Gigantol inhibits proliferation and enhances DDP-induced apoptosis in breast-cancer cells by downregulating the PI3K/Akt/mTOR signaling pathway

Huang, Jian; Liu, Chenxing; Duan, Shuna; Jiang, Lin; Luo, Yingyi; Tao, Shengchang; Xing, Shangping; Zhang, Xiaofeng; Du, Haiyan; Wang, Huan; Huang, Chunlei; Wei, Gang

doi:10.1016/j.lfs.2021.119354

Cited by 21 publications

(19 citation statements)

References 69 publications

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“…AKT's central role in the PI3Ks pathway makes it one of the most activated downstream effectors in the oncogenic landscape (Martini et al, 2014). Huang et al found that gigantol could inhibit the proliferation and significantly potentiate the anticancer activities of cisplatin (DDP) in breast cancer cells via the PI3K/Akt/mTOR signaling pathway (Huang et al, 2021). In our study, L. acidophilus KLDS1.0901 affected apoptosis through key genes of PTEN and AKT in the PI3K-Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 48%

Effects of Lactobacillus acidophilus KLDS1.0901 on Proliferation and Apoptosis of Colon Cancer Cells

et al. 2022

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Colon cancer is the most common type of malignant tumor. The cytotoxicity effect of lactic acid bacteria may be active by inhibiting cancer cell proliferation, producing anticancer compounds, and inducing apoptosis in cancer cells, but the mechanism is unclear. Our previous study revealed that Lactobacillus acidophilus KLDS1.0901 has good probiotic properties. In this study, We screened out the highest inhibition rate of L. acidophilus KLDS1.0901 and assessed the effects on the proliferation of HT-29, Caco-2, and IEC-6 cells. Then, the apoptosis mechanism of HT-29 cells was studied when treated with L. acidophilus KLDS1.0901. Results showed that L. acidophilus KLDS1.0901 inhibited the proliferation of HT-29 and Caco-2 cells in a dose-dependent manner and reached the maximum under the condition of multiplicity of infection (MOI) = 100 (rate of Lactobacillus to cells) at 48 h. With the increase in time and MOI, reactive oxygen species in HT-29 cells, the apoptosis rates of HT-29 cells were increased, and the amount of blue fluorescence of the cells was also increased after Hoechst 33258 staining. Furthermore, L. acidophilus KLDS1.0901 reduced the mitochondrial membrane potential of HT-29 cells. Notably, 1,133 differentially expressed genes were screened by transcriptomics research, including 531 up-regulated genes and 602 down-regulated genes. These genes were involved in the nuclear factor κB and PI3K-AKT signaling pathways related to the apoptosis of HT-29 cells. These findings suggested that L. acidophilus KLDS1.0901 has the potential to be used in the development of a new type of functional foods for adjuvant treatment of colon cancer.

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Section: Discussionmentioning

confidence: 48%

Effects of Lactobacillus acidophilus KLDS1.0901 on Proliferation and Apoptosis of Colon Cancer Cells

et al. 2022

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“…It is discovered that cisplatin (DDP) activates the NLRP3/caspase-1/GSDMD pathway to induce pyroptosis of BC cells to exert antitumor effects [ 186 ]. Furthermore, DDP induces apoptosis which is connected with downregulating the PI3K/Akt/mTOR signaling pathway in BC cells [ 187 ]. It is reported that pyroptosis of BC cells is induced with the AIM2/caspase-3/GSDME axis being activated when BC cells are administrated by dihydroartemisinin (DHA) [ 188 ].…”

Section: Pyroptosis and Cancermentioning

confidence: 99%

“…signaling pathway [169][170][171] 17β-estradiol Induces the activation of NLRP3 infammasome [173] Increases FOXO3 phosphorylation, induces oxidative stress, and downregulates IL-6/STAT3 signaling [174,175] Berberine Induces caspase-1-dependent pyroptosis [176] Regulates NF-κB/p65 pathway and induces adenosine AMPK-mediatedcaspase-dependent apoptosis [177,178] Euxanthone Promotes pyroptosis in a caspase-dependent manner [156] Alpinumisofavone Induces NLRP3 infammasome-mediated pyroptosis [157] Breast cancer Polydatin Downregulates the JAK2 and STAT3 levels [184] Suppresses the ROS/PI3K/Akt pathway [185] Cisplatin Activates the NLRP3/caspase-1/GSDMD pathway [186] Downregulates the PI3K/Akt/mTOR signaling pathway [187] Table 1: Continued.…”

