A pharmacoinformatic approach for studying Atractylodes Lancea DC’s anticancer potential and control ROS-mediated apoptosis against prostate cancer cells
IntroductionProstate cancer (PCa) is a malignancy characterized by abnormal cell proliferation in the prostate gland, a critical component of the male reproductive system. Atractylodes lancea DC. (ALD), a medicinal herb commonly used in traditional Asian medicine, is highly regarded for its antioxid...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1471110/full |
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| author | Chi-Hoon Ahn Ji Soo Myong Kazi Rejvee Ahmed Md Ataur Rahman Md. Maharub Hossain Fahim Min Choi Muntajin Rahman Jinwon Choi Kiryang Kim Seungjoon Moon Seungjoon Moon Mohammed Dalli Mohammed Dalli Rony Abdi Syahputra Sang-Won Shin Abdel Halim Harrath Moon Nyeo Park Bonglee Kim Hwa-Seung Yoo |
| author_facet | Chi-Hoon Ahn Ji Soo Myong Kazi Rejvee Ahmed Md Ataur Rahman Md. Maharub Hossain Fahim Min Choi Muntajin Rahman Jinwon Choi Kiryang Kim Seungjoon Moon Seungjoon Moon Mohammed Dalli Mohammed Dalli Rony Abdi Syahputra Sang-Won Shin Abdel Halim Harrath Moon Nyeo Park Bonglee Kim Hwa-Seung Yoo |
| author_sort | Chi-Hoon Ahn |
| collection | DOAJ |
| description | IntroductionProstate cancer (PCa) is a malignancy characterized by abnormal cell proliferation in the prostate gland, a critical component of the male reproductive system. Atractylodes lancea DC. (ALD), a medicinal herb commonly used in traditional Asian medicine, is highly regarded for its antioxidant, antidiabetic, and anticancer properties. Virtual docking stud-ies have identified Atractylenolide II and III as active components of ALD, demonstrating strong binding potential to inhibit androgen receptor (AR) activity, with docking scores of -8.9 and -9.3, respectively. These findings suggest that ALD may exert a synergistic effect comparable to or greater than that of enzalutamide (ENZ) in inhibiting AR. How-ever, its specific anticancer and anti-metastatic mechanisms in prostate cancer remain unclear.MethodsThe cytotoxic effects of ALD were evaluated on PC3 and DU145 prostate cancer cells, as well as on the normal prostate cell line BPH-1. Cell viability was assessed using the EZ-Cytotoxic kit, while colony formation assays and TUNEL staining were used to meas-ure proliferation and apoptosis, respectively. Apoptosis was further analyzed through an-nexin V-FITC/PI staining and quantified by flow cytometry (FACS). Western blotting was performed to elucidate the underlying molecular mechanisms. Additionally, mito-chondrial membrane potential (ΔΨm) and intracellular calcium levels were measured to evaluate mitochondrial function, while reactive oxygen species (ROS) generation was assessed with and without pretreatment with N-acetylcysteine (NAC) .ResultsALD selectively reduced the viability of PC3 and DU145 prostate cancer cells while spar-ing BPH-1 normal prostate cells, demonstrating cancer-selective cytotoxicity. ALD dis-rupted mitochondrial function by reducing ΔΨm and increasing intracellular calcium lev-els. A concentration-dependent increase in ROS generation was observed in PC3 and DU145 cells, which was completely inhibited by NAC pretreatment, confirming a ROS-mediated mechanism. Colony formation assays revealed a significant reduction in prolif-eration, while TUNEL and annexin V-FITC/PI staining indicated enhanced apoptosis. Western blot analysis showed that ALD modulates critical survival pathways, leading to apoptotic cell death.DiscussionThese findings demonstrate that ALD exerts potent anticancer effects against metastatic prostate cancer cells through ROS-mediated apoptosis and mitochondrial dysfunction, while exhibiting minimal cytotoxicity toward normal prostate cells. The presence of ac-tive compounds such as Atractylenolide II and III suggests a synergistic interaction that enhances AR inhibition and promotes apoptosis. ALD’s ability to engage multiple path-ways highlights its therapeutic potential as a selective and multifaceted treatment for ag-gressive prostate cancer. |
| format | Article |
| id | doaj-art-0f712add1c124a6c89c82705b96d27fb |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-0f712add1c124a6c89c82705b96d27fb2025-02-05T07:32:10ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-02-011510.3389/fonc.2025.14711101471110A pharmacoinformatic approach for studying Atractylodes Lancea DC’s anticancer potential and control ROS-mediated apoptosis against prostate cancer cellsChi-Hoon Ahn0Ji Soo Myong1Kazi Rejvee Ahmed2Md Ataur Rahman3Md. Maharub Hossain Fahim4Min Choi5Muntajin Rahman6Jinwon Choi7Kiryang Kim8Seungjoon Moon9Seungjoon Moon10Mohammed Dalli11Mohammed Dalli12Rony Abdi Syahputra13Sang-Won Shin14Abdel Halim Harrath15Moon Nyeo Park16Bonglee Kim17Hwa-Seung Yoo18College of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaEast West Cancer Center, Seoul Korean Medicine Hospital, Daejeon University, Seoul, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaDepartment of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, United StatesCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaChansol Hospital of Korean Medicine, Incheon, Republic of KoreaLaboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed the First, Oujda, MoroccoHigher Institute of Nursing Professions and Health