Terpinen-4-ol inhibits the proliferation and mobility of pancreatic cancer cells by downregulating Rho-associated coiled-coil containing protein kinase 2

Cao, Wenpeng; Tian, Ruhua; Pan, Runsang; Sun, Baofei; Xiao, Chaolun; Chen, Yunhua; Zeng, Zhirui; Lei, Shan

doi:10.1080/21655979.2022.2054205

Cited by 12 publications

(11 citation statements)

References 41 publications

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“…RNA sequencing further identified Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) as the potential target of T-4-ol as it lowers its cellular levels in AsPC-1 and PANC-1 cells. These results were also validated in a subcutaneous tumorigenic model (BALB/c nude mice) where intraperitoneal injection of T-4-ol (40 mg/kg body weight, every 5 days) lowered tumor growth/progression and size accompanied by decreased expression of ROCK2 and epithelial-mesenchymal transition markers (PCNA, Ki-67, N-cadherin, and vimentin) [78]. In the subsequent study, Cao et al showed that the proliferation of LN229, T98, and U251 glioma cell lines is adversely affected by T-4-ol (1-4 μM) treatment [79].…”

Section: Anti-cancer Activity Of T-4-ol: Combating a Devastating Diseasementioning

confidence: 60%

“…Recent investigations led by Cao and colleagues have also indicated the wide-spectrum anti-cancer potential of T-4-ol in effectively curtailing pancreatic cancer [78] and glioma [79]. The authors reported that T-4-ol (1-4 μM) significantly inhibited cellular proliferation, lowered cell migration and invasion (malignant phenotype) of AsPC-1 and PANC-1 pancreatic cell lines in vitro along with inducing apoptosis through increased caspase 3 cleavage and reduced Bcl-2 protein levels [78]. RNA sequencing further identified Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) as the potential target of T-4-ol as it lowers its cellular levels in AsPC-1 and PANC-1 cells.…”

Section: Anti-cancer Activity Of T-4-ol: Combating a Devastating Diseasementioning

confidence: 99%

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A Comprehensive Review on the Pharmacological Prospects of Terpinen-4-Ol: From Nature to Medicine and Beyond

Prerna,

Chadha,

Khullar

et al. 2024

Preprint

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Owing to their extensive biological potential, essential oils (EOs) and their bioactive phytochemicals have gained attention from the scientific community. Within this domain, Terpinen-4-ol (T-4-ol), a bioactive monoterpene alcohol and the major constituent of tea tree oil (TTO), has made its way into translational research. Recent literature on T-4-ol strongly indicates its diverse pharmacological properties, including but not limited to antimicrobial, antivirulent, antioxidant, anti-inflammatory, anti-hypertensive, and anti-cancer effects. Hence, this review provides a comprehensive overview of the multifaceted biological activities exhibited by T-4-ol, emphasizing its medicinal potential for widescale application. The antibacterial and antifungal effectiveness of T-4-ol has been discussed encompassing its role in combating a broad spectrum of bacterial and fungal pathogens, respectively. The review delves into the antivirulent prospects of T-4-ol, shedding light on its ability to attenuate virulence and mitigate bacterial pathogenesis. Scientific literature on the antioxidant and anti-inflammatory activity of T-4-ol highlighting its role in neutralizing reactive oxygen species and modulating inflammatory pathways has also been collated. Furthermore, the review elaborates on the cardioprotective and anti-hypertensive properties of T-4-ol and augments literature on its anti-cancer mechanism against various cancer cell lines. Overall, this review consolidates the existing knowledge on T-4-ol, providing a holistic understanding of its pharmacological abilities. The exploration of these diverse attributes positions T-4-ol as a promising candidate for further research and therapeutic repurposing in various biomedical applications.

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Section: Anti-cancer Activity Of T-4-ol: Combating a Devastating Diseasementioning

confidence: 60%

Section: Anti-cancer Activity Of T-4-ol: Combating a Devastating Diseasementioning

confidence: 99%

A Comprehensive Review on the Pharmacological Prospects of Terpinen-4-Ol: From Nature to Medicine and Beyond

Prerna,

Chadha,

Khullar

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…After high-quality clean reads were obtained and batch normalization was performed, the count data were analyzed using the EdgeR package. P values < 0.05 and |LogFold-Change| values ≥2 were used as test criteria for differentially expressed genes [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Ar-turmerone inhibits the proliferation and mobility of glioma by downregulating cathepsin B

