| Pawpaw Root
kills Prostrate Cancer |
Date Written |
2007 |
| Author |
Joe Holmes |
Date Revised |
Nov. 24 09 |
This page has a collection
of 23 research reports showing Pawpaw root kills prostate cancer
hundreds, thousands, and even up to 100 million times the leading
chemo drug of adriamycin
see report #7 by Perdue University below
The facts on this page are indicative of the power of natural
compounds vs the dangerous side effects of altered drugs. The medical
industry is ignoring these scientifically proven medical facts proven
by doctors and not telling us about them. There is only one reason
our doctors are not telling us about them and that is the compelling
power of the drug companies through the FDA to protect their profits
at the expense of our lives. Did you know their power is excerted
by our government through the FDA who will not allow doctors to
prescribe herbs even when they are proven to be better and safer.
If you or I had a life saving product that would save the life of
dying people and failed to tell them about it would not the courts
hold us liable? For example have not the courts many times held
persons and companies liable for creating a product that was unsafe?
Annonaceous acetogenins are powerful anticancer
chemicals found in the Annonaceae family of trees (usually
called Pawpaw, Soursop, Custard-apple or Graviola trees). These chemicals are in high concentrations throughout the tree including
the fruit (over 2% of the dry weight of the fruit is Annonaceous
acetogenins see research # 3 below). The fruit is very tangy
and delicious and eaten daily (anticancer chemicals and all)
by many people in some parts of the world (it is the South
American equivalent of Lemonade in the US). Annonaceous acetogenins
are nontoxic (and tasty) and used medically in South America.
For anyone that is wondering, yes this is the same Pawpaw
that Baloo the bear in Walt ‘Disney’s animated
movie “The Jungle book” sings about
in the song “The Bare Necessities”...Doxorubicin and
Adriamycin are toxic Anthracycline type drugs and are among
the most effective cancer killing chemotherapy drugs used
by Drs. Unfortunately they
are also among the most toxic and are very destructive to
your heart. If the Drs. are trying to use them on you,
kiss your heart goodbye. (see research #1 & 2)...Anthracyclines
are among the most powerful, effective and toxic chemotherapy
drugs used on “Multiple Drug Resistant” (MDR) cancer (see
research # 1 & 2) so Annonaceous
acetogenins are commonly tested against Anthracyclines
(see # 6--22 below). Most people find it hard to believe that
Pawpaw can be so many times more effective than a FDA approved
Chemo super drug, so medical research is provided to prove
it. To get a feel of how much more powerful Pawpaw
chemicals are than chemotherapy drugs, look at research summary
#7, #17, #19 and #22.. potency
of over 100
million times that of Adriamycin (Notice this
is even a very respected American medical research center
saying this)
Will Annonaceous acetogenins
kill all cancer?
NO, Annonaceous acetogenins
work by various methods to block cancer cells from getting the ATP
(energy) produced by Mitochondria that is needed by cancer for fast
growth and or defense from chemotherapy and radiation (see # 4 &
5). Annonaceous acetogenins have little effect on slow growing and
easy to kill cancer because the amount of ATP needed by these cancers
is only a little more than needed by healthy cells. Also some energy
dependant cancers can make enough energy without using the Mitochondria
to survive. However many fast growing or Multiple Drug Resistant
(MDR) cancers have high ATP needs and are dependant on Mitochondria.
These cancers are hit extremely hard by Annonaceous acetogenins
without affecting normal cells (see # 21). The effect of Annonaceous
acetogenins on Mitochondria dependant cancer that is both fast growing
and MDR is absolutely amazing!
Caution;
Driving a
car or operating machinery while on very high doses is as dangerous
as taking Valium.
Toxicity;
This is a part of the diet of millions
of people and it took some digging to find any problems. However
high consumption of Annonaceous acetogenins for several decades
can interfere with brain ATP needs in some people and cause a type
of Parkinson’s disease (see# 23). This is very rare even with heavy
long-term usage so several months usage to kill cancer is very safe.
Are Annonaceous acetogenins
available?
