# Anti-cancer effects of tocotrienols and a carboxychromanol in an innovative colon cancer model

> **NIH NIH R03** · PURDUE UNIVERSITY · 2024 · $74,517

## Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer death, but there is no effective treatment for the
late-stage cancer. Early detection with colonoscopy appeared to lower CRC risk but not associated death. To
reduce cancer mortality, it is important to develop effective agents for inhibiting high-risk CRC in people with
cancer driver mutations and adenomas. Although inhibition of cyclooxygenases (COX-1/-2) by NSAIDs including
aspirin have been recognized for preventing CRC, long-term use of NSAIDs is limited due to side effects and
moderate anticancer efficacy. It is therefore necessary to search for alternative and improved preventive
strategies and agents. Research has shown that pro-inflammatory 5-lipoxygenase (5-LOX) promotes colon
cancer development and may be a target for inhibiting CRC. Further, nuclear factor (NF)-κB and JAK-STAT3
are known to contribute to inflammation and promotion of CRC. Importantly, we and others have shown that γ-
and δ-tocotrienol (γTE, δTE), which are members in the vitamin E family, inhibit 5-LOX activity, NF-κB and STAT3
activation and the growth of cancer cells. δTE-13’-COOH, a metabolite of δTE, has been shown to be a unique
inhibitor of COXs and 5-LOX. In agreement with these findings, a δTE/γTE (8/1) mixture and δTE-13’-COOH
have been reported to inhibit chemically-induced colon cancer in mice. Based on these observations, we
hypothesize that δTE/γTE and δTE-13’-COOH are novel and effective preventive agents against CRC. Despite
existing evidence supporting our hypothesis, there are key knowledge gaps hindering translation of the use of
these promising agents to the clinic. In particular, the anticancer effects of these compounds have not been
examined in a “human-like” CRC model. The objective of this application is to delineate the anticancer effects
and mechanisms of δTE/γTE and δTE-13’-COOH in an innovative CRC model (AKC), which like CRC patients,
has mutant Apc and Kras and spontaneously develop adenoma tumors in the large intestine. Significance: The
success of this study will develop new cancer-preventive agents, generate preliminary data for R01 application
to further validate these compounds for CRC prevention, and offer key preclinical data for translation of basic
research to the clinic.

## Key facts

- **NIH application ID:** 10872735
- **Project number:** 1R03CA283236-01A1
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Qing Jiang
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,517
- **Award type:** 1
- **Project period:** 2024-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872735

## Citation

> US National Institutes of Health, RePORTER application 10872735, Anti-cancer effects of tocotrienols and a carboxychromanol in an innovative colon cancer model (1R03CA283236-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10872735. Licensed CC0.

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