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Ref Type Journal Article
PMID (28192510)
Authors Arora N, Alsaied O, Dauer P, Majumder K, Modi S, Giri B, Dudeja V, Banerjee S, Von Hoff D, Saluja A
Title Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of gastric cancer.
Journal PloS one
Vol 12
Issue 2
Date 2017
URL
Abstract Text Gastric cancer is the third leading cause of cancer related mortality worldwide with poor survival rates. Even though a number of chemotherapeutic compounds have been used against this disease, stomach cancer has not been particularly sensitive to these drugs. In this study we have evaluated the effect of triptolide, a naturally derived diterpene triepoxide and its water soluble pro-drug Minnelide on several gastric adenocarcinoma cell lines both as monotherapy and in combination with CPT-11.Gastric cancer cell lines MKN28 and MKN45 were treated with varying doses of triptolide in vitro. Cell viability was measured using MTT based assay kit. Apoptotic cell death was assayed by measuring caspase activity. Effect of the triptolide pro-drug, Minnelide, was evaluated by implanting the gastric cancer cells subcutaneously in athymic nude mice.Gastric cancer cell lines MKN28 and MKN45 cells exhibited decreased cell viability and increased apoptosis when treated with varying doses of triptolide in vitro. When implanted in athymic nude mice, treatment with Minnelide reduced tumor burden in both MKN28 derived tumors as well as MKN45 derived tumors. Additionally, we also evaluated Minnelide as a single agent and in combination with CPT-11 in the NCI-N87 human gastric tumor xenograft model.Our results indicated that the combination of Minnelide with CPT-11 resulted in significantly smaller tumors compared to control. These studies are extremely encouraging as Minnelide is currently undergoing phase 1 clinical trials for gastrointestinal cancers.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Minnelide Minnelide is a water-soluble prodrug of the naturally derived diterpene triepoxide, triptolide, which induces apoptosis and inhibits cell proliferation, leading to reduced tumor growth (PMID: 28192510).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown gastric adenocarcinoma not applicable Irinotecan + Minnelide Preclinical - Cell line xenograft Actionable In a preclinical study, Minnelide and Camptosar (irinotecan) combination treatment resulted in increased inhibition of tumor growth in a cell line xenograft model of gastric adenocarcinoma compared to either Minnelide or Camptosar (irinotecan) treatment alone (PMID: 28192510). 28192510
Unknown unknown gastric adenocarcinoma not applicable Triptolide Preclinical - Cell culture Actionable In a preclinical study, treatment with Triptolide (C1572) induced apoptotic cell death and resulted in decreased cell viability in gastric adenocarcinoma cell lines in culture (PMID: 28192510). 28192510
Unknown unknown gastric adenocarcinoma not applicable Minnelide Preclinical - Cell line xenograft Actionable In a preclinical study, Minnelide treatment inhibited tumor growth and induced regression in gastric adenocarcinoma cell line xenograft models (PMID: 28192510). 28192510