Saturday, 3 February 2018

Eggplants: The NightShade Vegetable in Cancer Risks

Kyle J. Norton

Eggplant is a species of S. Melongena with deeply purple color, belongings to the family Solanaceae and native to India, cultivated in southern and eastern Asia since prehistory.

Nutrients
1. Carbohydrates
2. Sugars
3. Fiber
4. Fat
5. Protein
6. Thiamine (Vitamin B1)
7. Riboflavin (Vitamin B2)
8. Niacin (Vitamin B3)
9. Pantothenic acid (B5)
10. Vitamin B6
11. Folate (Vitamin B9)
12. Vitamin C
13. Tryptophan
14. Manganese
15. Calcium
16. Copper
17. Iron
18. Magnesium
19. Phosphorus
20. Potassium
21. Zinc
22. Etc.

Chemical constituents
The vegetable chemical compounds containing include sterols (i.e. typical plant sterols, androstane, pregnane and cholestane derivatives, steroidal alkaloids and sapogenins), phytosterols, triterpenes, δ-amyrin, Chlorogenic acid, Nasunin and other Polyphenolic compounds.

Cancer is a class of diseases characterized by cell growth irregularly and disorderly in the tissue and organs. At the late stage, the cells may spread a distance away to infect other healthy tissue and organs.

Accordingly to statistic, 30% of all deaths in Canada are resulted from cancer.

Epidemiological studies suggested that eggplant have a profound and sustainable effect in reduced risk and treatment of various types of cancer through its bioactive phytochemicals, including t glycoalkaloids for antiproliferative activities against human colon (HT29) and liver (HepG2) cancer cells(1); delphinidin, a flavonoid pigment contained in the peel of eggplant in human fibrosarcoma HT-1080 cell(2).

1. Colon Cancer
Conon cancer is medical condition characterized by irregular cell growth in the issues of colon At the later stage, the cancerous cell may invade other healthy tissues and organs a distance away drom the original site.

According to statistic, approximately 4.3 percent of men and women will be diagnosed with colorectal cancer at some points during their lifetime.

In human colon (HT29), observed microculture tetrazolium (MTT) assay, application of several chemical constituents isolated from eggplant(2)(5), including glycoalkaloids solamargine and solasonine and their common aglycon solasodine; and the nonsteroidal alkaloid jervine, demonstrated a overwhelming effect in inhibited colon cancer cell proliferation(3), particularly in the compound glycoalkaloids in compared to others in dose-dependent manner.

Further analysis also suggested that the nitrogen-containing secondary plant metabolites glycoalkaloids anti colon cancer cells expression was attributed to its derivative α-solamargine and α-solasonine activities(3) in inhibited the growth of the cells in culture (in vitro) and tumor growth in vivo.

Additionally, in HT-29 and HCT-116 cell lines, anthocyanins isolated from eggplant displayed a substantial antioxidant effect in inhibited reactive oxygen species(ROS) expression(4) in induction of healthy cellular DNA damage through increased production of inflammatory cytokines(4).

In compared to anthocyanins, administration of nasunin with glycosylation on C3 and C5 and an acyl group (p-coumaric acid) derivatives demonstrated the least effect on ROS reduction but exhibited ROS over expression in induction of cytotoxicity in colon cell lines(4), thus ameliorating tumor proliferation and site expansion.

Nasunin and its deacylated derivatives protected healthy cells from DNA damage in a dose-dependent manner(4), although with lesser anti ROS properties.

Dr. Pu Jing(4), the lead author said, "anthocyanins isolated from Chinese eggplant var. Niu Jiao Qie and other delphinidin have antioxidant activities in colon cancer cells and also protect cells from DNA damage".

The evaluation of anthocyanins chemopreventive properties in 25 colon cancer patients confirmed that application, containing 0.5-2.0 grams anthocyanins showed a strong effect in increased anthocyanin concentrations in plasma and urine, reaching approximately 179 ng/gram in tumor tissue at the highest dose(6), that indicated the phytochemical anthocyanins and their degradation products have reached the colon intact.

Examined tumor tissue from all patients also found that the rate of cancer cells proliferation was also decreased by 7% in compared to pre-intervention value and application in dose dependent also inhibited the expression of insulin-like growth factor 1 concentrations(6) in stimulates growth in cancer cells throughout the colon tumor site.

Dr. Thomasset S(6), the lead auhtor in the study of "Intact anthocyanins and metabolites in rat urine and plasma after 3 months of anthocyanin supplementation" said, "Studies of doses containing <0.5 gram of bilberry anthocyanins are necessary to adjudge whether they may be appropriate for development as colorectal cancer chemopreventive agents".


2. Melanoma 
Melanoma is medical condition characterized by irregular cell growth in the issues of skin. At the later stage, the cancerous cell may travel a distance away to invade other healthy tissues and organs.

According to statistic, approximately 87,110 new cases of invasive melanoma caner will be diagnosed in the U.S. in 2017.

The investigated the glycoalkaloids isolated from numerous Solanaceous plants, including eggplant in risk of melanoma, suggested that eggplant glycoalkaloids derivatives α-solamargine and α-solasonine(5) demonstrated a significant effect in inhibition of cancer cells proliferation, in both vitro and vivo.

