New anti-proliferative agent, MK615, from J apanese apricot
“Prunus mume ” induces striking autophagy in colon cancer
cells in vitro
Shozo Mori, Tokihiko Sawada, Toshie Okada, Tatsushi Ohsawa, Masakazu Adachi, Kubota Keiichi
Shozo Mori, Tokihiko Sawada, Toshie Okada, Kubota Keiichi,
Second Department of Surgery, Dokkyo University School
of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi
Tatsushi Ohsawa, Masakazu Adachi, Japan Apricot Co., Ltd.,
Midori-cho 1-11-7, Takasaki, Gunma 370-0073, Japan
Correspondence to: Tokihiko Sawada, MD, PhD, Second
Department of Surgery, Dokkyo University School of Medicine,
Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293,
Telephone: +81-282-861111 Fax: +81-282-866317
Received: April 9, 2007 Revised: August 27, 2007
AIM: To investigate the anti-neoplastic effects of MK615,
an extract from the Japanese apricot (Prunus mume),
against colon cancer cells.
METHODS: Three colon cancer cell lines, SW480, COLO,
and WiDr, were cultured with MK615. Growth inhibition
was evaluated by cell proliferation assay and killing
activity was determined by lactate dehydrogenase assay.
Induction of apoptosis was evaluated by annexin Ⅴ
fl ow cytometry. Morphological changes were studied by
light and electron microscopy, and immunofl uorescence
staining with Atg8.
RESULTS: MK615 inhibited growth and lysed SW480,
COLO and WiDr cells in a dose-dependent manner.
Annexin Ⅴ fl ow cytometry showed that MK615 induced
apoptosis after 6 h incubation, at which point the
occurrence of apoptotic cells was 68.0%, 65.7% and
64.7% for SW480, COLO, and WiDr cells, respectively.
Light and electron microscopy, and immunofl uorescence
staining with Atg8 revealed that MK615 induced massive
cytoplasmic vacuoles (autophagosomes) in all three cell
CONCLUSION: MK615 has an anti-neoplastic effect
against colon cancer cells. The effect may be exerted by
induction of apoptosis and autophagy.
© 2007 WJG. All rights reserved.
Key words: Colon cancer; Japanese apricot; Prunus
mume; Autophagy; Apoptosis; MK615
Mori S, Sawada T, Okada T, Ohsawa T, Adachi M, Keiichi K.
New anti-proliferative agent, MK615, from Japanese apricot
“Prunus mume” induces striking autophagy in colon cancer
cells in vitro. World J Gastroenterol 2007; 13(48): 6512-6517
Japanese apricot, Prunus mume Sieb. et Zucc. (known as ume
in Japanese), has for centuries been a traditional Japanese
medicine, and is a familiar and commonly consumed
food. Prunus mume is a species of Asian plum of the
family Rosaceae. It is often called a plum, but it is more
closely related to the apricot (ume in Japanese). MK615,
an extract of compounds from Japanese apricot, has been
shown to possess an anti-proliferative effect against some
cancer cell lines[1,2]. Although MK615 induces apoptosis
of breast cancer cells and some other human cancer
cells, morphological studies have revealed the appearance
of abundant cytoplasmic vacuoles early after MK615
exposure, which are not relevant to apoptosis. The
precise role of these vacuoles has not been elucidated.
Even though effective chemotherapeutic agents
and regimens have been developed, colorectal cancer
is still associated with high rates of morbidity and
mortality worldwide[3,4]. Furthermore, the side effects
of chemotherapeutic agents often hamper the quality
of life of patients with colorectal cancer. There is a
need, therefore, to develop new, effective and less toxic
chemotherapeutic agents against colorectal cancer.
In the present study, we investigated the antineoplastic
effects of MK615 against colon cancer cell lines in vitro.
We found that MK615 strongly induced autophagy in
colon cancer cells and exerted antineoplastic effects.
MATERIALS AND METHODS
MK615, derived from the fruit of the Japanese apricot,
was provided by the Japan Apricot Co. (Gunma, Japan).
The preparation involved the extraction of apricot juice
using a press. This was then heated and concentrated.
The concentrate was dissolved in diethylether, which
was then completely removed from the extract by rotary
evaporation. The dried hydrophobic extract, MK615,
was dissolved in dimethyl sulfoxide (DMSO; Wako Pure
Chemical Industry, Osaka, Japan) at several concentrations.
Online Submissions: wjg.wjgnet.com World J Gastroenterol 2007 December 28; 13(48): 6512-6517
www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327
email@example.com © 2007 WJG. All rights reserved.
Japanese apricot, Prunus mume Sieb. et Zucc (ume in Japanese), has for
centuries been a traditional Japanese m edicine, and is a fam iliar and com m only
consumed food. Some components of Japanese apricot have been shown to
inhibit cancer cell growth.
MK615 is an extract of com pounds from Japanese apricot, and has been shown to
possess an anti-proliferative effect against som e cancer cell lines. Autophagy is a
form of PCD and has been shown to regulate cancer-cell growth. However, there
are not m any substances that can stably induce autophagy in cancer cells.
Innovations and breakthroughs
In this report, we clearly described that MK615 inhibited the growth of colon cancer
cells by aggressively inducing autophagy.
The side effects of chemotherapeutic agents often reduce the quality of life of
patients with colorectal cancer. MK615 appears to be an effective and less toxic
chem otherapeutic agent against colorectal cancer.
Autophagy is classifi ed as type Ⅱ PCD, and differs from typeⅠPCD (apoptosis).
Autophagy is a form of caspase-independent cell death, displays no DNA-
laddering, and is typically characterized by form ation of cytoplasm ic vacuoles. In
recent years, the im portance of autophagy has been stressed in various biological
fi elds, including cancer.
In this in vitro study, the authors investigated the antineoplastic effects of MK615, an
extract from Japanese apricot (um e in Japanese), against colon cancer cells. They
concluded that MK615 had an antineoplastic effect against colon cancer cells, and
the effect m ay have been exerted by induction of apoptosis and autophagy.
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