# Capsaicin and small cell lung cancer therapy

> **NIH NIH R15** · MARSHALL UNIVERSITY · 2021 · $444,000

## Abstract

PROJECT SUMMARY
Capsaicin is the spicy, pungent ingredient of chili peppers. Conventionally, capsaicin is used as a pain-relieving
agent in over-the-counter analgesic creams and lotions. Our research data showed for the first time that
capsaicin triggered apoptosis in human small cell lung cancers (SCLCs). However, the development of
capsaicin as a feasible anti-cancer drug is limited by its low biological half-life, unpleasant side effects including
gut pain, hyperalgesia, stomach cramps and nausea. Biochemical studies have shown that capsaicin analogs
containing long chain unsaturated fatty acids in its C-terminal region (called N-AVAMs) were non-pungent and
possessed pain-relieving activity. Subsequently, we examined the anti-tumor activity of selected N-AVAM
capsaicinoids. We observed that the non-pungent N-AVAM capsaicin analog arvanil displayed greater pro-
apoptotic activity relative to capsaicin in human SCLCs. However, arvanil is a viscous liquid with poor solubility
properties. Based on the structural motifs of arvanil, the present R15 renewal application proposes structure-
activity relationship (SAR) studies to identify capsaicin analogs with improved bioavailability properties and anti-
tumor activity and in human SCLCs. Furthermore, arvanil sensitized platinum-resistant human SCLCs to
irinotecan-induced apoptosis. The chemosensitization activity of arvanil was greater than capsaicin in human
SCLCs. Using these observations as proof-of-concept, the current renewal application will test the
chemosensitization ability of a panel of non-pungent N-AVAM capsaicin analogs. The central hypothesis of our
renewal application is that the SAR studies will lead to the identification of capsaicinoids which, will
display robust anti-tumor activity as single agents and in combination with irinotecan in vivo. In addition,
we aim to investigate the bioavailability of these N-AVAM capsaicin compounds in mice models. An innovative
feature of our grant application is that we aim to test the anti-tumor activity and chemosensitization activity of
these capsaicin analogs in PDX models of human SCLCs. The experimental models outlined in our proposal
provide meaningful research experiences for undergraduate and graduate students. The results of our studies
will foster the hope of novel therapies in classical and platinum-resistant SCLCs.

## Key facts

- **NIH application ID:** 10045967
- **Project number:** 2R15CA161491-03
- **Recipient organization:** MARSHALL UNIVERSITY
- **Principal Investigator:** Piyali Dasgupta
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $444,000
- **Award type:** 2
- **Project period:** 2012-07-09 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045967

## Citation

> US National Institutes of Health, RePORTER application 10045967, Capsaicin and small cell lung cancer therapy (2R15CA161491-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10045967. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*