Apoptotic and autophagic death union by Thuja occidentalis homeopathic drug in cervical cancer cells with thujone as the bioactive principle

Pal, Asmita; Das, Subhadeep; Basu, Soumalee; Kundu, Rita

doi:10.1016/j.joim.2022.06.004

Cited by 11 publications

(5 citation statements)

References 32 publications

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Section: Discussionmentioning

confidence: 92%

“…Extending the exploration of natural therapeutics, the study also investigated the major phytoconstituents of thuja for their potential efficacy against BPV-EGFR networks due to their prior reports of clinical efficacy [25][26][27][28]. The focus on alpha-Thujone, beta-Thujone, Fenchone, p-Cymene-8ol, Terpinene-4-ol, and Beyerene provides a nuanced view of the phytochemical composition of Thuja.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive Network and Structural Analysis of Bovine Papillomavirus, Squamous Cell Carcinoma Markers, and Elucidation of Efficacy Mechanisms of Phytochemicals from Thuja Occidentalis

Rahman,

Kumar

2024

Arch Pharmacol Ther

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Papillomaviruses infect cutaneous tissue in various species including bovines and from benign warts to malignant squamous cell carcinoma causing severe economic losses to the farmers. The mechanisms by which bovine papillomaviruses interact with host tissue are unclear. Hence in this study using classical network analysis tools, we evaluated interactions of Bovine papilloma (BPV) variants, with markers and receptors implicated in squamous cell carcinoma. Additionally, the Thuja phytoconstituents were also evaluated for its potential to target the BPV and squamous cell carcinoma network interactions to understand the mechanism of its clinical benefits. Various protein composition of 14 different virus variants of BPV were assessed against 24 markers of squamous cell carcinoma. Among these interactions EGFR consistently exhibited high-affinity interactions with the E1 protein in all isoforms of BPV. Type 4 BPV displayed the maximum number of binding sites (14) with a binding pocket score ranging from 15.47 to 141.34 and a probability score of 0.75 to 0.99. The comparison of the binding pockets identified that BPV types 2 and 13 had the highest number of common amino acid sequences. Further the alpha helix structure of specific common amino acid sequences contributes to a more robust and widespread affinity interaction with both E1 of various BPV types and EGFR. Analysis of Thuja phytochemicals suggested superior efficacy of Beyerene and Terpinene-4-ol towards all ten BPV targets and bEGFR. In conclusion, our comprehensive study leading to identification of E1 protein of BPV as a major interacting network with bEGFR, their key binding sites, and efficacy of Thuja phytoconstituents offer valuable insight into further experimental validation and development of novel therapeutic strategies against BPV-associated diseases.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Comprehensive Network and Structural Analysis of Bovine Papillomavirus, Squamous Cell Carcinoma Markers, and Elucidation of Efficacy Mechanisms of Phytochemicals from Thuja Occidentalis

Rahman,

Kumar

2024

Arch Pharmacol Ther

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“…Extending the exploration of natural therapeutics, the study also investigated the major phytoconstituents of thuja for their potential efficacy against BPV-EGFR networks due to their prior reports of clinical efficacy. [25][26][27][28] The focus on alpha-Thujone, beta-Thujone, Fenchone, p-Cymene-8-ol, Terpinene-4-ol, and Beyerene provides a nuanced view of the phytochemical composition of thuja. Molecular docking studies against key BPV targets and EGFR elucidate the potential of these phytoconstituents in mitigating the pathogenesis of the virus.…”

Section: Discussionmentioning

confidence: 99%

“…The evaluation of thuja phytoconstituents against BPV targets and EGFR, the predominance of alpha-Thujone in the extract underscores its potential as a major contributor to the observed effects. [25-28] The molecular docking studies reveal promising affinities of Beyerene and Terpinene-4-ol against all tested targets, suggesting their potential as key therapeutic components. The distinct affinities of alpha and beta-Thujone against specific BPV types and EGFR, along with the unique characteristics of Fenchone and p-Cymene-8-ol, provide a basis for further investigation into the therapeutic potential of thuja phytoconstituents against BPV-induced conditions.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Network and Structural Analysis of Bovine Papillomavirus, Squamous Cell Carcinoma Markers, and Elucidation of Efficacy Mechanisms of Phytochemicals fromThuja Occidentalis

Rahman,

Kumar

2023

Preprint

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Papillomaviruses infect cutaneous tissue in various species including bovines and from benign warts to malignant squamous cell carcinoma causing severe economic losses to the farmers. The mechanisms by which bovine papillomaviruses interact with host tissue are unclear. Hence in this study using classical network analysis tools, we evaluated interactions of Bovine papilloma (BPV) variants, with markers and receptors implicated in squamous cell carcinoma. Additionally, the thuja phytoconstituents were also evaluated for its potential to target the BPV and squamous cell carcinoma network interactions to understand the mechanism of its clinical benefits. Various protein composition of 14 different virus variants of BPV were assessed against 24 markers of squamous cell carcinoma. Among these interactions EGFR consistently exhibited high-affinity interactions with the E1 protein in all isoforms of BPV. Type 4 BPV displayed the maximum number of binding sites (14) with a binding pocket score ranging from 15.47 to 141.34 and a probability score of 0.75 to 0.99. The comparison of the binding pockets identified that BPV types 2 and 13 had the highest number of common amino acid sequences. Further the alpha helix structure of specific common amino acid sequences, contribute to a more robust and widespread affinity interaction with both E1 of various BPV types and EGFR. Analysis of thuja phytochemicals suggested superior efficacy of Beyerene and Terpinene-4-ol towards all ten BPV targets and bEGFR. In conclusion, our comprehensive study leading to identification of E1 protein of BPV as a major interacting network with bEGFR, their key binding sites, and efficacy of thuja phytoconstituents offer valuable insight into further experimental validation and development of novel therapeutic strategies against BPV-associated diseases.

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“…Consequently, conventional approaches, such as surgery, radiotherapy, and chemotherapy, remain prevalent in clinical practice, despite causing patients considerable physical trauma ( Marnitz et al, 2020 ; Bhatla et al, 2021 ). Thus, researchers continue to explore novel treatments for advanced CC ( Pal et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

GuiErBai: a potent inhibitor, exhibiting broadly antitumor effect against cervical cancer in vitro and in vivo

Qin,

Peng,

et al. 2024

Front. Pharmacol.

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Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated.Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups.Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased (p < 0.001), while the G2/M phase increased notably (p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines (p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated (p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased (p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues.Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo, in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.

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Apoptotic and autophagic death union by Thuja occidentalis homeopathic drug in cervical cancer cells with thujone as the bioactive principle

Cited by 11 publications

References 32 publications

Comprehensive Network and Structural Analysis of Bovine Papillomavirus, Squamous Cell Carcinoma Markers, and Elucidation of Efficacy Mechanisms of Phytochemicals from Thuja Occidentalis

Comprehensive Network and Structural Analysis of Bovine Papillomavirus, Squamous Cell Carcinoma Markers, and Elucidation of Efficacy Mechanisms of Phytochemicals from Thuja Occidentalis

Comprehensive Network and Structural Analysis of Bovine Papillomavirus, Squamous Cell Carcinoma Markers, and Elucidation of Efficacy Mechanisms of Phytochemicals fromThuja Occidentalis

GuiErBai: a potent inhibitor, exhibiting broadly antitumor effect against cervical cancer in vitro and in vivo

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