Yes but no single Annonaceae
tree has all types so it takes a combination. Annona muricata (sometimes
called Amazon Pawpaw or Graviola) and Asimina triloba (commonly
called American Pawpaw) are readily available and between them should
contain all of the Annonaceous acetogenins tested in # 6—22 below."
Below are 23 scientific research
reports about Pawpaw and Gaviola Fruit. In order to be as brief
as possible only portions of each report are quoted. However anyone
who wants to read the actual research report can click the link.
1.
Doxorubicin
is one of the most effective chemotherapeutic agents used in the
treatment of malignancies.
Cardiotoxicity is the most important dose-limiting
toxicity of doxorubicin. Although cardiomyopathy is the most well known side effect
of doxorubicin, it usually occurs many years after the treatment
and relates to cumulative
doxorubicin dosage. Another form of doxorubicin cardiotoxicity
is arrhythmia which may occur at any time and after any dosage.
.
copy 15878560 then click PMID
and paste the number in their search box
2:
This report shows
the dangers of chemo drugs "...Anthracycline-induced
cardiotoxicity in children with cancer ...The
fact that anthracyclines are cardiotoxic seriously narrows their
therapeutic index in cancer therapy. The cardiotoxic
risk increases with the cumulative dose and may lead
to congestive heart failure (CHF) and dilated cardiomyopathy in
adults and in children. The prevention of anthracycline-induced cardiotoxicity is
particularly important in children who can be expected to survive
for decades after being cured of their malignancy...In
the presence of CHF, recovery with digitalis-diuretic
therapy alone seldom occurs, and in patients who have
refractory hemodynamic decompensation, heart transplantation is
indicated. copy 15871628 then click PMID
and paste the number in their search box
3:
Various plant parts of the paw paw tree
(Asimina triloba Dunal, Annonaceae) were extracted
and partitioned to concentrate the mixture of acetogenins into a
standardized pesticidal extract (F005).
A bioassay with brine shrimp larvae (Artemia
salina Leach) was used to determine the relative potencies of the
various extracts. The small twigs (0-0.5
cm diameter) yielded the most potent extract
(LC50 = 0.04 ppm); the stem wood (LC50 = 4.9 ppm) and leaves (LC50
= 53.7 ppm) yielded the
poorest activities. The unripe fruits, seeds, root wood,
root bark, and stem bark were notably
potent and, generally, yielded > 2% of their
dry weight as F005. The smaller diameter stems were more potent
than the larger stems.
copy
1464691 then click PMID
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4:
The Annonaceous
acetogenins are promising new antitumor and pesticidal agents
that are found only in the plant family
Annonaceae. Chemically, they are derivatives of
long-chain fatty acids. Biologically, they exhibit their potent
bioactivities through depletion
of ATP levels via inhibiting complex I of mitochondria
and inhibiting the NADH oxidase of plasma membranes of tumor cells.
Thus, they thwart ATP-driven
resistance mechanisms. copy 10096871
then click PMID
and paste the number in their search box
5: "ATP
depletion is the mode of action of the Annonaceous acetogenins,
and these agents
offer a special advantage in the chemotherapeutic treatment of MDR
tumors that have ATP-dependent
mechanisms. copy 9097981 then
click PMID
and paste the number in their search box
6:
Bioactivity-directed
fractionation of the seeds of Asimina triloba resulted in the
isolation of asimitrin (1) and 4-hydroxytrilobin (2). Compounds 1 and 2 showed
cytotoxic selectivity, with 100-10,000 times the potency of adriamycin
against prostate adenocarcinoma
(PC-3) and colon adenocarcinoma (HT-29) cell lines. copy 15730242 then
click PMID
and paste the number in their search box
7:
"The
bark extracts of Annona squamosa yielded a new bioactive acetogenin,
squamotacin (1),
and the known compound, molvizarin (2), which is new to this
species. Compound 1 is identical to the
potent acetogenin, bullatacin (3), except that
the adjacent bistetrahydrofuran (THF) rings and their flanking hydroxyls
are shifted two carbons
toward the gamma-lactone ring. Compound 1 showed cytotoxic selectively
for the human prostate tumor cell line (PC-3), with a potency
of over 100 million
times that of Adriamycin.
