Combination of Platycodin D with docetaxel synergistically suppressed cell growth in DU-145 by enhancing apoptosis and alleviating autophagy

Jin, Yan; Li, Ying-Jiang; Ge, Dong-Sheng; Zhu, Lili; Wang, Yingyu; Luo, Jia; Shen, Bing-Yan; Jia, Qi-Qi; Cao, Chunyu; Wang, Wenbing; Feng, Na; Wu, Guoying; Yongquan, Chen

doi:10.1016/j.eujim.2021.101302

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…MCF-7 cells were seeded in a 96-well microplate overnight and incubated with compounds at different concentrations for 24 h. The 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay was used to calculate cell viability as described previously [ 22 ]. The results of the treated groups were normalized to the control group and then expressed as inhibition rates.…”

Section: Methodsmentioning

confidence: 99%

Identification of icaritin derivative IC2 as an SCD-1 inhibitor with anti-breast cancer properties through induction of cell apoptosis

et al. 2022

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Background Breast cancer is the most common malignancy affecting women, yet effective targets and related candidate compounds for breast cancer treatment are still lacking. The lipogenic enzyme, stearoyl-CoA desaturase-1 (SCD1), has been considered a potential target for breast cancer treatment. Icaritin (ICT), a prenylflavonoid derivative from the Traditional Chinese Medicine Epimedii Herba, has been reported to exert anticancer effects in various types of cancer. The purpose of the present study was to explore the effect of the new ICT derivative, IC2, targeting SCD1 on breast cancer cells and to explore the specific mechanism. Methods Immunohistochemistry and semiquantitative evaluation were performed to detect the expression level of SCD1 in normal and tumor samples. Computer-aided drug design (CADD) technology was used to target SCD1 by molecular docking simulation, and several new ICT derivatives were prepared by conventional chemical synthesis. Cell viability was evaluated by an MTT assay and dead cell staining. SCD1 expression in cancer cells was determined by Western blot and qRT-PCR analyses. The enzymatic activity of SCD1 was evaluated by detecting the conversion rate of [d31] palmitic acid (PA) using Gas chromatography-mass spectrometry (GC–MS). DAPI staining, flow cytometry and Western blot were used to detect cell apoptosis. Mitochondrial membrane potential and reactive oxygen species (ROS) assays were used to determine cell mitochondrial function. Lentiviral transduction was utilized to generate SCD1-overexpressing cell lines. Results We found that SCD1 was overexpressed and correlated with poor prognosis in breast cancer patients. Among a series of ICT derivatives, in vitro data showed that IC2 potentially inhibited the viability of breast cancer cells, and the mechanistic study revealed that IC2 treatment resulted in ROS activation and cellular apoptosis. We demonstrated that IC2 inhibited SCD1 activity and expression in breast cancer cells in a dose-dependent manner. Moreover, SCD1 overexpression alleviated IC2-induced cytotoxicity and apoptosis in breast cancer cells. Conclusions The new ICT derivative, IC2, was developed to induce breast cancer cell apoptosis by inhibiting SCD1, which provides a basis for the development of IC2 as a potential clinical compound for breast cancer treatment.

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Section: Methodsmentioning

confidence: 99%

Identification of icaritin derivative IC2 as an SCD-1 inhibitor with anti-breast cancer properties through induction of cell apoptosis

et al. 2022

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“…Platycodin D, a major bioactive compound derived from Platycodonis radix, has been widely used in traditional East Asian medicine to relieve respiratory discomfort. Recently, several studies have focused on the anticancer efficacy of platycodin D. Jin et al (2021) reported that platycodin D combined with docetaxel synergistically suppressed the growth of DU-145, prostate cancer cells. This action by the regulation of autophagy and apoptosis appears to be mainly due to EGFR-mediated pathways; reactive oxygen species (ROS), AMP-activated protein kinase, and P38 pathways are also presumed to have contributed.…”

Section: Resultsmentioning

confidence: 99%

Synergistic effects of natural products in combination with anticancer agents in prostate cancer: A scoping review

Cheon

2022

Front. Pharmacol.