Cao,

Chen,

Xiao

et al. 2023

Aging

Self Cite

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Ar-turmerone, a compound isolated from turmeric seeds, has exhibited anti-malignant, anti-aging and anti-inflammatory properties. Here, we assessed the effects of ar-turmerone on glioma cells. U251, U87 and LN229 glioma cell lines were treated with different concentrations of ar-turmerone (0, 50, 100 and 200 μM), and their viability and mobility were evaluated using Cell Counting Kit 8, colony formation, wound healing and Transwell assays. The effects of ar-turmerone on U251 glioma cell proliferation were also assessed using a subcutaneous implantation tumor model. High-throughput sequencing, bioinformatic analyses and quantitative real-time polymerase chain reactions were used to identify the key signaling pathways and targets of ar-turmerone. Ar-turmerone reduced the proliferation rate and mobility of glioma cells in vitro and arrested cell division at G1/S phase. Cathepsin B was identified as a key target of ar-turmerone in glioma cells. Ar-turmerone treatment reduced cathepsin B expression and inhibited the cleavage of its target protein P27 in glioma cells. On the other hand, cathepsin B overexpression reversed the inhibitory effects of ar-turmerone on glioma cell proliferation, mobility progression in vitro and in vivo . In conclusion, ar-turmerone suppressed cathepsin B expression and P27 cleavage, thereby inhibiting the proliferation and mobility of glioma cells.

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“…Medicinal plants are a huge source for drug discovery, and numerous studies have shown that plant extracts have anti-proliferative or anti-tumor effects on tumor cells [ 5 ]. Terpinen-4-ol (T4O) has anti-tumor, anti-bacterial, anti-fungal, anti-platelet, anti-oxidation, anti-senile dementia, and anti-metabolic syndrome properties [ 6 ]. Ken et al reported that T4O inhibits colorectal cancer growth by increasing the levels of reactive oxygen species [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Ken et al reported that T4O inhibits colorectal cancer growth by increasing the levels of reactive oxygen species [ 7 ]. Furthermore, Cao et al have shown that terpine-4-ol inhibits the proliferation of pancreatic cancer cells by downregulating the Rho-associated coiled-coil protein kinase 2 [ 6 ]. However, the effects of T4O and its underlying mechanisms on gliomas have not yet been clarified.…”

Section: Introductionmentioning

confidence: 99%

Terpinen-4-ol Induces Ferroptosis of Glioma Cells via Downregulating JUN Proto-Oncogene

Cao

Zeng

et al. 2023

Molecules

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According to previous research, turmeric seeds exhibit anti-inflammatory, anti-malignancy, and anti-aging properties due to an abundance of terpinen-4-ol (T4O). Although it is still unclear how T4O works on glioma cells, limited data exist regarding its specific effects. In order to determine whether or not glioma cell lines U251, U87, and LN229 are viable, CCK8 was used as an assay and a colony formation assay was performed using different concentrations of T4O (0, 1, 2, and 4 μM). The effect of T4O on the proliferation of glioma cell line U251 was detected through the subcutaneous implantation of the tumor model. Through high-throughput sequencing, a bioinformatic analysis, and real-time quantitative polymerase chain reactions, we identified the key signaling pathways and targets of T4O. Finally, for the measurement of the cellular ferroptosis levels, we examined the relationship between T4O, ferroptosis, and JUN and the malignant biological properties of glioma cells. T4O significantly inhibited glioma cell growth and colony formation and induced ferroptosis in the glioma cells. T4O inhibited the subcutaneous tumor proliferation of the glioma cells in vivo. T4O suppressed JUN transcription and significantly reduced its expression in the glioma cells. The T4O treatment inhibited GPX4 transcription through JUN. The overexpression of JUN suppressed ferroptosis in the cells rescued through T4O treatment. Taken together, our data suggest that the natural product T4O exerts its anti-cancer effects by inducing JUN/GPX4-dependent ferroptosis and inhibiting cell proliferation, and T4O will hope-fully serve as a prospective compound for glioma treatment.

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Terpinen-4-ol inhibits the proliferation and mobility of pancreatic cancer cells by downregulating Rho-associated coiled-coil containing protein kinase 2

Cited by 12 publications

References 41 publications

A Comprehensive Review on the Pharmacological Prospects of Terpinen-4-Ol: From Nature to Medicine and Beyond

A Comprehensive Review on the Pharmacological Prospects of Terpinen-4-Ol: From Nature to Medicine and Beyond

Ar-turmerone inhibits the proliferation and mobility of glioma by downregulating cathepsin B

Terpinen-4-ol Induces Ferroptosis of Glioma Cells via Downregulating JUN Proto-Oncogene

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