" copy 8991957 then click PMID
and paste the number in their search box
8: "Systematic
synthesis of mono- and bis-THF ring cores, synthetic intermediates
of antitumor
annonaceous acetogenins, has been achieved by asymmetric alkynylation and
subsequent stereodivergent THF ring formatio Systematic
synthesis of mono- and bis-THF ring cores, synthetic intermediates
of antitumor annonaceous
acetogenins, has been achieved by asymmetric alkynylation and
subsequent stereodivergent THF ring formation as key steps. The
asymmetric alkynylation of alpha-oxyaldehyde
and alpha-tetrahydrofuranic aldehyde with (S)-3-butyne-1,2-diol
derivatives gave good yield with very high diastereoselectivity.
These adducts were converted into mono- and bis-THF cores via
two kinds of one-pot THF ring formation, respectively. In addition,
the total synthesis of murisolin,
which shows cytotoxic activity against human tumor cell
lines with potency from 10(5) to 10(6) times that of adriamycin, was also achieved." copy
15467275 then click PMID
and paste the number in their search box
9:
" Annonaceous
acetogenins have potent antitumor effect in vitro and in vivo.
Squamocin is one of the annonaceous
acetogenins and has been reported to have antiproliferative
effect on cancer cells. Our results from
this study showed that squamocin
inhibited proliferation of HL-60 cells with IC50 value of 0.17
microg/ml and induced apoptosis of
HL-60 cells. Investigation of the mechanism of
squamocin-induced apoptosis revealed that treatment of HL-60
cells with squamocin
resulted in extensive nuclear condensation. DNA fragmentation,
cleavage of the death substrate
poly (ADP-ribose) polymerase (PARP) and induction
of caspase-3 activity. Pretreatment
of HL-60 cells with caspase-3 specific
inhibitor DEVD-CHO prevented squamocin-induced DNA fragmentation,
PARP cleavage and cell death. The
expression levels of protein bcl-2, bax have no change
in response to squamocin treatment in HL-60 cells, whereas
stress-activated protein kinase (SAPK/JNK)
was activated after treatment with squamocin
in HL-60 cells. These results suggest that apoptosis of HL-60 cells
induced by squamocin requires caspase-3 activation
and is related to SAPK activation".
copy 11883704 then click
PMID
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10:
" A
novel and two known bioactive mono-tetrahydrofuran (THF) annonaceous
acetogenins, annomocherin (1),
annonacin (2) and annomontacin (3), have been isolated
from the fractionated ethanolic extracts of the seeds of Annona
cherimolia, guided by the brine shrimp lethality
test (BST). Their structures were
elucidated on the basis of spectroscopic and chemical methods. All
compounds have a relative stereochemistry
of threo/trans/threo for the mono-THF ring
with two flanking hydroxyls. Compound 1 has a double bond at C-23/24
of aliphatic chain. Compound 1
was isolated from natural sources for the first time,
and was named annomocherin. Two known Compounds 2 and 3 which have
never been isolated from this species
before, were obtained. Compound 1 exhibited potent
and selective cytotoxicities against the breast carcinoma (MCF-7)
and kidney carcinoma
(A-498) cell lines with 100 to 1,000 times the potency of
adriamycin. In
brine shrimp lethality test (BST), 1-3 exhibited cytotoxicity."
copy 11534761 then click
PMID
and paste the number in their search box
11:
" Two
new cytotoxic annonaceous acetogenins, named uvarigrin(1) and uvarigrandin
A(3), were obtained from the roots of Uvaria grandiflora Roxb(Annonaceae). Based on X-ray analysis and Mosher's methodology, the overall
absolute configuration of 1 was established as 15S, 17R,
18R, 21R, 22R, 36S. The absolute configuration of 3 was
also resolved by Mosher's methodology. The relative configuration
of the previously reported uvarigranin (2) was revised.
