Enhancing effect of natural borneol on the cellular uptake of demethoxycurcumin and their combined induction of G2/M arrest in HepG2 cells via ROS generation

Chen, Jianping; Lin, Li; Su, Jianyu; Li, Bing; Chen, Tianfeng; Ling, Fengqing; Zhang, Xia

doi:10.1016/j.jff.2015.05.013

Cited by 10 publications

(5 citation statements)

References 49 publications

(38 reference statements)

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“…The SPRi-MS results reveal that ABCB5 and MDR3 are captured by NB, which further supports this hypothesis. Previously, we found that NB could synergize with selenocystine, curcumin, and bisdemethoxycurcumin to induce significant anticancer activities 18 - 20 . However, the exact mechanisms and the therapeutic target of NB remained elusive.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence shows that NB can promote the transdermal and mucosal absorption of drugs 16 , 17 . Recently, NB has been shown to enhance the anti-tumor effects of selenocysteine 18 , curcumin 19 , didemethoxycurcumin 20 , cisplatin 21 , and paclitaxel 6 . Although these studies suggest the potential application of NB in cancer prevention, it is not clear whether NB can be used to improve the therapeutic efficiency of chemotherapy in lung cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

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TRPM8-regulated calcium mobilization plays a critical role in synergistic chemosensitization of Borneol on Doxorubicin

Lai¹,

Liu²,

Hou³

et al. 2020

Theranostics

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Background: Lung cancer has a high mortality rate and is resistant to multiple chemotherapeutics. Natural Borneol (NB) is a monoterpenoid compound that facilitates the bioavailability of drugs. In this study, we investigated the effects of NB on chemosensitivity in the A549 human lung adenocarcinoma cell line and to elucidate therapeutic molecular target of NB. Methods: The chemosensitivity effects of NB in A549 cells were examined by MTT assay. The mechanism of NB action was evaluated using flow cytometry and Western blotting assays. Surface plasmon resonance (SPR) and LC-MS combined analysis (MS-SPRi) was performed to elucidate the candidate molecular target of NB. The chemosensitizing capacity of NB in vivo was assessed in nude mice bearing A549 tumors. Results: NB pretreatment sensitized A549 cells to low doxorubicin (DOX) dosage, leading to a 15.7% to 41.5% increase in apoptosis. This increase was correlated with ERK and AKT inactivation and activation of phospho-p38 MAPK, phospho-JNK, and phosphor-p53. Furthermore, this synergism depends on reactive oxygen species (ROS) generation. MS-SPRi analysis revealed that transient receptor potential melastatin-8 (TRPM8) is the candidate target of NB in potentiating DOX killing potency. Genetically, TRPM8 knock-down significantly suppresses the chemosensitizing effects of NB and inhibits ROS generation through restraining calcium mobilization. Moreover, pretreatment with NB synergistically enhances the anticancer effects of DOX to delay tumor progression in vivo . Conclusions: These results suggest that TRPM8 may be a valid therapeutic target in the potential application of NB, and show that NB is a chemosensitizer for lung cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TRPM8-regulated calcium mobilization plays a critical role in synergistic chemosensitization of Borneol on Doxorubicin

Lai¹,

Liu²,

Hou³

et al. 2020

Theranostics

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“…In most cancer cells, the Akt signaling pathway also plays an important role in the G2/M phase and in apoptosis and survival [71]. Chen et al (2015) found that flavin compounds can induce G2/M phase arrest in cells by regulating the Akt pathway [72]. In addition, inhibition of Akt activation can also inhibit cancer cell migration by upregulating E-calmodulin, β-linked protein and downregulating the mesenchymal cell waveform protein [73,74].…”

Section: Screening By Molecular Docking Simulationmentioning

confidence: 99%

Regulation of Tumor Apoptosis of Poriae cutis-Derived Lanostane Triterpenes by AKT/PI3K and MAPK Signaling Pathways In Vitro

