In peroxidation. An AGE annomuricin E was found

In a study performed by Jaramillo MC et al.,
the mechanism of action of ethyl acetate extract
of A. muricata leaves against colon cancer cells (HT-29 and
HCT-116) and lung cancer cells (A549) has been illustrated. The leaf extract
was proficient to induce apoptosis in colon and lung cancer cells through the
mitochondrial-mediated pathway. This anti-proliferative effect was alongside
with cell cycle arrest in the G1 phase (20). However, the
migration and invasion of colon cancer cells were profoundly inhibited by the
leaf extract. The in vivo chemo
preventive potential of the ethyl acetate extract of the A. muricata leaves
against azoxymethane-induced colonic aberrant crypt foci (ACF) in rats was validated
by Moghadamtousi and colleagues. Oral dosage that was administered for 60days
caused a significant reduction of ACF formation in rats when tested by
methylene blue staining of the colorectal specimens. PCNA and Bcl2 proteins
were down regulated whereas Bax protein was up regulated after the administration
of the extract. This was depicted in the immunohistochemistry
analysis where they were compared with cancer control group. In addition the
levels of enzymatic antioxidants showed an increase and a suppression was seen
in malondialdehyde level of the colon tissue homogenates. This suggested the restraint
of lipid peroxidation. An AGE annomuricin E was found to inhibit the growth of
HT-29 cells. The cytotoxic effect of annomuricin E was enhanced by the G1 cell cycle
arrest. Annomuricin activated the mitochondrial events comprising the
dissipation of the mitochondrial membrane potential and caused the leakage of
cytochrome c from the mitochondria. Followed by this, annomuricin E activated
caspase 3/7 and caspase 9 responsible for the apoptosis. Furthermore, Moghadamtousi and colleagues examined that
ethyl acetate extract of Annona muricata leaves (EEAM) exerted a
striking cytotoxic effects on HCT-116 cells as determined by MTT and LDH
assays. Flow cytometric analysis illucidated the cell cycle arrest at G1 phase
and also the externalization of phosphatidylserine acting as an indicator of
the induction of apoptosis. EEAM treatment activated excessive accumulation of
ROS followed by disruption of MMP, cytochrome c leakage and
activation of the initiator and executioner caspases in both colon cancer cells.
These processes subsequently steer to attenuation of
mitochondrial membrane potential (MMP) and cytochrome c release. Release of
cytochrome c activates apotosome and the intrinsic caspase cascade that
triggers execution of apoptosis through DNA fragmentation. Immunofluorescence analysis portrayed the
up-regulation of Bax and down-regulation of Bcl-2 proteins while treated with
EEAM. Furthermore, EEAM conspicuously blocked the migration and invasion of
HT-29 and HCT-116 cells. (29,30,31).