Overview & Objective
This is a unique database project of the Institute of East-West Medicine guided by an expert panel and under the direction of Dr. Raymond Chang , generously sponsored by the Gray Charitable Trust. The goal is to bring together materials from traditional Asian pharmacopoeias which have potential anti-cancer activity and to provide one unified source for such information with a special emphasis on translated results of laboratory, animal or human clinical experiments already published in native Asian journals or texts otherwise not easily accessible. The intent of all this is to encourage research and discovery which may hopefully lead to new cancer treatments.
Nature based treatments play
an essential role in the healthcare
of 80% of the world¡¯s population,
and there is an expanding need for
nature-based drug discovery to combat
a serious disease such as cancer.
Natural products with its vast molecular
diversity and biological functionality
remain a cornerstone of drug development
for cancer. In the plant kingdom alone,
there are greater than 250,000 species
of plants out of which more than one
thousand have been found to possess
significant anticancer properties(1)
. Between 1960-1981 for example, the
US National Cancer Institute screened
114,000 extracts from 35,000 plants
collected mainly in temperate regions
and hundreds of compounds have been
isolated from plant and marine source
to date based on cytotoxicity assays(2)
. Overall, it is estimated that between
0.4% to 1.8% of natural extracts (from
terrestrial plans to marine animals
respectively) of natural materia may
contain anti-cancer principles. From
1981-2002, there has been 30 new entities
for cancer that are natural products
or semi-synthetic modification of
natural products, based on approvals
by regulatory agencies such as the
US FDA(3) . Currently, over
50% of anticancer drugs approved by
the US FDA are nature-derived(4)
and over 60% of all drugs in clinical
trials for cancers are nature related
as of 2000(5). Such well-known
nature derived antineoplastic agents
in common oncology use include Vinblastine
and Vincristine (from Catharanthus
roseus), Etoposide (from Podophyllum),
Paclitaxel (from Taxus brevifolia)
and Topotecan (from Camptotheca acuminate).
Recently, Asian natural remedies have
also contributed significantly to
modern anti-cancer drugs notably Camptosar
(modified and derived from Chinese
ornamental tree Camptotheca acuminata)
and Arsenic trioxide (indirectly from
Composite Indigo naturalis(6)),
which have been successfully developed
into modern cancer drugs. Others such
as the CDK inhibitor Flavopiridol
(from Rohitukine(7), a chromone
alkaloid from Ochrosia leaves from
India), Gossypol (from cotton seed),
Artemisins (from Artemisia annua or
Wormwood) are currently in clinical
trials or pending further research
in the West. Then there are those
compounds that are in various stages
of preclinical and clinical development;
and many more nature derived materials
such as genistein, curcumin with Asian
dietary backgrounds have received
widespread attention as potential
chemopreventatives.
With the escalating knowledge of new
molecular targets for cancer and advancing
knowledge of other anticancer mechanisms
other than cytotoxicity such as immuno-modulation,
anti-angiogenesis and induction of
cell differentiation/apoptosis, many
more natural anti-cancer candidate
compounds can be identified in the
future. Also because of expanded prospecting
for natural anti-cancer compounds
from marine and other non-plant based
sources as well as new drug development
tools such as high-throughput screening
and advances in combinatorial chemistry
and genomics. Much original research
has already been done in Asia where
there is inherent familiarity with
the native pharmacopoeia but yet there
is no central resource for such material
and there is limited accessibility
by researchers on native studies,
which may have been carried out and
published, in Asian journals and in
native languages. This database project
intends to circumvent such limitations
by providing a central repository
of data and references related to
Asian materia medica and potential
cancer treatment, especially relating
to the translation of original research
either as abstract or in entirety
into English to facilitate communication,
reduce unnecessary replicative research
efforts, and promote further investigations
by the international scientific community.
This project currently has the most
comprehensive listing and upon completion
will be the largest and most complete
public database of Asian anti-cancer
materia (botanical or otherwise).
Methodology
& Search Strategy
In general,
the AAMD is guided by an evidence
based approach based on a Cochrane
review structure. We collaborate
with experts and academic centers
in Asia to attempt first to systematically
identify, and review existing paper
and electronic
bibliographies in English
and native languages in order to identify
all natural material medica which
has potential anti-cancer activity.
We then set to classify each material
by their nature, pharmacology, and
evidence of potential anti-cancer
activity. Each natural material will
be researched for synonymous or identical
materials by Scientific as well as
their native or folk names. The general
nature of the material will be described
along with the known pharmacology.
We will concentrate on known scientific
modes of anticancer activity. Evidence
of potential use against cancer will
be characterized as in vitro, animal
and clinical reports of biological
activity. Furthermore, reports of
safety of the materia for human use
will be represented by known toxicology
and side effects.
In the first phase of our project,
we will focus on Traditional Chinese
(includes Korean and Japanese) Materia
Medica. We systematically review and
cross reference bibliographies and
electronic databases by handsearch
or electronically in English and native
languages including nineteen reference
books and thirty-six online sites
for each material or herb. In Chinese
alone, we routinely search more than
20 databases with nearly a half million
citations (TCMLARS
alone, drawing from biomedical journals
published in China since 1984 has
400,100 records, whereas TCMD
has approximately 20,000 records from
up to 200 journals from Mainland China,
Taiwan and Hong Kong) and in PubMed
(National Library of Medicine, Bethesda,
MD) the database includes over fourteen
million citations dating back to 1957.