Further analysis of the chemistry and structure-activity also suggested that both α-solamargine and α-solasonine exert a strong antioxidant effect in increased cancer cell apoptosis and decrease tumor formation through expression of mitogen-activated protein kinase (MAPK)(5) in cancer cellular processes and NF-kappaB cascades(5) in enhanced T-cell development, maturation, and proliferation, in animal models.

In melanoma cell lines, application of glycoalkaloid solamargine showed a complete
inhibition of the growth of metastatic and primary melanoma cell lines WM239 and WM115 with minimum effect on normal and benign WM35 melanoma cells through reduced blood supplies in induced necrosis(9) by rapid induction of lysosomal membrane permeabilization in controls the passage to allow intracellular or intraorganellar antigens into and out of lysosomes.

The action of glycoalkaloid solamargine in exhibition of cancer cell apoptosis was found to attribute to the physiological processes activated by cathepsin B activity in triggering the extrinsic mitochondrial death pathway through releasing cytochrome c, a hemeprotein(9) found loosely in the inner membrane of the mitochondrion and tumor necrosis factor receptor 1(TNFR1)(9) in expression of the transcription factor NF-κB in mediated apoptosis.

In the intrinsic apoptosis pathway, Solamargine disrupted the function of hILP/XIAP in blocking cancer cells apoptosis through an interaction with TRAF protein activated by mediating activation of transcription factors of the NF-κB(9), thus improving caspase-3 cleavage in the execution-phase of cell apoptosis, up regulating Bcl-xL, and Bcl2 in regulated apoptosis, cell cycle arrest and cell cycle entry and suppressing apoptotic peptidase activating factor 1 Apaf-1 and Bax family in expression of both anti- or pro-apoptotic regulation(9).

Dr. Al Sinani SS, the lead author, after taking into account of other con founders said, " Solamargine showed high efficacy in vitro particularly against the vertical growth phase melanoma cells" and "is a promising anti-malignant melanoma drug".

In the researching of chemically isolate and explore an antimelanogenesis inducer in extracts of Solanum melongena L. "Usukawamarunasu" eggplant, the identified dioscin ([25R]-Spirost-5-en-3β-yl) 2-O-(6-deoxy-α-L-mannopyranosyl) - 4-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranoside] displayed an overwhelming effect in inhibition of α-melanocyte-stimulating hormone (MSH)-induced melanogenesis in B16 murine melanoma cells(8).

According to the immunoblot analysis, dioscin prevented B16 murine melanoma cells proliferation was found to attribute to ameliorate the expression of tyrosinase in intracellular production of melanin, tyrosinase-related protein-1 (TRP-1), and TRP-2(9) which were significantly correlate to tumor cell stage and grade and metastasis-free survival (DMFS), overall survival.
Additionally, the suppression of tyrosinase, TRP-1, and TRP-2 expression also attenuated
alpha-melanocyte-stimulating hormone in production of melanogenesis in B16 cells(9).

Further differentiation also indicated that, the identified chemicals also exerted anti melanoma cells preoperative effect through mediating pro-survival functions microphthalmia-associated transcription factor (MITF)(9), through inhibition of Cyclic AMP-responsive element-binding protein (CREB) in express a cassette of regeneration-associated genes with alternated DNA transcription caused by phosphorylation in expression of α-MSH-induced melanogenesis in B16 cells(9).


3. Liver cancer
Liver cancer is medical condition characterized by irregular cell growth in the issues of liver. At the later stage, the cancerous cell may travel a distance away to invade other healthy tissue and organs.

According to statistic, approximately 40,710 new cases (29,200 in men and 11,510 in women) of liver cancer and and intrahepatic bile duct cancer will be diagnosed in US 2017.

Glycoalkaloids (α-solamargine and α-solasonine), nitrogen-containing secondary plant metabolites found in eggplants and numerous Solanaceous plants including potatoes, and tomatoes expressed a strong inhibition of the growth of the liver tumor cells in culture and tumor growth in vivo(10)(11).

More specifically, α-solamargine and α-solasonine induced apoptosis in cancer cells but not normal cells through functions in eliminated old cells, unnecessary cells, unhealthy cells and cancer cells without causing harm to healthy cells in the surrounding area(5).

 α-solamargine also suppressed liver cancer cell proliferation and induced apoptosis through cell cycle arrest(5).

Additionally, in HCT-116 cell line, anthocyanins isolated from eggplant displayed a substantial antioxidant effect in inhibited reactive oxygen species(ROS) expression in promoting oxidative stress and cytotoxicity(6)(120 in induction of healthy cellular DNA damage in initiated early onset of liver cancer.

In compared to anthocyanins, administration of nasunin with glycosylation on C3 and C5 and an acyl group (p-coumaric acid) derivatives demonstrated the least effect on ROS reduction(6)(12) but exhibited ROS over expression in induction of cytotoxicity in colon cell lines, thus ameliorating tumor proliferation and site expansion(6), according to microculture tetrazolium (MTT) assay.

