Methanolic Extracts of Bitter Melon Inhibit Colon Cancer Stem Cells by Affecting Energy Homeostasis and Autophagy

Kwatra, Deep; Subramaniam, Dharmalingam; Ramamoorthy, Prabhu; Standing, David; Moran, Elizabeth; Ravichandiran, V.; Mitra, Ashim K.; Umar, Shahid; Anant, Shrikant

doi:10.1155/2013/702869

Cited by 60 publications

(57 citation statements)

References 44 publications

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“…Nakanishi et al (30) later demonstrated via a series of lineage-tracing experiments that Dclk1 + cells can act as the initiating cell for intestinal tumors in Apc Min/+ mice and proposed that Dclk1 may represent a marker for “tumor stem cells”. Importantly, these studies also demonstrated that genetic ablation of Dclk1 + cells dramatically reduced intestinal tumor burden, suggesting that Dclk1+ cells may provide a target for novel CRC therapies (30,51). Thus, the tumor protection afforded by dietary methyl donor restriction may be based in part on a selective reduction in Dclk1 + cell populations.…”

Section: Discussionmentioning

confidence: 82%

Dietary Methyl Donor Depletion Suppresses Intestinal Adenoma Development

Hanley

Kadaveru

Giardina

et al. 2016

Cancer Prevention Research

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The role of folate one-carbon metabolism in colorectal cancer development is controversial, with nutritional intervention studies producing conflicting results. It has been reported that ApcMin/+ mice maintained on a diet deficient in the methyl donors folic acid, methionine, choline and vitamin B12, and supplemented with homocysteine, show a >95% reduction in intestinal tumor development. The present study extends these findings and shows that tumor protection afforded by dietary methyl donor deficiency (MDD) is long-lasting. After eleven weeks of MDD, tumor protection persisted for at least an additional seven weeks of methyl donor repletion (22.2 ± 3.5 vs 70.2 ± 4.6 tumors per mouse; P<0.01). Sustained tumor protection was associated with a reduction in intestinal crypt length (26%, P<0.01), crypt cell division and crypt fission, and an increase in apoptosis of both normal crypts and tumors (4.9- and 3.2-fold, respectively, P<0.01). MDD also caused a significant reduction in the number of Dclk1-positive cells in the intestine (62%, P<0.01), a long-lived crypt cell with cancer stem cell potential. Several undesirable effects associated with methyl donor restriction (e.g., reduced body weight gain) were shown to be transient and readily reversible following methyl donor repletion. Taken together, these results indicate that even temporary dietary methyl donor restriction in adenoma-prone mice can induce persistent changes to the intestinal epithelium and provide long-lasting tumor protection. These data also suggest that transient reductions in dietary methyl donor consumption should be considered when studying the impact of folate on colon cancer risk in humans.

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Section: Discussionmentioning

confidence: 82%

Dietary Methyl Donor Depletion Suppresses Intestinal Adenoma Development

Hanley

Kadaveru

Giardina

et al. 2016

Cancer Prevention Research

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“…This may enhance the tolerance of cells located at the tumor core to hypoxia and nutritional deficiency, thus increasing their resistant to cell death (7). In certain cases, the upregulation of autophagy activity may protect colon cancer cells from harm due to chemotherapeutic drugs or selective cell death (20). Therefore, studying the changes in autophagy and autophagy-related genes at the molecular level is of significance to clarify the pathogenesis of colon cancer and identify therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

Wogonoside inhibits cell growth and induces mitochondrial-mediated autophagy-related apoptosis in human colon cancer cells through the PI3K/AKT/mTOR/p70S6K signaling pathway

