Helicteric Acid, Oleanic Acid, and Betulinic Acid, Three Triterpenes from <i>Helicteres angustifolia</i> L., Inhibit Proliferation and Induce Apoptosis in HT‐29 Colorectal Cancer Cells via Suppressing NF‐<i>κ</i>B and STAT3 Signaling

Su, Dan; Gao, Yuchen; Dai, Weibo; Hu, Ying; Wu, Yanfen; Quanxi, Mei

doi:10.1155/2017/5180707

Cited by 25 publications

(15 citation statements)

References 44 publications

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“…Recent studies have demonstrated that certain natural therapeutic agents serve an inhibitory role in the genesis, progression and metastasis of various cancer types (37). Betulinic acid, a pentacyclic triterpene, extracted from Zizyphus mauritiana, displayed potency in inhibiting STAT-3 activation, Src kinase, and JAK-1 and -2 (124,125). Furthermore, it has been reported that betulinic acid induces apoptosis in thyroid, breast, lung and colon carcinomas, indicating its potential as a chemotherapeutic agent (124).…”

Section: Advances In Antitumor Therapeutics Targeting Stat-3mentioning

confidence: 99%

Overview of the STAT‑3 signaling pathway in cancer and the development of specific inhibitors (Review)

Mohammad

Liu

2020

Oncol Lett

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Signal transducer and activator of transcription (STAT) proteins represent novel therapeutic targets for the treatment of cancer. In particular, STAT-3 serves critical roles in several cellular processes, including the cell cycle, cell proliferation, cellular apoptosis and tumorigenesis. Persistent activation of STAT-3 has been reported in a variety of cancer types, and a poor prognosis of cancer may be associated with the phosphorylation level of STAT-3. Furthermore, elevated STAT-3 activity has been demonstrated in a variety of mammalian cancers, both in vitro and in vivo. This indicates that STAT-3 serves an important role in the progression of numerous cancer types. A significant obstacle in developing STAT-3 inhibitors is the demonstration of the antitumor efficacy in in vivo systems and the lack of animal models for human tumors. Therefore, it is crucial to determine whether available STAT-3 inhibitors are suitable for clinical trials. Moreover, further preclinical studies are necessary to focus on the impact of STAT-3 inhibitors on tumor cells. When considering STAT-3 hyper-activation in human cancer, selective targeting to these proteins holds promise for significant advancement in cancer treatment. In the present study, advances in our knowledge of the structure of STAT-3 protein and its regulatory mechanisms are summarized. Moreover, the STAT-3 signaling pathway and its critical role in malignancy are discussed, in addition to the development of STAT-3 inhibitors in various cancer types. Contents 1. Introduction 2. STAT-3 structure 3. STAT-3 signal transduction cascade 4. Target genes regulated by STAT-3 5. Advances in antitumor therapeutics targeting STAT-3 6. Conclusions

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Section: Advances In Antitumor Therapeutics Targeting Stat-3mentioning

confidence: 99%

Overview of the STAT‑3 signaling pathway in cancer and the development of specific inhibitors (Review)

Mohammad

Liu

2020

Oncol Lett

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“…Both oleanic acid (OA) and ursolic acid (UA) are two representative triterpenoids with certain solubility in water, methanol, ethanol, 2-propanol, and ethyl acetate [ 29 , 30 , 31 , 32 ]. These two compounds have been evidenced to exhibit a variety of activities, including stabilizing liposomal membranes [ 33 ], anti-cancer [ 34 ], anti-diabetes [ 35 , 36 ], anti-inflammation [ 37 ], anti-oxidation [ 2 ], anti-osteoporosis [ 38 , 39 ], etc. In addition, OA is the most abundant potent triterpenoid in FLL with a content ranging from 7.37 to 13.3 mg/g [ 40 ].…”

