TriptoSar (omtriptolide)

Interestingly, we found that a monomeric drug, Triptolide, is capable of alleviating the inhibitory effect of MTX on Notch signaling pathway. This study promotes our understanding of MTX-mediated regulation of Notch signaling and could provide ideas to alleviate MTX-induced myelosuppression.

Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, triptotriterpenic acid A and triptobenzene H might be the main hepatotoxic components of TwFH. Among them, only triptotriterpenic acid A presents direct hepatotoxicity. Triptobenzene H exerts indirect liver damage by activating macrophages. Parthenolide, triptolide, triptonide, celastrol, and demethylzeylasteral can directly and indirectly cause liver injury.

Upregulation of the cellular tumor antigen p53 (TP53) gene and downregulation of peroxisome proliferator-activated receptor gamma (PPARG) and signal transducer and activator of transcription 1-alpha/beta (STAT1) genes can prolong the survival time of patients with OS. Triptolide, kaempferol, and 5,8-Dihydroxy-7-(4-hydroxy-5 methyl-coumarin-3)-coumarin have a relatively high potential to become a treatment for patients with OS and improve 5-year survival of OS patients.

Notably, the present study showed that triptolide re‑sensitized DOX‑resistant leukemia cells to DOX. In conclusion, the present study indicated that Nrf2 served a critical role in leukemia cell resistance to DOX and triptolide‑induced ferroptosis and suggested a potential strategy of combination therapy using triptolide and DOX in leukemia treatment.

In conclusion, SPTLC2 may be associated with the antivascular and antitumor effects of TP, and SPTLC2 is expected to become a new marker for tumor therapy. HUVECs can promote the proliferation, migration, and invasion of HepG2 cells, which may be related to the S1P/sphingosine-1-phosphate receptor (S1PR) signaling pathway.

Subsequently, we showed that TPL reduced FLIP level in a transcription- and degradation-independent mechanism. Our findings suggest that TPL induces loss of FLIP at the post-transcriptional level independently of proteasome-mediated pathway, an additional mechanism of TPL sensitizing cancer cells to TNF-α-induced apoptosis.

Herein, a novel platform for anti-tumor drug delivery was developed by incorporating an amphiphilic stachydrine-octadecane conjugate (SS) as the mitochondria-targeting molecule onto the triptolide-liposome surfaces (SS-TP LPs)...In the Pan02 tumor-bearing mice, the SS-TP LPs showed significant efficacy in inhibiting tumor growth and reducing tumor size but synchronously exhibited specific mitochondria-targeting and much lower subacute toxicity compared with the free TP and TP LPs. Our study suggests that SS-TP LPs can be a promising anticancer drug delivery system for mitochondria-targeted therapy in pancreatic cancer.

The profound antitumor effects in the aggressive 786-0 RCC xenograft model are highly encouraging and warrant further preclinical studies and potential clinical trials of M this devastating disease. Correlative tumor studies to understand the mechanisms of M in vivo antitumor effects are underway and will be presented at the meeting.

Methods Herein, we identified two natural products triptolide (TPL) and hesperidin (HSP), dual targeting EGFR and PI3Kin BCa by network pharmacology and molecular modeling...Immunogenic cell death markers HMGB1 and CRT levels were evaluated both in vitro and in vivo after treatment so as to inhibit BCa proliferation and tumor growth. Conclusions Dual targeting nanoparticle may emerge as a novel paradigm in BCa treatment, providing a new approach for inducing immunogenic cell death in BCa care.

TP pretreatment increased apoptosis in TNF-α-stimulated gastric cancer cells, which are dependent on the disruption of the H19/miR-204-5p/NF-κB/FLIP axis. Cotreatment of TP and TNF-α is a better option for enhancing the anticancer effect and lowering the side effect of TP.

These dietary polyphenols include curcumin (CUR), resveratrol (RES), epigallocatechin gallate (EGCG), apigenin, triptolide (TPL), kaempferol, genistein and moscatilin...Dietary polyphenols are also used with radiotherapy and chemotherapy to improve antitumor immunity and shape a beneficial TIME. In conclusion, dietary polyphenols induce cancer cell pyroptosis and regulate the TIME, providing new ideas for safer cancer cures.

P1b, N=30, Recruiting, City of Hope Medical Center | Initiation date: Jul 2022 --> Mar 2022

No abstract available

Overall, our results indicated that TP attenuated LPS-induced activation of RAW 264.7 macrophages by inducing M1-to-M2 repolarization via repression of the mTOR/STAT3 signaling. Therefore, TP might be an effective agent for IBD treatment.

Triptolide also sensitised cells to gemcitabine and induced apoptosis in a 3D model of NSCLC. Brusatol has off-target effects; however, triptolide may have potential use as a targeted adjuvant therapy in NSCLC.

Moreover, by upregulating HSP70 transcription, triptolide contributed to the protein degradation of the GOF mutp53. Our study reports, for the first time, the mechanism underlying triptolide-regulated protein degradation of TP53 or TP53, which offers new insight into developing a better therapeutic strategy for patients with NSCLC who express the unfolded mutp53 GOF protein.

P1b, N=30, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting

Further analysis indicated that TPL induced the demethylation of these genes, which may be related to the inhibited expression of methyltransferases DNMT1 and DNMT3a. In conclusion, our results suggest that TPL inhibits T-ALL by inhibiting aberrant epigenetic events in dysregulated Wnt signalling.

The management of unfit and older patients with acute myeloid leukemia should be personalized and be the result of evaluating patient- and disease-specific factors that are essential to their care. Combinations that include venetoclax are an increasingly well-documented option for many of them.