Extracts as well as abstract common
information (name, species, synonymous
names, occurrence, common use in traditional
medicine etc), known pharmacological
information (chemistry, activity,
pharmacodynamics, pharmacokinetics,
toxicity etc) and evidence of anti-cancer
efficacy (in vitro as well as vivo
and clinical trial data). The information
is then reviewed, edited and classified
with appropriate references and links
to original literature and subsequently
uploaded to our database using the
latest Quantum Art data management
system. Depending on funding, we intend
to produce a minimum of 30 monographs
a year on selected significant materials
from the database, each materia in
this format:
Nomenclature: includes Scientific
and Common Names (in English and Native
(transliterated) languages)
Botanical
Includes basic
information about description and
distribution of materia.
Pharmacology
Includes chemical
constituents, pharmacokinetics and
pharmacodynamics
Efficacy
Includes in
vitro, in vivo and clinical data and
ranked based on US National Cancer
Institute¡¯s guideline
for levels of evidence for
human studies of cancer and a 2003
interim guidance
for industry from the US FDA
for evidence-based ranking system
for scientific data.
Toxicity/Safety: includes adverse
reactions, known interactions, contraindications
and other precautions.
Results
(Ongoing: last update 10/20)
RESULTS Although the project¡¯s
intent is to eventually cover the
entire Asian region (includes China,
Japan, Korea, India, Mongolia, Tibet,
Thailand, Indonesia and the rest of
Southeast Asia), an initial survey
indicates that most 90% of the Asian
anti-cancer materia is found in the
Chinese and related pharmacopoeia.
The database begins
with a current listing of nearly 700
materia species of Sino (includes
Taiwanese, Japanese, Korean, Tibetan)
origin, and these in turn are (in
descending order) respectively of
terrestrial plant (80%), fungi (9%
),food
(3.5%), insect (3%), marine (1.8%), reptile (1.2), and mineral (1%)
origin.
It should be noted
that the scope and diversity of materia
with anticancer properties so far
identified by this database is astounding
especially when put into the perspective
that relatively few leads were generated
upon screening of tens of thousands
of materia by the National Cancer
Institute over a span of decades.
The classification difficulties encountered
in the initial identification of the
each material are that there may be
identical material under synonymous
scientific or common names or an outright
confusion of terminology used to identified
the same material. Each material frequently
containing multiple anti-cancer chemical
components while in turn each such
component may be present in various
unrelated species of materia further
compounds complexity. Additionally,
each anti-cancer component chemical
may have multiple modes of anti-cancer
activities and the synergism amongst
different components existing in the
same materia needs further to be taken
into account from an efficacy perspective.
In the case of native medical systems
such as Traditional Chinese Medicine
(TCM), cancer treatment is undertaken
within a unique theoretical framework
and may involve concepts of treatment
foreign to the Western oncologic approach
and thus defy current scientific understanding
of cancer biology. Examples of anti-cancer
TCM principles of cancer treatment
include: Fu Zheng Qu Xie, Huo Xue
Qu Yu, Qing Re Jie Du, Ruan Jian San
Jie, Yi Du Gong Du. The natural materia
employed using such TCM principles
may thus be difficult to screen using
conventional scientific assays e.g.
cytotoxicity assays, but may show
relevant benefit in a clinical setting.
Further complicating matters in TCM,
materia medica are usually not used
singly but as a cocktail or so-called
formula containing multiple constituents
with multiple therapeutic principles.
Thus while it would be a logical step
to eventually include research information
and incorporate such anti-cancer formulae
into our database at a future date,
this is not currently the mainstay
of AAMD.
1.
Mukherjee AK, et al. Advances in cancer
therapy with plant based natural products.
Curr. Med. Chem. 2001; 8:1467-86.
2. Cragg GM, et al. Ethnobotany and
drug discovery: the experience of
the US National Cancer Institute.
Ciba Found. Symp. 1994;185:178-90.
3. Newman DJ, Cragg GM, Snader KM.
Natural products as sources of new
drugs over the period 1981-2002. J.
Nat. Prod. 2003:66:1022-1037.
4.Kim J, Park EJ. Cytotoxic anticancer
candidates from natural resources.
Curr. Med. Chem. Anti-Canc. Agents.
2002;2:485-537.
5.Cragg GM, Newman DJ. Antineoplastic
agents from natural sources: achievements
and future directions. Expert Opin.
Investig. Drugs. 2000;9:2783-97.
6.Wang ZY. Arsenic compounds as anticancer
agents. Cancer Chemother. Pharmacol.
2001;48 Suppl 1: S72-6.
7.Arguello F, et al. Flavopiridol
induces apoptosis of normal lymphoid
cells, causes immunosuppression, and
has potent antitumor activity In vivo
against human leukemia and lymphoma
xenografts. Blood. 1998 ;91:2482-90.
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