Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways

Yang, Chengsheng; Mai, Zhikai; Liu, Can; Yin, Shuanghong; Cai, Yun; Xia, Chenglai

doi:10.3390/molecules27113513

Cited by 13 publications

(8 citation statements)

References 211 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neovasculature has previously been reported to be governed by different mechanisms, mainly including the induction of EC apoptosis [ 44 ], inhibition of EC remodeling [ 38 ], or chemorepulsion of EC [ 45 ]. Observation of abnormal nucleus structures and apoptotic-like morphology in HUVECs treated with a high dose of BA (10 μ M) reminded us that BA might induce EC death via activating the apoptosis signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Brevilin A Inhibits VEGF-Induced Angiogenesis through ROS-Dependent Mitochondrial Dysfunction

Wei

Hao

Zheng

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Brevilin A (BA), a sesquiterpene lactone isolated from Centipeda minima herb, has been identified to exhibit potent anticancer activity. However, the potential pharmacological effect and mechanism of BA in regulating endothelial cell (EC) angiogenesis, a key event in tumor growth, is poorly understood. In this study, BA was shown to significantly prevent vascular endothelial growth factor (VEGF) induced EC angiogenic capacities in vitro, ex vivo, and in vivo. Subsequent functional assays revealed that BA dose dependently inhibited VEGF-stimulated survival, proliferation, migration, and triggered apoptosis activity in human umbilical vein endothelial cells (HUVECs), as well as suppressed the expression of antiapoptotic protein Bcl-2, increased the expression of proapoptotic protein caspase-3 and Bax, and suppressed PI3K/AKT pathway. Meanwhile, BA was also able to depolarize mitochondrial membranal permeability (MMP), accelerate mitochondrial superoxide accumulation, induce intracellular reactive oxygen species (ROS) production, and decreased intracellular glutathione (GSH) in HUVECs. Furthermore, both mitochondria-specific superoxide scavenger Mito-TEMPOL and broad-spectrum antioxidant N-acetyl-cysteine (NAC) dramatically abolished BA-induced mitochondrial dysfunction and mitochondrial ROS production, causing the reversion of PI3K/AKT pathway and repression of apoptosis, eventually correcting the impaired endothelial behavior in survival, growth, migration, and angiogenesis. Collectively, our data for the first time identified a new mechanism for antiangiogenic effect of BA in vascular EC, one that is based on the regulation of mitochondrial-dependent ROS overproduction.

show abstract

Section: Discussionmentioning

confidence: 99%

Brevilin A Inhibits VEGF-Induced Angiogenesis through ROS-Dependent Mitochondrial Dysfunction

Wei

Hao

Zheng

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…The main routes of resistance in tumors include the Renin-angiotensin system (Ras), Phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), Epidermal growth factor receptor (EGFR), Transforming growth factor-beta (TGF-β), Notch, and Wnt signal pathways ( 222 ). Exploiting natural products that have an inhibitory effect on carcinogenic or cancer-promoting signal pathways is one of strategies to prevent drug resistance in cancer treatment.…”

Section: Natural Products Regulate the Tumor Microenvironment To Over...mentioning

confidence: 99%

Remodeling tumor microenvironment with natural products to overcome drug resistance

Zhang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

With cancer incidence rates continuing to increase and occurrence of resistance in drug treatment, there is a pressing demand to find safer and more effective anticancer strategy for cancer patients. Natural products, have the advantage of low toxicity and multiple action targets, are always used in the treatment of cancer prevention in early stage and cancer supplement in late stage. Tumor microenvironment is necessary for cancer cells to survive and progression, and immune activation is a vital means for the tumor microenvironment to eliminate cancer cells. A number of studies have found that various natural products could target and regulate immune cells such as T cells, macrophages, mast cells as well as inflammatory cytokines in the tumor microenvironment. Natural products tuning the tumor microenvironment via various mechanisms to activate the immune response have immeasurable potential for cancer immunotherapy. In this review, it highlights the research findings related to natural products regulating immune responses against cancer, especially reveals the possibility of utilizing natural products to remodel the tumor microenvironment to overcome drug resistance.

show abstract

“…Among surgery and radiation treatment modalities, chemotherapy remains the modality of choice for cancer therapy, particularly in patients with advanced stages of the disease [ 1 , 2 , 3 ]. However, the use of chemotherapeutic agents for cancer therapy is hindered because of severe long-term side effects and the development of drug resistance caused by inactivation and drug metabolism by different enzymes such as cytochromes P450 [ 4 , 5 , 6 , 7 , 8 , 9 ]. These factors limit the use of chemotherapeutic agents, making it a significant challenge in cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Phytochemical Analysis and Profiling of Antitumor Compounds of Leaves and Stems of Calystegia silvatica (Kit.) Griseb.

2023

View full text Add to dashboard Cite

Anti-tumor compounds from natural products are being investigated as possible alternatives for cancer chemotherapeutics that have serious adverse effects and tumor resistance. Calystegia silvatica was collected from the north coast of Egypt and extracted via methanol and n-hexane sub-fraction. The biologically active compounds of Calystegia silvatica were identified from the methanol and n-hexane extracts from the leaves and stems of the plant using GC-MS and HPLC. The antitumor properties of both parts of the plant were investigated against cancer and non-cancer cell lines using the MTT assay, and the IC50 in comparison to doxorubicin was calculated. The main compounds identified in the methanol extract were cis-vaccenic acid and trans-13-octadecenoic acid in the leaves and stems, respectively, and phenyl undecane and 3,7,11,15 tetramethyl-2-hexadeca-1-ol in the n-hexane extracts of the leaves and stems, respectively. Both parts of the plant contained fatty acids that have potential antitumor properties. The methanol extract from the stems of C. silvatica showed antitumor properties against HeLa, with an IC50 of 114 ± 5 μg/mL, PC3 with an IC50 of 137 ± 18 μg/mL and MCF7 with an IC50 of 172 ± 15 μg/mL, which were greater than Caco2, which had an IC50 of 353 ± 19 μg/mL, and HepG2, which had an IC50 of 236 ± 17 μg/mL. However, the leaf extract showed weak antitumor properties against all of the studied cancer cell lines (HeLa with an IC50 of 208 ± 13 μg/mL, PC3 with an IC50 of 336 ± 57 μg/mL, MCF7 with an IC50 of 324 ± 17 μg/mL, Caco2 with an IC50 of 682 ± 55 μg/mL and HepG2 with an IC50 of 593 ± 22 μg/mL). Neither part of the plant extract showed any cytotoxicity to the normal cells (WI38). Therefore, C. silvatica stems may potentially be used for the treatment of cervical, prostate and breast cancer.

show abstract

Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways

Cited by 13 publications

References 211 publications

Brevilin A Inhibits VEGF-Induced Angiogenesis through ROS-Dependent Mitochondrial Dysfunction

Brevilin A Inhibits VEGF-Induced Angiogenesis through ROS-Dependent Mitochondrial Dysfunction

Remodeling tumor microenvironment with natural products to overcome drug resistance

Phytochemical Analysis and Profiling of Antitumor Compounds of Leaves and Stems of Calystegia silvatica (Kit.) Griseb.

Contact Info

Product

Resources

About