Water extract of sporoderm-broken spores of Ganoderma lucidum elicits dual antitumor effects by inhibiting p-STAT3/PD-L1 and promoting ferroptosis in castration-resistant prostate cancer
Prostate cancer (PCa) is one of the most common malignancies among male patients with cancer pathology worldwide. Owing to the inevitable development of irremediable castration-resistant prostate cancer (CRPC) following intervention with androgen deprivation therapy, new therapeutic strategies are i...
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Elsevier
2024-02-01
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| Series: | Journal of Functional Foods |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464624000203 |
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| author | Xumin Zhou Jiaqi Wang Yufei Guo Houhua Lai Shilong Cheng Zhongjie Chen Hua Li Qiang Li Xiangming Mao |
| author_facet | Xumin Zhou Jiaqi Wang Yufei Guo Houhua Lai Shilong Cheng Zhongjie Chen Hua Li Qiang Li Xiangming Mao |
| author_sort | Xumin Zhou |
| collection | DOAJ |
| description | Prostate cancer (PCa) is one of the most common malignancies among male patients with cancer pathology worldwide. Owing to the inevitable development of irremediable castration-resistant prostate cancer (CRPC) following intervention with androgen deprivation therapy, new therapeutic strategies are in great demand. Ganoderma lucidum, a medicinal fungus, has recently been reported to be a potential antitumor agent. However, whether the water extract of sporoderm-broken spores of G. lucidum (BSGWE), a special approach to obtain whole wall-broken spore extracts of G. lucidum, can inhibit castration-resistant prostate cancer (CRPC) has not been well characterized. In this study, we found that BSGWE inhibited cell proliferation, caused cell cycle arrest in G2/M phase, and promoted ferroptosis, which resulted in high levels of reactive oxygen species (ROS) in vitro and suppressed the growth of CRPC tumors in xenograft models. In addition, we reported that BSGWE inhibited STAT3 expression, which partly accounted for the inhibition of the transcription of PD-L1 and led to ferroptosis, manifested by the downregulation of SLC7A11 and GPX4 expression. Furthermore, BSGWE exhibited a synergistic effect with 5-fluorouracil (5-Fu) in chemotherapy of CRPC in vitro and in vivo. This study provides biological evidence that BSGWE is a novel STAT3 inhibitor that exerts anti-proliferation, pro-cell death, and pro-immunity effect and indicates a novel utilization of BSGWE in neoadjuvant chemotherapy of CRPC. |
| first_indexed | 2024-03-08T02:02:03Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-03-08T02:02:03Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-1e739c31116a4b289634cf6f8d2c93532024-02-14T05:14:29ZengElsevierJournal of Functional Foods1756-46462024-02-01113106018Water extract of sporoderm-broken spores of Ganoderma lucidum elicits dual antitumor effects by inhibiting p-STAT3/PD-L1 and promoting ferroptosis in castration-resistant prostate cancerXumin Zhou0Jiaqi Wang1Yufei Guo2Houhua Lai3Shilong Cheng4Zhongjie Chen5Hua Li6Qiang Li7Xiangming Mao8General Surgery Center Department of Thyroid Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, PR China; Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, P. R. China; Department of Pathogen Biology and Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease, School of Public Health, Southern Medical University, Guangzhou 510515, P. R. China; Corresponding authors at: General Surgery Center Department of Thyroid Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Central, Haizhu District, Guangzhou 510280, PR China.Department of of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, PR ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, P. R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, P. R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, P. R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, P. R. ChinaDepartment of Pathogen Biology and Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease, School of Public Health, Southern Medical University, Guangzhou 510515, P. R. China; Corresponding authors at: General Surgery Center Department of Thyroid Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Central, Haizhu District, Guangzhou 510280, PR China.General Surgery Center Department of Thyroid Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, PR China; Corresponding authors at: General Surgery Center Department of Thyroid Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Central, Haizhu District, Guangzhou 510280, PR China.Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, P. R. China; Corresponding authors at: General Surgery Center Department of Thyroid Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Central, Haizhu District, Guangzhou 510280, PR China.Prostate cancer (PCa) is one of the most common malignancies among male patients with cancer pathology worldwide. Owing to the inevitable development of irremediable castration-resistant prostate cancer (CRPC) following intervention with androgen deprivation therapy, new therapeutic strategies are in great demand. Ganoderma lucidum, a medicinal fungus, has recently been reported to be a potential antitumor agent. However, whether the water extract of sporoderm-broken spores of G. lucidum (BSGWE), a special approach to obtain whole wall-broken spore extracts of G. lucidum, can inhibit castration-resistant prostate cancer (CRPC) has not been well characterized. In this study, we found that BSGWE inhibited cell proliferation, caused cell cycle arrest in G2/M phase, and promoted ferroptosis, which resulted in high levels of reactive oxygen species (ROS) in vitro and suppressed the growth of CRPC tumors in xenograft models. In addition, we reported that BSGWE inhibited STAT3 expression, which partly accounted for the inhibition of the transcription of PD-L1 and led to ferroptosis, manifested by the downregulation of SLC7A11 and GPX4 expression. Furthermore, BSGWE exhibited a synergistic effect with 5-fluorouracil (5-Fu) in chemotherapy of CRPC in vitro and in vivo. This study provides biological evidence that BSGWE is a novel STAT3 inhibitor that exerts anti-proliferation, pro-cell death, and pro-immunity effect and indicates a novel utilization of BSGWE in neoadjuvant chemotherapy of CRPC.http://www.sciencedirect.com/science/article/pii/S1756464624000203Sporoderm-Broken Spores of Ganoderma LucidumSTAT3ImmunityFerroptosisCastration-resistant Prostate CancerAntitumor effect |
| spellingShingle | Xumin Zhou Jiaqi Wang Yufei Guo Houhua Lai Shilong Cheng Zhongjie Chen Hua Li Qiang Li Xiangming Mao Water extract of sporoderm-broken spores of Ganoderma lucidum elicits dual antitumor effects by inhibiting p-STAT3/PD-L1 and promoting ferroptosis in castration-resistant prostate cancer Journal of Functional Foods Sporoderm-Broken Spores of Ganoderma Lucidum STAT3 Immunity Ferroptosis Castration-resistant Prostate Cancer Antitumor effect |
| title | Water extract of sporoderm-broken spores of Ganoderma lucidum elicits dual antitumor effects by inhibiting p-STAT3/PD-L1 and promoting ferroptosis in castration-resistant prostate cancer |
| title_full | Water extract of sporoderm-broken spores of Ganoderma lucidum elicits dual antitumor effects by inhibiting p-STAT3/PD-L1 and promoting ferroptosis in castration-resistant prostate cancer |
| title_fullStr | Water extract of sporoderm-broken spores of Ganoderma lucidum elicits dual antitumor effects by inhibiting p-STAT3/PD-L1 and promoting ferroptosis in castration-resistant prostate cancer |
| title_full_unstemmed | Water extract of sporoderm-broken spores of Ganoderma lucidum elicits dual antitumor effects by inhibiting p-STAT3/PD-L1 and promoting ferroptosis in castration-resistant prostate cancer |
| title_short | Water extract of sporoderm-broken spores of Ganoderma lucidum elicits dual antitumor effects by inhibiting p-STAT3/PD-L1 and promoting ferroptosis in castration-resistant prostate cancer |
| title_sort | water extract of sporoderm broken spores of ganoderma lucidum elicits dual antitumor effects by inhibiting p stat3 pd l1 and promoting ferroptosis in castration resistant prostate cancer |
| topic | Sporoderm-Broken Spores of Ganoderma Lucidum STAT3 Immunity Ferroptosis Castration-resistant Prostate Cancer Antitumor effect |
| url | http://www.sciencedirect.com/science/article/pii/S1756464624000203 |
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