Compound 1 showed cytotoxicity
against HCT-8, Bel7402 and A2780 human tumor cell lines at ED50
levels of 0.15, 0.21 and 0.41 microgram.ml-1, respectively. "
copy 11499032 then click
PMID
and paste the number in their search box
12:
" Two
new cytotoxic annonaceous acetogenins, annomolin (1) and annocherimolin
(2), were isolated from an
ethanolic extract of the seeds of Annona cherimolia. Annomolin
has a mono-THF ring with one flanking hydroxyl and possesses a
1,2-diol at C-7/8 of the aliphatic
chain. Annocherimolin has a mono-THF ring with
two flanking hydroxyls and possesses a double bond at C-21/22. Their
structures were elucidated by spectral data
and chemical derivatization. Compound
1 showed cytotoxic selectivity for the human prostate tumor cell
line (PC-3), with
a potency of over 10,000 times that of adriamycin. Compound 2
showed cytotoxic potencies
about 10,000 times those of adriamycin in the breast
(MCF-7) and colon (HT-29) cancer
cell lines." copy
11325235 then click PMID
and paste the number in their search box
13:
" Asitrocin
(1) and the mixture of (2,4)-cis- and trans-asitrocinones (2 and
3), new bioactive Annonaceous
acetogenins, were isolated from the seeds of Asimina
triloba by activity-directed fractionation using the brine shrimp lethality
test. Asitrocin and the mixture of (2,4)-cis-
and trans-asitrocinones have a configuration
of erythro/trans/threo from C-15 to C-20, the mono-THF moiety with
two flanking hydroxyl groups. The structures
were determined by spectroscopic methods.
These acetogenins showed potent bioactivities in the brine shrimp
lethality test (BST) and among six human
solid tumor cell lines with notable selectivity
for the prostate (PC-3) and the pancreatic (MIA PaCa-2) cell lines
at 10-100 times the potency
of adriamycin. " copy 11087592
then click PMID
and paste the number in their search box
14:
" cis-Annonacin
(1) and the mixture of (2,4)-cis-and trans-isoannonacins (2 and
3), three known mono-tetrahydrofuran
annonaceous acetogenins, have been isolated from the seeds
of Annona cherimolia by the use of the brine shrimp lethality
test (BST) for bioactivity directed fractionation.
Their structures were elucidated
based on spectroscopic and chemical methods. 1 showed potent
cytotoxicities in the brine shrimp
lethality test (BST) and among six human solid
tumor cell lines with notable selectivity for the pancreatic cell
line (PaCa-2) at
about 1,000 times the potency of adriamycin. The mixture of 2 and
3 is over 10,000
times cytotoxic as adriamycin in the pancreatic cell line
(PaCa-2). All of the compounds
are about 10 to 100 times as cytotoxic as adriamycin
in the prostate cell line (PC-3). " copy 10549583
then click PMID
and paste the number in their search box
15:
" Two
new bioactive Annonaceous acetogenins, annoglaxin (1) and
27-hydroxybullatacin (2),
have been isolated from the fractionated ethanolic extracts
of the leaves of Annona glabra, directing the fractionation with
the brine shrimp lethality test
(BST). The structures of 1 and 2 were elucidated on the
basis of spectroscopic and chemical methods, and the absolute
stereochemistries were determined by the advanced
Mosher ester method. 1 presents
unusual features of an OH at C-8 and a carbonyl at C-12 and, while
less potent than 2, shows interesting
selectivity for the human breast carcinoma (MCF-7)
cell line. Compound 2 was at least 100 000 times more potent
than adriamycin against
the human kidney carcinoma (A-498), prostate carcinoma
(PC-3), and pancreatic carcinoma
(PACA-2) cell lines in our panel of six human solid
tumor cell lines."
copy 10395501
then click PMID
and paste the number in their search box
16:
"The
seeds of Asimina triloba have yielded two novel cytotoxic
mono-tetrahydrofuran (THF) Annonaceous
acetogenins, asitrilobins A (1) and B (2). In addition, annonacin, asimin
and asiminacin, which are known, and annomontacin
and xylomaticin, which are known but are new in this species, were
obtained. Compounds 1 and 2 have a relative
stereochemical relationship of erythro/cis/threo
across the mono-THF ring with its two flanking hydroxyls and
they, thus, represent a new type of acetogenin.
