Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage

Yu, Tsan-Jung; Tang, Jen‐Yang; Lin, Li‐Ching; Lien, Wan-Ju; Cheng, Yuan-Bin; Chang, Fang‐Rong; Ou‐Yang, Fu; Chang, Hsueh‐Wei

doi:10.3390/antiox9090873

Cited by 20 publications

(11 citation statements)

References 42 publications

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“…To provide a comparison with the clinically used anticancer drug cisplatin, the IC 50 value for cisplatin at 24 h in the MTS assay for SKBR3 cells was 49.8 μM [ 34 ]. The IC 50 concentrations for 48 h cisplatin in the ATP assay were 4.9, 17.9, and 26.9 μM for SKBR3, MCF7, and MDA-MB-231 cells, respectively [ 35 ]. For comparison, the IC 50 concentrations for 24 h PHA in the ATP assay were 4.18, 3.12, and 6.15 μM for SKBR3, MCF7, and MDA-MB-231 cells, respectively ( Figure 1 A).…”

Section: Discussionmentioning

confidence: 99%

Physalis peruviana-Derived Physapruin A (PHA) Inhibits Breast Cancer Cell Proliferation and Induces Oxidative-Stress-Mediated Apoptosis and DNA Damage

Cheng

Lin

et al. 2021

Antioxidants

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Breast cancer expresses clinically heterogeneous characteristics and requires multipurpose drug development for curing the different tumor subtypes. Many withanolides have been isolated from Physalis species showing anticancer effects, but the anticancer function of physapruin A (PHA) has rarely been investigated. In this study, the anticancer properties of PHA in breast cancer cells were examined by concentration and time-course experiments. In terms of cellular ATP content, PHA inhibited the proliferation of three kinds of breast cancer cells: MCF7 (estrogen receptor (ER)+, progesterone receptor (PR)+/−, human epidermal growth factor receptor 2 (HER2)−), SKBR3 (ER−/PR−/HER2+), and MDA-MB-231 (triple-negative). Moreover, PHA induced G2/M arrest in MCF7 and MDA-MB-231 cells. In terms of flow cytometry, PHA induced the generation of reactive oxygen species (ROS), the generation of mitochondrial superoxide, mitochondrial membrane potential depletion, and γH2AX-detected DNA damage in breast cancer MCF7 and MDA-MB-231 cells, which were suppressed by the ROS inhibitor N-acetylcysteine (NAC). In terms of flow cytometry and Western blotting, PHA induced apoptotic expression (annexin V, and intrinsic and extrinsic apoptotic signaling), which was suppressed by NAC and an apoptosis inhibitor (Z-VAD-FMK), in breast cancer cells. Therefore, PHA is a potential anti-breast-cancer natural product that modulates the oxidative-stress response, cell-cycle disturbance, apoptosis, and γH2AX-detected DNA damage.

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Section: Discussionmentioning

confidence: 99%

Physalis peruviana-Derived Physapruin A (PHA) Inhibits Breast Cancer Cell Proliferation and Induces Oxidative-Stress-Mediated Apoptosis and DNA Damage

Cheng

Lin

et al. 2021

Antioxidants

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“…In addition, cell cycle disturbance may lead to apoptosis. For example, ginsenoside Rf [ 35 ], sinularin [ 36 ], curcumin [ 37 ], and withanolide C [ 38 ] induce G2/M arrest, which is frequently associated with apoptosis in cancer cells. Similarly, a combined treatment with UVC/CPC induces higher G2/M arrest than individual treatments (UVC or CPC) in oral cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Combined Treatment with Cryptocaryone and Ultraviolet C Promotes Antiproliferation and Apoptosis of Oral Cancer Cells

