Combined treatment of polygonatum and Scutellaria baicalensis suppresses lung cancer cell proliferation through inducing ferroptosis
Objective: To investigate the effects of combined treatment of Scutellaria baicalensis (SB) and polygonatum (HH) for lung cancer and explore the underlying mechanism. Purpose: The study was designed to investigate the anti-tumor effect of HH and reveal its mechanisms. Methods: Based on the Tradition...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Phytomedicine Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031323000787 |
| _version_ | 1797627133345923072 |
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| author | Wen Zhang Jing Jin Chuan-Wu Cao Fei Wang Hong Zhai Tian-Sheng Zheng Li-Hong Fan |
| author_facet | Wen Zhang Jing Jin Chuan-Wu Cao Fei Wang Hong Zhai Tian-Sheng Zheng Li-Hong Fan |
| author_sort | Wen Zhang |
| collection | DOAJ |
| description | Objective: To investigate the effects of combined treatment of Scutellaria baicalensis (SB) and polygonatum (HH) for lung cancer and explore the underlying mechanism. Purpose: The study was designed to investigate the anti-tumor effect of HH and reveal its mechanisms. Methods: Based on the Traditional Chinese Medicine (TCM) theory and network pharmacological analysis. The inhibitory effect of HH on the proliferation of A549 and LLC lung cancer cells was predicted by CCK8 assay in a subcutaneous tumor model in vivo. Tumor tissues were collected for proteomics, qPCR and immunohistochemistry assays. A549 and LLC cell proliferation was detected by CCK8 assay after treatment with HH combined with ferroptosis inhibitors and ferroptosis inducer Erastin for 48 h respectively. The expression of Transferrin Receptor (TFRC) was detected by qPCR and Western Blot. Changes in free iron content and lipid peroxide in cytoplasm and mitochondria were observed by laser confocal microscopy. Changes in Mitochondrial Membrane Potential (MMP, Δψm) and ROS content were detected by flow cytometry. Results: Search of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database demonstrated that HH played a role in lung cancer treatment. CCK8 assay showed that lung cancer cell proliferation was inhibited by HH in a dose-dependent manner. The animal experiment results showed that the tumor volume in HH-treated group was significantly smaller than that in Control group in the LLC allograft model (P<0.01). The expression level of TFRC in HH-treated group was higher than that in Control group, which was verified by proteomics, qPCR assay and immunohistochemistry. Two ferroptosis specific inhibitors could block HH-induced ferroptosis (P<0.05). Compared with Control group, free iron and lipid peroxide contents were significantly increased in cytoplasm and mitochondria while MMP was decreased and the level of ROS was augmented in HH group (P<0.01). Conclusion: HH increased the content of free iron and lipid peroxide in cytoplasm and mitochondria by upregulating the expression of TFRC in lung cancer cells, which further led to the accumulation of lipid peroxide, caused mitochondrial dysfunction, and finally induced ferroptosis in lung cancer cells. |
| first_indexed | 2024-03-11T10:20:04Z |
| format | Article |
| id | doaj.art-c9fc6d4712464ca0b4971cb3c80691da |
| institution | Directory Open Access Journal |
| issn | 2667-0313 |
| language | English |
| last_indexed | 2024-03-11T10:20:04Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
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| series | Phytomedicine Plus |
| spelling | doaj.art-c9fc6d4712464ca0b4971cb3c80691da2023-11-16T06:11:09ZengElsevierPhytomedicine Plus2667-03132023-11-0134100482Combined treatment of polygonatum and Scutellaria baicalensis suppresses lung cancer cell proliferation through inducing ferroptosisWen Zhang0Jing Jin1Chuan-Wu Cao2Fei Wang3Hong Zhai4Tian-Sheng Zheng5Li-Hong Fan6Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China“One Belt and One way” International Joint Laboratory, ChinaIntegrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaIntegrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; “One Belt and One way” International Joint Laboratory, China; Integrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Corresponding author at: Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China.Objective: To investigate the effects of combined treatment of Scutellaria baicalensis (SB) and polygonatum (HH) for lung cancer and explore the underlying mechanism. Purpose: The study was designed to investigate the anti-tumor effect of HH and reveal its mechanisms. Methods: Based on the Traditional Chinese Medicine (TCM) theory and network pharmacological analysis. The inhibitory effect of HH on the proliferation of A549 and LLC lung cancer cells was predicted by CCK8 assay in a subcutaneous tumor model in vivo. Tumor tissues were collected for proteomics, qPCR and immunohistochemistry assays. A549 and LLC cell proliferation was detected by CCK8 assay after treatment with HH combined with ferroptosis inhibitors and ferroptosis inducer Erastin for 48 h respectively. The expression of Transferrin Receptor (TFRC) was detected by qPCR and Western Blot. Changes in free iron content and lipid peroxide in cytoplasm and mitochondria were observed by laser confocal microscopy. Changes in Mitochondrial Membrane Potential (MMP, Δψm) and ROS content were detected by flow cytometry. Results: Search of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database demonstrated that HH played a role in lung cancer treatment. CCK8 assay showed that lung cancer cell proliferation was inhibited by HH in a dose-dependent manner. The animal experiment results showed that the tumor volume in HH-treated group was significantly smaller than that in Control group in the LLC allograft model (P<0.01). The expression level of TFRC in HH-treated group was higher than that in Control group, which was verified by proteomics, qPCR assay and immunohistochemistry. Two ferroptosis specific inhibitors could block HH-induced ferroptosis (P<0.05). Compared with Control group, free iron and lipid peroxide contents were significantly increased in cytoplasm and mitochondria while MMP was decreased and the level of ROS was augmented in HH group (P<0.01). Conclusion: HH increased the content of free iron and lipid peroxide in cytoplasm and mitochondria by upregulating the expression of TFRC in lung cancer cells, which further led to the accumulation of lipid peroxide, caused mitochondrial dysfunction, and finally induced ferroptosis in lung cancer cells.http://www.sciencedirect.com/science/article/pii/S2667031323000787Lung cancerPolygonatumScutellaria baicalensis (SB)FerroptosisMitochondriaTFRC |
| spellingShingle | Wen Zhang Jing Jin Chuan-Wu Cao Fei Wang Hong Zhai Tian-Sheng Zheng Li-Hong Fan Combined treatment of polygonatum and Scutellaria baicalensis suppresses lung cancer cell proliferation through inducing ferroptosis Phytomedicine Plus Lung cancer Polygonatum Scutellaria baicalensis (SB) Ferroptosis Mitochondria TFRC |
| title | Combined treatment of polygonatum and Scutellaria baicalensis suppresses lung cancer cell proliferation through inducing ferroptosis |
| title_full | Combined treatment of polygonatum and Scutellaria baicalensis suppresses lung cancer cell proliferation through inducing ferroptosis |
| title_fullStr | Combined treatment of polygonatum and Scutellaria baicalensis suppresses lung cancer cell proliferation through inducing ferroptosis |
| title_full_unstemmed | Combined treatment of polygonatum and Scutellaria baicalensis suppresses lung cancer cell proliferation through inducing ferroptosis |
| title_short | Combined treatment of polygonatum and Scutellaria baicalensis suppresses lung cancer cell proliferation through inducing ferroptosis |
| title_sort | combined treatment of polygonatum and scutellaria baicalensis suppresses lung cancer cell proliferation through inducing ferroptosis |
| topic | Lung cancer Polygonatum Scutellaria baicalensis (SB) Ferroptosis Mitochondria TFRC |
| url | http://www.sciencedirect.com/science/article/pii/S2667031323000787 |
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