Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of Gastric cancer

Nivedita Arora, Osama Alsaied, Patricia Dauer, Kaustav Majumder, Shrey Modi, Bhuwan Giri, Vikas Dudeja, Sulagna Banerjee, Daniel Von Hoff, Ashok Saluja

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Article numbere0171827
JournalPLoS One
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2017

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irinotecan
stomach neoplasms
Tumor Burden
Stomach Neoplasms
Tumors
Down-Regulation
Cells
Nude Mice
neoplasms
cell lines
Prodrugs
Neoplasms
Cell Line
drugs
cell viability
Cell Survival
Stomach
Clinical Trials, Phase I
Gastrointestinal Neoplasms
Diterpenes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of Gastric cancer. / Arora, Nivedita; Alsaied, Osama; Dauer, Patricia; Majumder, Kaustav; Modi, Shrey; Giri, Bhuwan; Dudeja, Vikas; Banerjee, Sulagna; Von Hoff, Daniel; Saluja, Ashok.

In: PLoS One, Vol. 12, No. 2, e0171827, 01.02.2017.

Research output: Contribution to journalArticle

Arora, Nivedita ; Alsaied, Osama ; Dauer, Patricia ; Majumder, Kaustav ; Modi, Shrey ; Giri, Bhuwan ; Dudeja, Vikas ; Banerjee, Sulagna ; Von Hoff, Daniel ; Saluja, Ashok. / Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of Gastric cancer. In: PLoS One. 2017 ; Vol. 12, No. 2.
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AU - Giri, Bhuwan

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