Wang

Chang

Tang

et al. 2022

IJMS

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Cryptocaryone (CPC) was previously reported as preferential for killing natural products in oral cancer cells. However, its radiosensitizing potential combined with ultraviolet C (UVC) cell killing of oral cancer cells remains unclear. This study evaluates the combined anti-proliferation effect and clarifies the mechanism of combined UVC/CPC effects on oral cancer cells. UVC/CPC shows higher anti-proliferation than individual and control treatments in a low cytotoxic environment on normal oral cells. Mechanistically, combined UVC/CPC generates high levels of reactive oxygen species and induces mitochondrial dysfunction by generating mitochondrial superoxide, increasing mitochondrial mass and causing the potential destruction of the mitochondrial membrane compared to individual treatments. Moreover, combined UVC/CPC causes higher G2/M arrest and triggers apoptosis, with greater evidence of cell cycle disturbance, annexin V, pancaspase, caspases 3/7 expression or activity in oral cancer cells than individual treatments. Western blotting further indicates that UVC/CPC induces overexpression for cleaved types of poly (ADP-ribose) polymerase and caspase 3 more than individual treatments. Additionally, UVC/CPC highly induces γH2AX and 8-hydroxy-2’-deoxyguanosine adducts as DNA damage in oral cancer cells. Taken together, CPC shows a radiosensitizing anti-proliferation effect on UVC irradiated oral cancer cells with combined effects through oxidative stress, apoptosis and DNA damage.

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“…Previous reports have suggested that excessive production of ROS by exogenous means is more harmful to cancer cells ( 22 ). For instance, increasing ROS by exogenous drugs can cause apoptosis, DNA damage, or mitochondrial dysfunction of several cancers, including colorectal cancer, oral cancers, and breast cancer cells ( 44 – 46 ). We found that the effect of CVBD in inducing GBM cell apoptosis is related to the increase of intracellular ROS.…”

Section: Discussionmentioning

confidence: 99%

Cyclovirobuxine D Induces Apoptosis and Mitochondrial Damage in Glioblastoma Cells Through ROS-Mediated Mitochondrial Translocation of Cofilin

Zhang

Duan

et al. 2021

Front. Oncol.

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BackgroundCyclovirobuxine D (CVBD), a steroidal alkaloid, has multiple pharmacological activities, including anti-cancer activity. However, the anti-cancer effect of CVBD on glioblastoma (GBM) has seldom been investigated. This study explores the activity of CVBD in inducing apoptosis of GBM cells, and examines the related mechanism in depth.MethodsGBM cell lines (T98G, U251) and normal human astrocytes (HA) were treated with CVBD. Cell viability was examined by CCK-8 assay, and cell proliferation was evaluated by cell colony formation counts. Apoptosis and mitochondrial superoxide were measured by flow cytometry. All protein expression levels were determined by Western blotting. JC-1 and CM-H2DCFDA probes were used to evaluate the mitochondrial membrane potential (MMP) change and intracellular ROS generation, respectively. The cell ultrastructure was observed by transmission electron microscope (TEM). Colocalization of cofilin and mitochondria were determined by immunofluorescence assay.ResultsCVBD showed a greater anti-proliferation effect on the GBM cell lines, T98G and U251, than normal human astrocytes in dose- and time-dependent manners. CVBD induced apoptosis and mitochondrial damage in GBM cells. We found that CVBD led to mitochondrial translocation of cofilin. Knockdown of cofilin attenuated CVBD-induced apoptosis and mitochondrial damage. Additionally, the generation of ROS and mitochondrial superoxide was also induced by CVBD in a dose-dependent manner. N-acetyl-L-cysteine (NAC) and mitoquinone (MitoQ) pre-treatment reverted CVBD-induced apoptosis and mitochondrial damage. MitoQ pretreatment was able to block the mitochondrial translocation of cofilin caused by CVBD.ConclusionsOur data revealed that CVBD induced apoptosis and mitochondrial damage in GBM cells. The underlying mechanism is related to mitochondrial translocation of cofilin caused by mitochondrial oxidant stress.

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Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage

Cited by 20 publications

References 42 publications

Physalis peruviana-Derived Physapruin A (PHA) Inhibits Breast Cancer Cell Proliferation and Induces Oxidative-Stress-Mediated Apoptosis and DNA Damage

Physalis peruviana-Derived Physapruin A (PHA) Inhibits Breast Cancer Cell Proliferation and Induces Oxidative-Stress-Mediated Apoptosis and DNA Damage

Combined Treatment with Cryptocaryone and Ultraviolet C Promotes Antiproliferation and Apoptosis of Oral Cancer Cells

Cyclovirobuxine D Induces Apoptosis and Mitochondrial Damage in Glioblastoma Cells Through ROS-Mediated Mitochondrial Translocation of Cofilin

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