Growth-Inhibitory and Anti-Invasive Activity of Natural Non-Pungent
Non-small cell lung cancer (NSCLC) comprises of a spectrum of lung cancers.
Out of these, lung adenocarcinoma (LAC) accounts for about 60% of all
NSCLC cases. One of the main challenges of LAC treatment is that by
the time the disease is detected the tumor has already invaded into
the surrounding tissue, lymph nodes and distant organs.
The long-term goal of our laboratory is to identify dietary
compounds, which can suppress the growth and metastasis of human LACs.
Specifically, our published data shows that capsaicin (the
spicy ingredient of chili peppers) suppresses the invasion of multiple
human lung cancers. However, the clinical application of capsaicin is
limited by its unpleasant side effects including gut pain,
hyperalgesia, stomach cramps and nausea.
This drawback could be circumvented by the identification of
capsaicin-like analogs, which retain the anti-tumor activity of
capsaicin but do not produce the “heat-sensation” of capsaicin.
Several convergent studies have identified natural
capsaicin-like compounds, namely capsiate and capsiconiate, which
display similar biological activity of capsaicin but do not possess
its pungent side effects. However, the anti-invasive activity of these
non-pungent capsaicin analogs is unknown.
Since the invasion of tumor cells is one of the crucial step of
metastasis, our data raise the possibility that these non-pungent
natural capsaicin-like compounds may attenuate tumor invasion in human
LAC. The main aim of this
research project is to compare the growth-inhibitory and anti-invasive
activity of capsiate, capsiconiate and capsaicin in human LAC cell
lines. Our hypothesis
will be explored in the following specific aim:
Aim 1: To compare the growth-inhibitory activity of capsaicin,
capsiate and capsiconiate in human LAC cell lines using MTT assays
Aim 2: To compare the anti-invasive activity of capsaicin, capsiate
and capsiconiate in in human LAC cell lines using spherical invasion
The studies in the present
grant may lead to the
development of novel non-pungent nutrition-based therapeutic agent for
the treatment of metastatic human LAC.