endocrine therapy, HER 2-targeted therapy, and chemotherapy, TNBC represents an enormous clinical challenge. The genus Taraxacum is used to treat breast cancer in traditional medicine. Here, we applied aqueous extracts from two Taraxacum species, T. mongolicum and T. formosanum, to compare their potential antitumor effects against three human breast cancer cell lines: MDA-MB-231 (ER-, PR-, and HER2-), ZR-75-1 (ER+, PR+/−, and HER2-), and MCF-7 (ER+, PR+, and HER2-). Our results show that T. mongolicum exerted cytotoxic effects against MDA-MB-231 cells, including the induction of apoptosis, the reduction of cell proliferation, the disruption of the mitochondrial membrane potential, and/or the downregulation of the oxygen consumption rate. Both T. mongolicum and T. formosanum decreased cell migration and colony formation in the three cell-lines and exerted suppressive effects on MCF-7 cell proliferation based on metabolic activity and BrdU incorporation, but an enhanced proliferation of ZR-75-1 cells based on BrdU incorporation. T. formosanum induced ribotoxic stress in MDA-MB-231and ZR-75-1 cells; T. mongolicum did not. In summary, these findings suggest that T. mongolicum showed greater cytotoxicity against all three tested breast cancer cell lines, especially the TNBC MDA-MB-231 cell line.

The therapeutic potential of natural metabolites in targeting endocrine-independent HER-2-negative breast cancer

“…The main groups of secondary metabolites reported to have anticancer properties in endocrine-independent HER-2-negative breast cancer are phenolics, alkaloids, and terpenoids ( Raman et al, 2018 ; Ding et al, 2020 ; Lee et al, 2020 ; Mazzei et al, 2020 ; Maungchanburi et al, 2021 ; Noh et al, 2021 ; Lin et al, 2022 ; Qi et al, 2022 ; Sancha et al, 2022 ; Youssef et al, 2022 ; Thilagavathi et al, 2023 ). Phenolics include simple phenols (phenolic acids and coumarins) and polyphenols (flavonoids and non-flavonoids such as tannins, lignans, and stilbenes).…”

“…The extraction process is usually carried out at room temperature in order to protect biologically active metabolites from degradation. Extracts derived from the biomass typically provide low yields of bioactive chemicals, which makes their isolation and purification time-consuming and expensive ( Mazzei et al, 2020 ; Lin et al, 2022 ). Therefore, the selection of the appropriate extraction process, experimental conditions, and solvent seems to be of paramount importance.…”

“… An overview of mechanistic effects of natural metabolites in endocrine-independent HER-2 negative breast cancer (created with BioRender). (A) Diagrammatic representation of the mechanistic findings: cell death induction ( Cheng et al, 2019 ; Guo and Pei, 2019 ; Nguyen et al, 2019 ; Zhang et al, 2019 ; Ding et al, 2020 ; Ho et al, 2020 ; Liu et al, 2020 ; Sánchez-Valdeolívar et al, 2020 ; Harikrishnan et al, 2021 ; Maungchanburi et al, 2021 ; Noh et al, 2021 ; Fouzat et al, 2022 ; Lin et al, 2022 ; Luo et al, 2022 ; Sancha et al, 2022 ; Sangpairoj et al, 2023 ), antiproliferative activity ( Alsaraf et al, 2019 ; Zwartsen et al, 2019 ; Collard et al, 2020 ; Jaglanian and Tsiani, 2020 ; Kalebar et al, 2020 ; Lee et al, 2020 ; Mazzei et al, 2020 ; Yang et al, 2021 ; Lin et al, 2022 ; Youssef et al, 2022 ; Kombiyil and Sivasithamparam, 2023 ) antimetastatic activity ( Hsu et al, 2020 ; Lee et al, 2020 ; Chen et al, 2022 ; Luo et al, 2022 ); antiangiogenic activity ( Utage et al, 2018 ; Hsu et al, 2020 ; Zunica et al, 2021 ), disrupted cancer cell metabolism ( Raman et al, 2018 ; Guerra et al, 2021 ; Yang et al, 2021 ; Chen et al, 2022 ; Ke et al, 2022 ), immunomodulation ( Kim et al, 2018 ; Zhao et al, 2020 ; 2021 ; Deng et al, 2021 ; Chen et al, 2022 ; Fouzat et al, 2022 ; Lv et al, 2022 ). (B) Each mechanism of anticancer activity is described in details and recently studied organisms as a source of secondary metabolites are presented (full species names including authorities and family are presented...…”

“…Programmed cell death is a broad and intricate concept encompassing a diverse array of mechanisms, including apoptosis, which occurs as a consequence of numerous changes in cancer cells. Some of these mechanisms have been identified for naturally-derived drugs ( Alsaraf et al, 2019 ; Cheng et al, 2019 ; Guo and Pei, 2019 ; Mendonca et al, 2019 ; Nguyen et al, 2019 ; Zhang et al, 2019 ; Ding et al, 2020 ; Ho et al, 2020 ; Jaglanian and Tsiani, 2020 ; Lee et al, 2020 ; Mazzei et al, 2020 ; Sánchez-Valdeolívar et al, 2020 ; Harikrishnan et al, 2021 ; Maungchanburi et al, 2021 ; Noh et al, 2021 ; Yang et al, 2021 ; Fouzat et al, 2022 ; Ke et al, 2022 ; Lin et al, 2022 ; Luo et al, 2022 ; Sancha et al, 2022 ; Sangpairoj et al, 2023 ) ( Figure 2 ). The exact mechanism leading to cell death is essential to be defined as it can predict drugs’ toxicity, efficacy or suggest potential effects of combining with other medications such as synergistic or complementary effect.…”

“…Ribotoxic stress refers to a cellular pathway that reacts to errors in translation, triggering the activation of p38 and c-Jun N-terminal kinases. This response leads to cell cycle arrest, the generation of inflammatory cytokines, and the initiation of apoptotic signaling ( Lin et al, 2022 ). Ferroptosis is an iron-dependent programmed cell death, distinct from apoptosis.…”