Section: Phytochemistry Of Fructus Ligustri Lucidimentioning

confidence: 99%

Fructus Ligustri Lucidi in Osteoporosis: A Review of its Pharmacology, Phytochemistry, Pharmacokinetics and Safety

et al. 2017

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Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, pharmacokinetics, pharmacology in bone improving effect, and safety. Materials and Methods: Several databases, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science were consulted to locate publications pertaining to FLL. The initial inquiry was conducted for the presence of the following keywords combinations in the abstracts: Fructus Ligustri Lucidi, osteoporosis, phytochemistry, pharmacokinetics, pharmacology, osteoblasts, osteoclasts, salidroside. About 150 research papers and reviews were consulted. Results: FLL is assumed to exhibit anti-osteoporotic effects by improving liver and kidney deficiencies and reducing lower back soreness in Traditional Chinese Medicine (TCM). The data from animal and cell experiments demonstrate that FLL is able to improve bone metabolism and bone quality in ovariectomized, growing, aged and diabetic rats through the regulation of PTH/FGF-23/1,25-(OH)2D3/CaSR, Nox4/ROS/NF-κB, and OPG/RANKL/cathepsin K signaling pathways. More than 100 individual compounds have been isolated from this plant. Oleanolic acid, ursolic acid, salidroside, and nuzhenide have been reported to exhibit the anti-osteoporosis effect. The pharmacokinetics data reveals that salidroside is one of the active constituents, and that tyrosol is hard to detect under physiological conditions. Acute and subacute toxicity studies show that FLL is well tolerated and presents no safety concerns. Conclusions: FLL provides a new option for the prevention and treatment of osteoporosis, which attracts rising interests in identifying potential anti-osteoporotic compounds and fractions from this plant. Further scientific evidences are expected from well-designed clinical trials on its bone protective effects and safety.

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“… 12 , 19 In CRC cells, BA could induce apoptosis through the mitochondrial pathway, 20 inhibited cell growth of CRC cells by downregulating Sp transcription factors in SW480 and RKO cells, 21 or by suppressing NF- κ B and STAT3 signaling in HT29 cells. 22 It has also been reported that BA can function as NF- κ B activator in a number of other cancer cell lines, 23 suggesting that the antitumor mechanisms of BA was dependent on tumor type.…”

mentioning

confidence: 95%

Overaccumulation of p53-mediated autophagy protects against betulinic acid-induced apoptotic cell death in colorectal cancer cells

Wang

Zhang

et al. 2017

Cell Death Dis

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Betulinic acid (BA) exhibits cytotoxic activity against some cancer cells. However, the molecular mechanism of BA against CRC cells was little reported. Here, we proved that BA elicited CRC cells' growth inhibition and apoptosis in a dose-dependent manner. In addition, BA treatment induced autophagy via inhibiting the AKT-MTOR signaling pathway. Inhibition of autophagy by either administration of autophagic inhibitor chloroquine or siRNA-mediated knockdown of ATG5 could augment BA-induced apoptotic cell death as well as inhibition of cell proliferation. Moreover, we found that p53 was firstly activated by short exposure to BA and then was rapidly degraded via the ubiquitin-mediated degradation pathway in both wtp53 and mutp53 CRC cells. Notably, more preferential cytotoxicity of BA was obtained in mutp53 cells (IC50 values: HT29, 125 μM; SW480, 58 μM) rather than wtp53 cells (IC50 values: HCT116, 178 μM). Further experiments demonstrated that siRNA-mediated p53 knockdown attenuated BA-induced autophagy, and forced overexpression of p53 augmented BA-induced autophagy, indicating that p53-enhanced BA-induced autophagy. Moreover, BA enhanced the sensitivity of mutp53 cells to chemotherapy drugs such as 5-FU and ADR by degradation of mutp53. Overall, our study proved that BA could induce CRC cell death by inducing apoptosis and reduce the overaccumulation of BA-induced protective autophagy by degrading wtp53 and mutp53 dependent on the ubiquitin-mediated degradation pathway to achieve killer effect, suggesting that BA might serve as a novel desirable drug for mutp53 cancer therapy.

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Helicteric Acid, Oleanic Acid, and Betulinic Acid, Three Triterpenes from Helicteres angustifolia L., Inhibit Proliferation and Induce Apoptosis in HT‐29 Colorectal Cancer Cells via Suppressing NF‐κB and STAT3 Signaling

Cited by 25 publications

References 44 publications

Overview of the STAT‑3 signaling pathway in cancer and the development of specific inhibitors (Review)

Overview of the STAT‑3 signaling pathway in cancer and the development of specific inhibitors (Review)

Fructus Ligustri Lucidi in Osteoporosis: A Review of its Pharmacology, Phytochemistry, Pharmacokinetics and Safety

Overaccumulation of p53-mediated autophagy protects against betulinic acid-induced apoptotic cell death in colorectal cancer cells

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