No abstract available

Triptolide (TP), a potent cytotoxin was then set as the model payload for dextran conjugation...Furthermore, the conjugate attained a more favorable therapeutic outcome in the tumor immune microenvironment than the free drug, preserving the fraction of T cells and their effector cytokines. In summary, macropinocytic dextran was able to provide drug delivery selectivity towards KRAS mutant cancer cells and reduce tumor immunity depletion caused by the cytotoxic drug in pancreatic cancer.

Our results revealed that Triptolide monotherapy exerted its antileukemia effect via both p53-dependent and independent ways, with the latter through perturbation of the MYC-ATF4 axis-mediated ER stress. Collectively, these data suggested that the Triptolide-Nutlin-3a combination might be a novel potential therapeutic intervention for patients with AML and it warrants further clinical evaluations.

Overall, our findings may provide a translational strategy to overcome cisplatin-resistant OC and offer a potential solution for the treatment of other cisplatin-resistant tumors.

Our results have shown for the first time the potent in vitro and in vivo antitumor effects of T in RCC and the molecular changes associated with these effects. The profound antitumor effects in the aggressive 786-0 RCC xenograft model are highly encouraging and warrant further preclinical studies and potential clinical trials of M this devastating disease. Correlative tumor studies to understand the mechanisms of M in vivo antitumor effects are underway and will be presented at the meeting.

TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC.

P1b, N=30, Not yet recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Initiation date: Dec 2021 --> Jul 2022 | Trial primary completion date: Dec 2023 --> Dec 2024

The expression level of Bcl-2 protein was (0.21±0.02), lower than (0.52±0.05) in 4 Gy group (P<0.05). Triptolide increases the radiosensitivity of radiation-induced lung cancer cells by inhibiting DNA repair and inducing apoptosis.

P1b, N=30, Not yet recruiting, City of Hope Medical Center

In conclusion, the new finding of the manuscript is that METTL3 enhances the mRNA stability of SLC7A11 via mA-mediated binding of IGF2BP2, which thus promotes OSCC progression, and triptolide inhibits OSCC by suppressing METTL3-SLC7A11 axis. Triptolide has a potential to be as an effective anti-OSCC drug targeted to METTL3.

The levels of CEA and CA19-9 in the two groups after treatment were lower than those before treatment, and the levels of CEA and CA19-9 in the combined group were lower than those in the control group (P & Lt; 0.05). The first-line treatment of recurrent nasopharyngeal Carcinoma with triprimmab combined with chemotherapy has a good clinical effect and has a broad clinical research prospect.

We considered that triptolide could treat thyroid cancer by inhibiting cell proliferation, inducing apoptosis and inhibiting inflammatory pathways such as the NF-κB and MAPK signaling pathways. CDKN1A, c-JUN, RELA, and TP53 were involved in the antithyroid cancer mechanism of triptolide.

More importantly, TPL@MP-LP treatment suppressed tumor growth but showed minimal damage to liver and renal functions. TPL exerted anticancer effects on HCC via inducing cell proliferation arrest, apoptosis, and necroptosis, and the MP-LP might be a promising delivery strategy to improve the antitumor efficacy while mitigating toxicity of TPL for HCC therapy.

TP can inhibit glioma cell proliferation, migration, and invasion, and reverse EMT progression. The possible mechanism of EMT reversal in glioma cells is that TP induces autophagy.

Furthermore, TP/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling pathway. Overall, TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity.

Many studies have confirmed that triptolide (TPL), one of the principal components of Tripterygium wilfordii, possesses broad-spectrum anti-tumor activity...Animal experiments showed that TPL, particularly TPL + cisplatin (DDP), significantly reduced the tumor burden, prolonged the life span of mice by inhibiting M2 macrophage polarization, and downregulated the levels of CD31 and CD206 (CD31 is the vascular marker and CD206 is the macrophage marker), the mechanism of which may be related to the inhibition of the PI3K/Akt/NF-κB signaling pathway...Our results highlight the importance of M2 TAMs in Epithelial Ovarian Cancer (EOC) migration ability, invasiveness, and resistance to DDP. We also preliminarily explored the mechanism governing the reversal of the polarization of M2 macrophages by TPL.

Molecular docking demonstrated a high affinity between triptolide and CXCR4. In conclusion, CXCR4 may be a therapeutic target of triptolide in the treatment of STAD patients by modulating the TME.

Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity.

This study not only provides a new paradigm of TPL in cancer therapy, but also highlights a crucial role of mitochondrial HK-II in linking glucose metabolism with pyroptosis.

In addition, a Transwell assay revealed that triptolide reduced the ability of MCF-7 cells to invade Matrigel. These data demonstrate that the anti-invasive effect of triptolide is associated with the inhibition of ERK signaling and NF-κB and AP-1 activation, and suggest that triptolide may be a promising drug for breast cancer.

In the present study, we determined the efficacy of Minnelide, a prodrug which is converted to its active form (Triptolide) in vivo against cervical cancer cells. Furthermore, Minnelide treatment was more effective when combined with platinum-based chemotherapy. These studies show that Minnelide can be used to inhibit the growth of cervical cancer.

However, when NICD 1 was ectopically overexpressed in the cells, it partially rescued proliferation and mammosphere formation of the cells, supporting the role of notch signaling. Together, these data demonstrate that targeting stem cells and the notch signaling pathway may be an effective strategy for curtailing TNBC progression.

These results demonstrate that triptolide suppresses NSCLC metastasis by targeting EMT via reducing β-catenin expression. Our study implies that triptolide may be developed as a potential agent for the therapy of NSCLC metastasis.