Section: Hepatic Carcinoma Crizotinibmentioning

confidence: 99%

Targeted Pyroptosis Is a Potential Therapeutic Strategy for Cancer

Qian

Bai

et al. 2022

Journal of Oncology

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As a type of regulated cell death (RCD) mode, pyroptosis plays an important role in several kinds of cancers. Pyroptosis is induced by different stimuli, whose pathways are divided into the canonical pathway and the noncanonical pathway depending on the formation of the inflammasomes. The canonical pathway is triggered by the assembly of inflammasomes, and the activation of caspase-1 and then the cleavage of effector protein gasdermin D (GSDMD) are promoted. While in the noncanonical pathway, the caspase-4/5/11 (caspase 4/5 in humans and caspase 11 in mice) directly cleave GSDMD without the assembly of inflammasomes. Pyroptosis is involved in various cancers, such as lung cancer, gastric cancer, hepatic carcinoma, breast cancer, and colorectal carcinoma. Pyroptosis in gastric cancer, hepatic carcinoma, breast cancer, and colorectal carcinoma is related to the canonical pathway, while both the canonical and noncanonical pathway participate in lung cancer. Moreover, simvastatin, metformin, and curcumin have effect on these cancers and simultaneously promote the pyroptosis of cancer cells. Accordingly, pyroptosis may be an important therapeutic target for cancer.

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“…An analytical strategy combining UPLC-IT-TOF, network pharmacology, molecular docking and experimental verification as one of the most effective methods for exploring material basis and pharmacological mechanisms of complex natural drugs were established for explaining antitumor chemical constituents and mechanisms of D. nobile and D. officinale, the accurate-mass error of IT-TOF was slightly 29.06 ± 1.13 mmol L À1 and 13.53 ± 1.10 mmol L À1 respectively [22]. Gigantol was applied to reduce the viability of human breast cancer cells and destabilize tumors via inhibiting PI3K/AKT, PI3K/Akt/mTOR and JAK/STAT signaling pathways [20,23].…”

Section: Discussionmentioning

confidence: 99%

Rapid comparison of antitumor chemical constituents and mechanisms between Dendrobium nobile and Dendrobium officinale by UPLC-IT-TOF, network pharmacology and experimental verification

Liu

Zeng

et al. 2023

AChrom

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Dendrobium nobile and Dendrobium officinale as the main varieties of traditional Chinese medicine Dendrobium are widely used in clinic. The study aimed to systematically explore chemical constituents and their antitumor effect of D. nobile and D. officinale by ultra-performance liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UPLC-IT-TOF), network pharmacology and cancer cell experiments. D. nobile extract and D. officinale extract could significantly inhibit the proliferation of human lung cancer A549 cells, human liver cancer HepG2 cells and human breast cancer MCF-7 cells in the dose-dependent manner (P < 0.05), the antitumor effect of D. officinale extract was stronger than that of D. nobile extract at the same drug concentration. A total of 40 chemical constituents of D. nobile and D. officinale including phenanthrenes, bibenzyls and other types of compounds had been identified by UPLC-IT-TOF, LCMSsolution and MetID software according to retention times, accurate mass, MSn fragmentation, reference compounds and natural product databases. Phenanthrenes with good antitumor activity were mainly present in D. nobile, bibenzyls were the main compounds of D. officinale. Integrated networks of Herb-Compounds-Targets-Cancer revealed that gigantol, moscatilin, tristin, moscatin and densiflorol B were regarded as key antitumor compounds of D. nobile and D. officinale, D. nobile and D. officinale shared 7 targets accounting for 70% of the antitumor core targets, more than half of their antitumor KEGG pathways were similar. The results of molecular docking and western blotting experiments indicated that the antitumor mechanisms of D. nobile and D. officinale may be through inhibiting PI3K-Akt and HIF-1α signaling pathways.

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Gigantol inhibits proliferation and enhances DDP-induced apoptosis in breast-cancer cells by downregulating the PI3K/Akt/mTOR signaling pathway

Cited by 21 publications

References 69 publications

Effects of Lactobacillus acidophilus KLDS1.0901 on Proliferation and Apoptosis of Colon Cancer Cells

Effects of Lactobacillus acidophilus KLDS1.0901 on Proliferation and Apoptosis of Colon Cancer Cells

Targeted Pyroptosis Is a Potential Therapeutic Strategy for Cancer

Rapid comparison of antitumor chemical constituents and mechanisms between Dendrobium nobile and Dendrobium officinale by UPLC-IT-TOF, network pharmacology and experimental verification

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