Their structures were established
on the basis of chemical and spectral evidence. 1 and 2 showed
potent bioactivities in the brine shrimp lethality
test (BST) and among six human
solid tumor cell lines with notable selectivity for the pancreatic
cell line (MIA PaCa-2)
at ten to one-hundred times the potency of adriamycin. " copy 10385998
then click PMID
and paste the number in their search box
17:
"Continuing work on the bioactivity-directed
fractionation of the bark of Annona squamosa
has resulted in the discovery of three new Annonaceous acetogenins,
(2,4-cis and trans)-squamolinone (1), (2,4-cis
and trans)-9-oxoasimicinone (2), and
bullacin B (3). Compounds 1-3 are all adjacent bis-THF
ring acetogenins with 2 representing
the first bis-ring acetogenin to contain a carbonyl along its
aliphatic chain. Compound 3 was selectively
cytotoxic in a panel of six human tumor
cell lines with a potency of nearly a million times that of adriamycin
against the MCF-7 (human breast
adenocarcinoma) cell line."
copy 9629470 then
click PMID
and paste the number in their search box
18: "Fourteen
structurally diverse Annonaceous acetogenins, representing the three
main classes of bis-adjacent, bis-nonadjacent,
and single-THF ring(s), were tested for their ability
to inhibit the growth of adriamycin resistant human mammary
adenocarcinoma (MCF-7/Adr) cells. This cell line is resistant to
treatment with adriamycin, vincristine,
and vinblastine and is, thus, multidrug resistant
(MDR). Among a series of bis-adjacent
THF ring acetogenins, those with the
stereochemistry of threo-trans-threo-trans-erythro (from C-15
to C-24) were the most potent
with as much as 250 times the potency of adriamycin. A spacing of 13 carbons between the
flanking hydroxyl of the THF ring system and the gamma-unsaturated
lactone seems to be optimum with a spacing of 11 and 9 carbons
being significantly less active. Several single-THF
ring compounds were also quite
potent with gigantetrocin A (11) being the most potent compound
tested. The
acetogenins may, thus, have chemotherapeutic potential, especially
with regard to MDR
tumors." copy
9207950 then click PMID
and paste the number in their search box
19:
"Trilobalicin
(1), a new nonadjacent bis-THF ring annonaceous acetogenin,
2,4-cis- (2) and 2,4-trans-trilobacinone
(3), the ketolactones of trilobacin, an adjacent
bis-THF ring acetogenin, were isolated from the stem bark of
Asimina triloba (L.)
Dunal (Annonaceae). Their structures were
established based on hemical and
spectral evidence. The relative stereochemistry of 1 was determined
as trans/threo/threo/trans/erythro from C-10
to C-22 by comparisons of NMR data with
those of model compounds. Compound 1 is the first example of a nonadjacent
bis-THF acetogenin being isolated from the
title species and represents a new type
of these compounds. Bioactivities of these new structures against
brine shrimp larvae and six
human solid tumor cell lines were determined, and cytotoxic
selectivities were shown for the lung (A-549) and breast (MCF-7)
cel lines with up
to a million times the potency of adriamycin. " copy
9113328 then click PMID
and paste the number in their search box
20:
"Two
novel bioactive ketolactone Annonaceous acetogenins, (2,4-cis)-asimicinone
(1) and (2,4-trans)-asimicinone (2),
have been isolated from Asimina triloba (Annonaceae) by bioactivity directed
fractionation. The separation of these two epimeric
compounds was achieved by HPLC methods using a Si gel normal phase
column eluted with acetone in hexane gradients.
