New anti-proliferative agent, MK615, from Japanese apricot “<i>Prunus mume</i>” induces striking autophagy in colon cancer cells <i>in vitro</i>

Mori, Satoshi; Sawada, Tokihiko; Okada, Toshie; Ohsawa, Tatsushi; Adachi, Masakazu; Kubota, Keiichi

doi:10.3748/wjg.v13.i48.6512

Cited by 25 publications

(33 citation statements)

References 29 publications

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“…Previous studies have revealed that MK615 has anti-neoplastic effects against gastric cancer [1] , breast cancer [2] , hepatocellular carcinoma [3] , and colon cancer [4] . The mechanisms responsible for the anti-neoplastic effect of MK615 include induction of apoptosis [1,2] and autophagy [4] , and suppression of Aurora A kinase [3] in cancer cells. However, the entire mechanisms of the anti-neoplastic effects of MK615 have not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B kinases

Okada¹,

Sawada²,

Osawa³

et al. 2008

WJG

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Section: Introductionmentioning

confidence: 99%

MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B kinases

Okada¹,

Sawada²,

Osawa³

et al. 2008

WJG

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“…the extract of ume has been reported to exert anticancer effects against gastric (3), breast (7), hepatocellular (8), colon (9) and pancreatic cancers (10). the mechanisms underlying these effects include the induction of apoptosis (3,7) and autophagy (9) and the suppression of aurora a kinase (8,10) in cancer cells.…”

mentioning

confidence: 99%

Advanced malignant melanoma responds to Prunus mume Sieb. Et Zucc (Ume) extract: Case report and in vitro study

Matsushita

Tada²,

Kikuchi³

et al. 2010

Experimental and Therapeutic Medicine

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Abstract. malignant melanoma (mm) is an aggressive chemoresistant skin cancer characterized by rapid metastasis and a poor prognosis. therefore, the development of innovative effective therapies is critical. mK615 is an extract from the Japanese apricot Prunus mume Sieb. Et Zucc (ume). at a neutral ph, it contains natural chemical substances such as triterpenoids that exert anti-neoplastic effects in several types of cancers. We found that in patients with advanced mm, mK615 dramatically suppressed the cutaneous in-transit metastasis of the disease. pre-and post-treatment comparison of tumors showed that the apoptotic index was significantly increased by MK615. In vitro studies, MTT assay, flow cytometric cell cycle analysis and immunofluorescence microscopy revealed that MK615 inhibited the growth of SK-mEl28 cells in a dose-dependent manner, increased the proportion of cells in sub-G1 phase and induced apoptosis. We further examined the expression of the receptor for advanced glycation end products (raGE). raGE is a multi-ligand receptor that binds to a novel cytokine, high mobility group box protein 1 (hmGB1), as well as advanced glycation end products. there is evidence that raGE/hmGB1 interactions enhance cell invasion in mm. here, we present Western blotting and immunofluorescence microscopy data indicating that mK615 inhibited the expression of raGE in SK-mEl28 cells, and suppressed the release of hmGB1 by SK-MEL28 cells. Our findings suggest that MK615 may be a valuable tool for treating mm and other malignant tumors.

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“…From ancient times, various parts of P. mume have been used as a health food and a medicinal agent for the treatment of fever, cough, and intestinal disorders. In addition, recent studies have reported that P. mume possesses various pharmacological activities, including inhibition of influenza A virus and motility of Helicobacter pylori, potential sources of free radical scavengers, improvement of blood fluidity, anti-inflammation, and anti-cancer action (21)(22)(23)(24)(25)(26)(27)(28). However, the cellular and molecular mechanisms responsible for the apoptotic effects of P. mume have not yet been determined in human cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have suggested that P. mume exerts a wide array of pharmacological and biological activities, such as potential sources of free radical scavengers, inhibition of influenza A virus, inhibition of the motility of Helicobacter pylori, improvement of blood fluidity, and inhibition of pro-inflammatory mediators (20)(21)(22)(23)(24)(25). In addition, P. mume has been known to exert anticancer activities in several types of human cancer cells (26)(27)(28). However, cellular and molecular mechanisms underlying the anti-cancer effects of P. mume are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis by ethanol extract of Prunus mume in U937 human leukemia cells through activation of caspases

Park

Jin²,

Kim³

et al. 2011

Oncol Rep

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Abstract. Prunus mume (P. mume), a traditional drug and health food in Korea, Japan and China, possesses various pharmacological activities that include a potential source of free radical scavenging, anti-viral, anti-microbial, antiinflammatory and anti-cancer activities. However, the cellular and molecular mechanisms of apoptosis induction by P. mume in human cancer cells are poorly understood. In the present study, we conducted an investigation of the pro-apoptotic effects of an ethanol extract of P. mume (EEPM) in U937 human leukemia cells. Exposure to EEPM was found to result in a concentration-dependent growth inhibition by induction of apoptosis. Induction of apoptotic cell death of U937 cells by EEPM showed a correlation with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family, including X-linked inhibitor of apoptosis protein (XIAP) and survivin, and anti-apoptotic Bcl-2, up-regulation of FasL, and cleavage of Bic. EEPM treatment induced proteolytic activation of caspase-3, -8 and -9, and degradation of caspase-3 substrate proteins, including poly(ADP-ribose) polymerase (PARP) and β-catenin. In addition, apoptotic cell death induced by EEPM was significantly inhibited by z-DEVD-fmk, a caspase-3-specific inhibitor, which demonstrated the important role played by caspase-3 in the process. Taken together, these findings suggest that EEPM may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells and that further studies are needed for the identification of the active compounds.

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New anti-proliferative agent, MK615, from Japanese apricot “Prunus mume” induces striking autophagy in colon cancer cells in vitro

Abstract: MK615 has an anti-neoplastic effect against colon cancer cells. The effect may be exerted by induction of apoptosis and autophagy.

Cited by 25 publications

References 29 publications

MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B kinases

MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B kinases

Advanced malignant melanoma responds to Prunus mume Sieb. Et Zucc (Ume) extract: Case report and in vitro study

Induction of apoptosis by ethanol extract of Prunus mume in U937 human leukemia cells through activation of caspases

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