Yue,

Feng,

Cai

et al. 2023

Nutrients

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Poria cocos is traditionally used as both food and medicine. Triterpenoids in Poria cocos have a wide range of pharmacological activities, such as diuretic, sedative and tonic properties. In this study, the anti-tumor activities of poricoic acid A (PAA) and poricoic acid B (PAB), purified by high-speed counter-current chromatography, as well as their mechanisms and signaling pathways, were investigated using a HepG2 cell model. After treatment with PAA and PAB on HepG2 cells, the apoptosis was obviously increased (p < 0.05), and the cell cycle arrested in the G2/M phase. Studies showed that PAA and PAB can also inhibit the occurrence and development of tumor cells by stimulating the generation of ROS in tumor cells and inhibiting tumor migration and invasion. Combined Polymerase Chain Reaction and computer simulation of molecular docking were employed to explore the mechanism of tumor proliferation inhibition by PAA and PAB. By interfering with phosphatidylinositol-3-kinase/protein kinase B, Mitogen-activated protein kinases and p53 signaling pathways; and further affecting the expression of downstream caspases; matrix metalloproteinase family, cyclin-dependent kinase -cyclin, Intercellular adhesion molecules-1, Vascular Cell Adhesion Molecule-1 and Cyclooxygenase -2, may be responsible for their anti-tumor activity. Overall, the results suggested that PAA and PAB induced apoptosis, halted the cell cycle, and inhibited tumor migration and invasion through multi-pathway interactions, which may serve as a potential therapeutic agent against cancer.

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“…Nowadays, accumulating studies have shown that borneol can promote the transdermal and mucosal absorption of drugs. Recently, some studies disclosed that borneol can enhance the anti-tumor effects of selenocysteine [17], curcumin [18], didemethoxycurcumin [19], cisplatin [20] and paclitaxel [9]. Although these studies have suggested the 4 potential application prospect of borneol in cancer prevention, it is not clear whether borneol can be used to improve the therapeutic efficiency of chemotherapy in lung cancer treatment, and the candidate target of borneol in chemotherapy is remain to be authenticated.…”

Section: Introductionmentioning

confidence: 99%

Chemosensitization of doxorubicin against lung cancer by nature borneol, involvement of TRPM8-regulated calcium mobilization

Lai¹,

Liu

Lin³

et al. 2020

Preprint

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Background Lung cancer possesses high mortality rate and tolerances to multiple chemotherapeutics. Natural Borneol (NB) is a monoterpenoid compound that found to facilitate the bioavailability of drugs. In this study, we attempted to investigate effects of NB on the chemosensitivity in A549 cells and try to elucidate its therapeutic target. Methods The effects of NB on chemosensitivity in A549 cells was examined by MTT assay. The mechanism studies were evaluated by flow cytometry and western blotting assay. Surface plasmon resonance (SPR) and LC-MS combined analysis (MS-SPRi) was performed to elucidate the candidate target of NB contributes to this synergism. The chemosensitizing capacity of NB in vivo was conducted in nude mice bearing A549 tumors. Results NB pretreatment sensitizes A549 cells to low dosage of DOX, leading to a 15.7% to 41.5% increase in apoptosis, which is corelated with ERK and AKT inactivation but activation of phosphor-p38MAPK, -JNK and p53. Furthermore, this synergism depends on reactive oxygen species (ROS) generation. The MS-SPRi analysis reveals that the transient receptor potential melastatin-8 (TRPM8) is the interaction target of NB in potentiating DOX killing potency. Genetically knock down of TRPM8 significantly suppress the chemosensitizing effects of NB with the involvement of inhibiting ROS generation through restraining calcium mobilization. Moreover, pretreatment of NB synergistically enhanced the anticancer effects of DOX to delay tumor progression in vivo. Conclusions These results suggest that TRPM8 may be a valid therapeutic target in the potential application of NB serves as a chemosensitizer for lung cancer treatment.

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Enhancing effect of natural borneol on the cellular uptake of demethoxycurcumin and their combined induction of G2/M arrest in HepG2 cells via ROS generation

Cited by 10 publications

References 49 publications

TRPM8-regulated calcium mobilization plays a critical role in synergistic chemosensitization of Borneol on Doxorubicin

TRPM8-regulated calcium mobilization plays a critical role in synergistic chemosensitization of Borneol on Doxorubicin

Regulation of Tumor Apoptosis of Poriae cutis-Derived Lanostane Triterpenes by AKT/PI3K and MAPK Signaling Pathways In Vitro

Chemosensitization of doxorubicin against lung cancer by nature borneol, involvement of TRPM8-regulated calcium mobilization

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