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Background: Prostate cancer is the second most common cancer in men and has the fourth highest mortality among men worldwide. Different combination therapies for cancer are being tested, and among them, the integration of natural products is increasing. This study reviews research on the combination of anticancer drugs and natural products for the treatment of prostate cancer and suggests future directions in this field.Methods: Articles were identified by searching the PubMed, Embase, and Cochrane Library databases. Search keywords included the following: “Antineoplastic agents,” “Anticancer drug,” “Phytotherapy,” “Natural product,” “Drug synergism,” and “Synergistic effect”. The selection process focused on whether the differences in efficacy of anticancer drugs were evaluated when combined with natural products.Results: Nineteen studies were included. All 19 studies evaluated efficacy in vitro, as well as 10 in vivo. There were 13 studies on a single compound extracted from natural products, three studies on mushroom and herb extracts, and three studies on herbal medicines consisting of three herbs, and a dietary supplement containing 10 herbs. Cancer cell lines used were PC-3 in nine studies, LNCaP in six studies, C4-2 in five studies, DU-145 in four studies, and 22Rv1 in two studies. Anti-cancer drugs co-administered were as follows: docetaxel in nine studies, doxorubicin and enzalutamide in three studies, paclitaxel and suberoylanilide hydroxamic acid in two studies, and cisplatin, vincristine, and bicalutamide in one study each.Conclusion: Although prostate cancer is prevalent worldwide, there are relatively few studies on the use of natural products with anticancer agents as treatment. Since it has reported that the efficacy of anticancer drugs is enhanced by coadministration of natural products, it is necessary to conduct further studies on this.

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“…Additionally, in Jin's study, PLD could also accelerate apoptosis induced by other drugs like docetaxel. It was observed that cleaved PARP, caspase-3/9, and Bax/Bcl-2ratio were upregulated in the combination treatment group (Jin et al, 2021). Xu et al (2014b) studied on the effects of PLD on human glioma U251 cells.…”

Section: Prostate Cancermentioning

confidence: 99%

The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus

et al. 2023

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Chinese doctors widely prescribed Platycodon grandiflorus A. DC. (PG) to treat lung carbuncles in ancient China. Modern clinical experiences have demonstrated that PG plays a crucial role in treating chronic pharyngitis, plum pneumonia, pneumoconiosis, acute and chronic laryngitis, and so forth. Additionally, PG is a food with a long history in China, Japan, and Korea. Furthermore, Platycodin D (PLD), an oleanane-type triterpenoid saponin, is one of the active substances in PG. PLD has been revealed to have anti-inflammatory, anti-viral, anti-oxidation, anti-obesity, anticoagulant, spermicidal, anti-tumor etc., activities. And the mechanism of the effects draws lots of attention, with various signaling pathways involved in these processes. Additionally, research on PLD’s pharmacokinetics and extraction processes is under study. The bioavailability of PLD could be improved by being prescribed with Glycyrrhiza uralensis Fisch. or by creating a new dosage form. PLD has been recently considered to have the potential to be a solubilizer or an immunologic adjuvant. Meanwhile, PLD was discovered to have hemolytic activity correlated. PLD has broad application prospects and reveals practical pharmacological activities in pre-clinical research. The authors believe that these activities of PLD contribute to the efficacy of PG. What is apparent is that the clinical translation of PLD still has a long way to go. With the help of modern technology, the scope of clinical applications of PLD is probable to be expanded from traditional applications to new fields.

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Combination of Platycodin D with docetaxel synergistically suppressed cell growth in DU-145 by enhancing apoptosis and alleviating autophagy

Cited by 4 publications

References 33 publications

Identification of icaritin derivative IC2 as an SCD-1 inhibitor with anti-breast cancer properties through induction of cell apoptosis

Identification of icaritin derivative IC2 as an SCD-1 inhibitor with anti-breast cancer properties through induction of cell apoptosis

Synergistic effects of natural products in combination with anticancer agents in prostate cancer: A scoping review

The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus

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