et al. 2018

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Abstract. Wogonoside, the main effective constituent of traditional Chinese medicine Scutellaria, belongs to the glucuronide family, with various functions, including detoxification, anti-inflammation and nourishing gallbladder, lowering blood pressure, diuresis and anti-allergic reactions. However, the effects of wogonoside on human colon cancer cells remain unclear. The present study aimed to investigate the anticancer effect of wogonoside on human colon cancer cells in vitro and its anticancer mechanisms. The results demonstrated that wogonoside significantly inhibited cell growth, induced apoptosis and mitochondrial-mediated autophagy of colon cancer cells. Furthermore, the results revealed that wogonoside significantly increased caspase-3 and caspase-9 expression levels, induced apoptosis regulator Bax/Bcl-2 and microtubule-associated protein 1A/1B-light chain 3 protein expression, suppressed the phosphatidylinositol 3 kinase (PI3K)/RAC-α serine/threonine-protein kinase (Akt)/mechanistic target of rapamycin (mTOR)/p70 S6 kinase (p70S6K) signaling pathway and induced p62 protein expression in colon cancer cells. In conclusion, these results demonstrated that wogonoside inhibits cell growth and induces mitochondrial mediated autophagy-related apoptosis in human colon cancer cells through modulation of the PI3K/Akt/mTOR/p70S6K signaling pathway.

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“…Indian medicinal system is a source of such plant database [2] which either in the form of powder extracts, pills or liquid forms (solutions and suspensions) has been used widely in India for treatment of various diseases. The Indian medicinal plants described in Ayurveda such as bitter melon [3–4] , turmeric [5–6] , and bael [7–8] , have proven their importance in recent years for treatment of various diseases, including diabetes and cancer. The development of science and technology in recent time makes it possible to discover the active constituents present in these plants and establish their biological targets for evolving them as a remedy for treating diseases.…”

Section: Introductionmentioning

confidence: 99%

“…The treatment with whole MC fruit extract exerts a dose-dependent reduction in the number and size of colonospheres. The extracts also decrease the expression of Doublecortin-like kinase 1 (DCLK1) and Leucine-rich repeat-containing G-protein coupled receptor 5 ( LGR5 ) [4] . In addition, further study from our lab has determined effects of MC extract on anti-cancer activity and bioavailability of doxorubicin (DOX) in colon cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Bitter melon: a panacea for inflammation and cancer

Dandawate

Subramaniam

Padhyé³

et al. 2016

Chinese Journal of Natural Medicines

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105

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Nature is a rich source of medicinal plants and their products that are useful for treatment of various diseases and disorders. Momordica charantia, commonly known as bitter melon or bitter gourd, is one of such plants known for its biological activities used in traditional system of medicines. This plant is cultivated in all over the world, including tropical areas of Asia, Amazon, east Africa, and the Caribbean and used as a vegetable as well as folk medicine. All parts of the plant, including the fruit, are commonly consumed and cooked with different vegetables, stir-fried, stuffed or used in small quantities in soups or beans to give a slightly bitter flavor and taste. The plant is reported to possess anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, anti-bacterial, anti-obesity, and immunomodulatory activities. The plant extract inhibits cancer cell growth by inducing apoptosis, cell cycle arrest, autophagy and inhibiting cancer stem cells. The plant is rich in bioactive chemical constituents like cucurbitane type triterpenoids, triterpene glycosides, phenolic acids, flavonoids, essential oils, saponins, fatty acids, and proteins. Some of the isolated compounds (Kuguacin J, Karaviloside XI, Kuguaglycoside C, Momordicoside Q–U, Charantin, α-eleostearic acid) and proteins (α-Momorcharin, RNase MC2, MAP30) possess potent biological activity. In the present review, we are summarizing the anti-oxidant, anti-inflammatory, and anti-cancer activities of Momordica charantia along with a short account of important chemical constituents, providing a basis for establishing detail biological activities of the plant and developing novel drug molecules based on the active chemical constituents.

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Methanolic Extracts of Bitter Melon Inhibit Colon Cancer Stem Cells by Affecting Energy Homeostasis and Autophagy

Cited by 60 publications

References 44 publications

Dietary Methyl Donor Depletion Suppresses Intestinal Adenoma Development

Dietary Methyl Donor Depletion Suppresses Intestinal Adenoma Development

Wogonoside inhibits cell growth and induces mitochondrial-mediated autophagy-related apoptosis in human colon cancer cells through the PI3K/AKT/mTOR/p70S6K signaling pathway

Bitter melon: a panacea for inflammation and cancer

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