Techniques, Oujda, MoroccoDepartment of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, Sumatera Utara, IndonesiaDepartment of Humanities & Social Medicine, School of Korean Medicine, Pusan National University, Yangsan-si, Gyeongsangnam-do, Republic of KoreaCollege of Science, Department of Zoology, King Saud University, Riyadh, Saudi ArabiaCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaEast West Cancer Center, Seoul Korean Medicine Hospital, Daejeon University, Seoul, Republic of KoreaIntroductionProstate cancer (PCa) is a malignancy characterized by abnormal cell proliferation in the prostate gland, a critical component of the male reproductive system. Atractylodes lancea DC. (ALD), a medicinal herb commonly used in traditional Asian medicine, is highly regarded for its antioxidant, antidiabetic, and anticancer properties. Virtual docking stud-ies have identified Atractylenolide II and III as active components of ALD, demonstrating strong binding potential to inhibit androgen receptor (AR) activity, with docking scores of -8.9 and -9.3, respectively. These findings suggest that ALD may exert a synergistic effect comparable to or greater than that of enzalutamide (ENZ) in inhibiting AR. How-ever, its specific anticancer and anti-metastatic mechanisms in prostate cancer remain unclear.MethodsThe cytotoxic effects of ALD were evaluated on PC3 and DU145 prostate cancer cells, as well as on the normal prostate cell line BPH-1. Cell viability was assessed using the EZ-Cytotoxic kit, while colony formation assays and TUNEL staining were used to meas-ure proliferation and apoptosis, respectively. Apoptosis was further analyzed through an-nexin V-FITC/PI staining and quantified by flow cytometry (FACS). Western blotting was performed to elucidate the underlying molecular mechanisms. Additionally, mito-chondrial membrane potential (ΔΨm) and intracellular calcium levels were measured to evaluate mitochondrial function, while reactive oxygen species (ROS) generation was assessed with and without pretreatment with N-acetylcysteine (NAC) .ResultsALD selectively reduced the viability of PC3 and DU145 prostate cancer cells while spar-ing BPH-1 normal prostate cells, demonstrating cancer-selective cytotoxicity. ALD dis-rupted mitochondrial function by reducing ΔΨm and increasing intracellular calcium lev-els. A concentration-dependent increase in ROS generation was observed in PC3 and DU145 cells, which was completely inhibited by NAC pretreatment, confirming a ROS-mediated mechanism. Colony formation assays revealed a significant reduction in prolif-eration, while TUNEL and annexin V-FITC/PI staining indicated enhanced apoptosis. Western blot analysis showed that ALD modulates critical survival pathways, leading to apoptotic cell death.DiscussionThese findings demonstrate that ALD exerts potent anticancer effects against metastatic prostate cancer cells through ROS-mediated apoptosis and mitochondrial dysfunction, while exhibiting minimal cytotoxicity toward normal prostate cells. The presence of ac-tive compounds such as Atractylenolide II and III suggests a synergistic interaction that enhances AR inhibition and promotes apoptosis. ALD’s ability to engage multiple path-ways highlights its therapeutic potential as a selective and multifaceted treatment for ag-gressive prostate cancer.https://www.frontiersin.org/articles/10.3389/fonc.2025.1471110/fullAtractylodes lancea DC.prostate cancerreactive oxygen speciesapoptosismitochondrial membrane potential |
| spellingShingle | Chi-Hoon Ahn Ji Soo Myong Kazi Rejvee Ahmed Md Ataur Rahman Md. Maharub Hossain Fahim Min Choi Muntajin Rahman Jinwon Choi Kiryang Kim Seungjoon Moon Seungjoon Moon Mohammed Dalli Mohammed Dalli Rony Abdi Syahputra Sang-Won Shin Abdel Halim Harrath Moon Nyeo Park Bonglee Kim Hwa-Seung Yoo A pharmacoinformatic approach for studying Atractylodes Lancea DC’s anticancer potential and control ROS-mediated apoptosis against prostate cancer cells Frontiers in Oncology Atractylodes lancea DC. prostate cancer reactive oxygen species apoptosis mitochondrial membrane potential |
| title | A pharmacoinformatic approach for studying Atractylodes Lancea DC’s anticancer potential and control ROS-mediated apoptosis against prostate cancer cells |
| title_full | A pharmacoinformatic approach for studying Atractylodes Lancea DC’s anticancer potential and control ROS-mediated apoptosis against prostate cancer cells |
| title_fullStr | A pharmacoinformatic approach for studying Atractylodes Lancea DC’s anticancer potential and control ROS-mediated apoptosis against prostate cancer cells |
| title_full_unstemmed | A pharmacoinformatic approach for studying Atractylodes Lancea DC’s anticancer potential and control ROS-mediated apoptosis against prostate cancer cells |
| title_short | A pharmacoinformatic approach for studying Atractylodes Lancea DC’s anticancer potential and control ROS-mediated apoptosis against prostate cancer cells |
| title_sort | pharmacoinformatic approach for studying atractylodes lancea dc s anticancer potential and control ros mediated apoptosis against prostate cancer cells |
| topic | Atractylodes lancea DC. prostate cancer reactive oxygen species apoptosis mitochondrial membrane potential |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1471110/full |
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