The assignments of cis or trans stereochemistry
of the ketolactone moieties were made on the bases of 1H-1H COSY
and NOESY experiments. 1 and 2 showed
selective cytotoxicities against A-549 (human
lung cancer) and MCF-7 (human breast cancer) cell lines with ED50
values as low as
< 10(-7) micrograms/ml with 2 being the more active isomer."
copy 8743934 then click PMID
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21:
Purdue University
" The cell inhibition activities of several
Annonaceous acetogenins, covering the three
major structural classes of bis-adjacent, bis-non-adjacent, and
single tetrahydrofuran (THF) ring
compounds and their respective ketolactone rearrangement
products, were tested in an in vitro disk diffusion assay against
three murine (P388, PO3, and M17/Adr) and
two human (H8 and H125) cancerous cell lines
as well as a non-cancerous immortalized rat GI epithelial cell line
(I18). The
results demonstrate a dose-dependent inhibition of cancerous cell
growth, while non-cancerous
cell growth is not inhibited by the same dosages. All of the
acetogenins, irrespective of
their various structural types, inhibit the growth of
adriamycin resistant tumor cells and non-resistant tumor cells at
the same levels of
potency. These results show that the Annonaceous acetogenins are
an extremely potent
class of compounds, and their inhibition of cell growth can be
selective for cancerous cells
and also effective for drug resistant cancer cells,
while exhibiting only minimal toxicity to 'normal' non-cancerous
cells." copy 7553608
then click PMID
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22:
Purdue University "Longicin
[1] and (2,4-cis and trans)-goniothalamicinone [2], two new
monotetrahydrofuran Annonaceous acetogenins,
have been isolated from the leaves and
twigs of Asimina longifolia (the long leaf paw paw) by the use of
the brine shrimp lethality test
for bioactivity-directed fractionation. The structures
were elucidated based on spectroscopic and
chemical methods. Compound 1 was converted
to its ketolactone isomer, (2,4-cis and trans)-longicinone [3],
to aid the stereochemical elucidation
of 1. Compounds 1-3 showed selective and potent
cytotoxicities to certain human
tumor cell lines, with the potency of 1 against pancreatic
carcinoma (PaCa-2) over one million times that of adriamycin. Nine known cytotoxic acetogenins,
annonacin, xylomaticin, isoannonacin, gigantetrocins
A and B, muricatetrocins A and B, gigantetrocin-A-one and
goniothalamicin, were also isolated
for the first time from this species." copy 7494147
then click PMID
and paste the number in their search box
23: Hopital
de la Salpetriere, Paris, France.
"In Guadeloupe, epidemiological
data have linked atypical parkinsonism with fruit and
herbal teas from plants of the Annonaceae family, particularly Annona
muricata. These plants contain a class
of powerful, lipophilic complex I inhibitors,
the annonaceous acetogenins. To determine
the neurotoxic potential of these
substances, we administered annonacin, the major acetogenin of
A. muricata, to rats intravenously
with Azlet osmotic minipumps (3.8 and 7.6 mg per kg
per day for 28 days). Annonacin inhibited
complex I in brain homogenates in a concentration-dependent
manner, and, when administered systemically, entered the
brain parenchyma, where it was detected by
matrix-associated laser desorption ionization-time
of flight mass spectrometry, and decreased brain ATP levels by
44%. In the absence of evident systemic toxicity,
we observed neuropathological abnormalities
in the basal ganglia and brainstem nuclei. Stereological cell
counts showed significant loss of dopaminergic
neurones in the substantia nigra (-31.7%),
and cholinergic (-37.9%) and dopamine and cyclic AMP-regulated
phosphoprotein (DARPP-32)-immunoreactive GABAergic
neurones (-39.3%) in the striatum,
accompanied by a significant increase in the number of astrocytes
(35.4%) and microglial cells (73.4%). The
distribution of the lesions was similar
to that in patients with atypical parkinsonism. These data are
compatible with the theory that annonaceous
acetogenins, such as annonacin, might
be implicated in the aetiology of Guadeloupean parkinsonism and
support the hypothesis that
some forms of parkinsonism might be induced by environmental
toxins."
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