Flavonoids from the stems of Millettia pachyloba Drake mediate cytotoxic activity through apoptosis and autophagy in cancer cells

Yan, Wei; Yang, Jianhong; Tang, Huan; Xue, Linlin; Chen, Kai; Wang, Lun; Zhao, Min; Tang, Minghai; Peng, Aihua; Long, Chaofeng; Chen, Xiaoxin; Ye, Haoyu; Chen, Lijuan

doi:10.1016/j.jare.2019.06.002

Cited by 23 publications

(11 citation statements)

References 49 publications

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“…A number of studies have revealed that flavonoids could induce apoptosis in various cancer cells [24][25][26]. In the present study, we also detected obvious apoptosis in HeLa cells upon the administration of flavonoids in A. conyzoides.…”

Section: Discussionsupporting

confidence: 76%

Flavonoids in Ageratum conyzoides L. Exert Potent Antitumor Effects on Human Cervical Adenocarcinoma HeLa Cells In Vitro and In Vivo

Zeyan

Lin

Shen

et al. 2020

BioMed Research International

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The Ageratum conyzoides L. (A. conyzoides) is commonly used as a traditional medicine, and its antitumor effects have also been studied. However, the functional roles of flavonoids in A. conyzoides in antitumor activities have not been clarified. The present study is aimed at investigating the biological effects of flavonoids in A. conyzoides on human cervical adenocarcinoma. Firstly, we detected that flavonoids in A. conyzoides significantly inhibited the proliferation, invasion, migration, and clonality of human cervical adenocarcinoma HeLa cells in vitro. Furthermore, we found that flavonoids in A. conyzoides induced significant S phase arrest and apoptosis and obviously decreased the intracellular reactive oxygen species (ROS) level in HeLa cells. Finally, we found that flavonoids in A. conyzoides significantly inhibited the HeLa xenograft tumor growth and epithelial-mesenchymal transition (EMT) in vivo. In conclusion, our results demonstrated the obvious antitumor effects of flavonoids in A. conyzoides on HeLa cells, suggesting that flavonoids in A. conyzoides could be provided as a novel therapeutic compound for human cervical adenocarcinoma.

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Section: Discussionsupporting

confidence: 76%

Flavonoids in Ageratum conyzoides L. Exert Potent Antitumor Effects on Human Cervical Adenocarcinoma HeLa Cells In Vitro and In Vivo

Zeyan

Lin

Shen

et al. 2020

BioMed Research International

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“…In addition, isoflavones extracted from M. taiwaniana have shown cancer chemopreventive activities [20]. Durmillone isolated from M. pachyloba Drake induced apoptosis and autophagy in Hela and MCF-7 cells [21]. In this study, we demonstrated that two isoflavones, ferrugone and DMI, isolated from M. ferruginea, induced apoptotic cell death in human ovarian cancer cells.…”

Section: Discussionmentioning

confidence: 52%

Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

et al. 2020

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The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3’,4’-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.

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“… 25 To further determine how HTPM reduces the viability of breast cancer cells, Annexin V-FITC/PI double staining was performed to assess the extent and mode of cell death. 35 In this study, MDA-MB-231 cells were treated with various concentrations of HPTM ranging from 0 to 50 nM, and then the percentage of apoptotic cells was quantitatively analyzed by flow cytometry. As depicted in Figure 5A – B , HTPM lead to apoptosis, including early and late apoptosis after exposure for 24 h. The apoptotic levels of MDA-MB-231 cells were gradually enhanced with increased treatment concentrations.…”

Section: Resultsmentioning

confidence: 99%

Encapsulating Halofuginone Hydrobromide in TPGS Polymeric Micelles Enhances Efficacy Against Triple-Negative Breast Cancer Cells

Zuo¹,

Zhang²,

Song³

et al. 2021

IJN

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Background Halofuginone hydrobromide (HF) is a synthetic analogue of the naturally occurring quinazolinone alkaloid febrifugine, which has potential therapeutic effects against breast cancer, however, its poor water solubility greatly limits its pharmaceutical application. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of vitamin E, which can self-assemble to form polymeric micelles (PMs) for encapsulating insoluble anti-tumor drugs, thereby effectively enhancing their anti-cancer effects. Methods HF-loaded TPGS PMs (HTPMs) were manufactured using a thin-film hydration technique, followed by a series of characterizations, including the hydrodynamic diameter (HD), zeta potential (ZP), stability, drug loading (DL), encapsulation efficiency (EE), and in vitro drug release. The anti-cancer effects and potential mechanism of HTPMs were investigated in the breast cell lines MDA-MB-231 and MCF-7, and normal breast epithelial cell line Eph-ev. The breast cancer-bearing BALB/c nude mouse model was successfully established by subcutaneous injection of MDA-MB-231 cells and used to evaluate the in vivo therapeutic effect and safety of the HTPMs. Results The optimized HTPMs had an HD of 17.8±0.5 nm and ZP of 14.40±0.1 mV. These PMs exhibited DL of 12.94 ± 0.46% and EE of 90.6 ± 0.85%, along with excellent storage stability, dilution tolerance and sustained drug release in pH-dependent manner within 24 h compared to free HF. Additionally, the HTPMs had stronger inhibitory effects than free HF and paclitaxel against MDA-MB-231 triple-negative breast cancer cells, and little toxicity in normal breast epithelial Eph-ev cells. The HTPMs induced cell cycle arrest and apoptosis of MDA-MB-231 by disrupting the mitochondrial membrane potential and enhancing reactive oxygen species formation. Evaluation of in vivo anti-tumor efficacy demonstrated that HTPMs exerted a stronger tumor inhibition rate (68.17%) than free HF, and exhibited excellent biocompatibility. Conclusion The findings from this study indicate that HTPMs holds great clinical potential for treating triple-negative breast cancer.

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Flavonoids from the stems of Millettia pachyloba Drake mediate cytotoxic activity through apoptosis and autophagy in cancer cells

Abstract: Graphical abstract

Cited by 23 publications

References 49 publications

Flavonoids in Ageratum conyzoides L. Exert Potent Antitumor Effects on Human Cervical Adenocarcinoma HeLa Cells In Vitro and In Vivo

Flavonoids in Ageratum conyzoides L. Exert Potent Antitumor Effects on Human Cervical Adenocarcinoma HeLa Cells In Vitro and In Vivo

Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

Encapsulating Halofuginone Hydrobromide in TPGS Polymeric Micelles Enhances Efficacy Against Triple-Negative Breast Cancer Cells

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