Further analysis, also indicated that nasunin and its deacylated derivatives protected healthy cells from DNA damage through antioxidant capacity in a dose-dependent manner.

In the valuations carried out with four concentrations each (0.1, 1, 10, and 100 microg/mL) of the the potato trisaccharide glycoalkaloids alpha-chaconine and alpha-solanine; the disaccharides beta(1)-chaconine, beta(2)-chaconine, and beta(2)-solanine; the monosaccharide gamma-chaconine and their common aglycon solanidine; the tetrasaccharide potato glycoalkaloid dehydrocommersonine; the potato aglycon demissidine; the tetrasaccharide tomato glycoalkaloid alpha-tomatine, the trisaccharide beta(1)-tomatine, the disaccharide gamma-tomatine, the monosaccharide delta-tomtine, and their common aglycon tomatidine, and the eggplant glycoalkaloids solamargine and solasonine and their common aglycon solasodine; and the nonsteroidal alkaloid jervine, researchers found that the glycoalkaloids isolated from all vegetables demonstrated as the most active compound in inhibited liver cancer in compared to colon cells(1).

In compared to anticancer drugs doxorubicin and camptothecin, all isolated compounds also exerted significant activity in decreased cancer cell proliferation and induced apoptosis in concentration dependent manner.


4. Prostate cancer 
Prostate cancer is medical condition characterized by irregular cell growth in the issues of prostate. At the later stage, the cancerous cell may invade other healthy tissues and organs a distance away drom the original site.

According to statistic, approximately 11.6 percent of men will be diagnosed with prostate cancer at some point during their lifetime.

In vitro and in vivo application of glycoalkaloids derivatives α-solamargine and α-solasonine expressed a significant effect in inhibition of tumor formation and growth in fish and mice and human prostate cancer cell lines(1).

In deed, in the human prostate cancer cell PC-3. administration of non toxic dose of α-solanine initiated cancer suppression and reduced the viability of the human cancer cell through significantly elevated epithelial marker E-cadherin gene expression(13) in target mutated cell in induction of cell profileration and invasion and decreased mesenchymal marker vimentin expression in initiated cell metastasis.

 α-Solanine ameliorated cancer cell proliferation and tumor initiation through reduced mRNA level of matrix metalloproteinase-2 (MMP-2) and 9 (MMP-9)(13) in stimulated cancer invasion and metastasis and increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK)(13) in suppression of prostate tumor progression and tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in the regulation of MMP(3) activity, particular in induction of cancer cell over expression.

According to the observation of the Immunoblotting assays, injection of α-solanine is effective in suppressed phosphorylation of phosphatidylinositide-3 kinase (PI3K)(13) which plays an important role in modulated cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking involved cancer progression, Akt phosphorylates expression(13) with primary functions is to promote cell growth and protein synthesis and The extracellular signal-regulated kinase (ERK) signaling pathway phosphorylates(13) with function in the control of diverse cellular processes including such as proliferation, survival, differentiation and motility.

 α-solanine reduced levels of microRNA-21 (miR-21) in expression of cancer progression(13). Higher levels of miR-21 are correlated to more advanced malignancies and elevated tumor suppressor miR-138 expression in induced prostate cancer cells apoptosis through cell cycle arrest at G1/S transition(13).


5. Lung cancer
Lung cancer is medical condition characterized by irregular cell growth in the issues of lung At the later stage, the cancerous cell may invade other healthy tissues and organs a distance away from the original site.

According to statistic, approximately 28,600 Canadians will be diagnosed with lung cancer represented 14% of all new cancer cases in 2017.

In the investigation of the eggplant bioactive phytochemical glycoalkaloids activity and risk of various types of malignant tumors, Dr. Friedman M found that derivatives of glycoalkaloids, α-solamargine and α-solasonine(1) demonstrated a strong inhibited effect in the growth of the lung and other cancer cells in culture (in vitro) as well as tumor growth in vivo, involved some unknown signalling pathways(14).

The investigation of solasodine, a naturally occurring aglycone of glycoalkaloid in eggplant (Solanum melongena) in human lung cancer cell line A549 showed that solasodine displays a significant effect in ameliorated cancer cell viability and initiated cell apoptosis through attenuating expression of mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9(14) which were found to be elevated in patients with lung cancer in compared to healthy subjects and extracellular inducer of matrix metalloproteinase (EMMPRIN)(14), a cell surface glycoprotein which plays an important role in stimulated the production of several matrix metalloproteinases (MMPs).

Further investigation, also indicated that the inhibitory property of solasodine by increased the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK)(14) not only reduces risk of RECK accelerated cancer cell proliferation but also exhibits initiation of irreversible growth cycle arrest through short hairpin of mRNA in suppression of the RECK gene(14).

Additionally, injection of solasodine promoted cancer cells death was also associated to the over expression of tissue inhibitor of metalloproteinase-1 (TIMP-1)(14), a glycoprotein found in several tissues of organisms with function in involved in degradation of the extracellular matrix as mention above and TIMP-2(14), a member of the TIMP gene family with function as a metastasis suppressor.

According to the immunoblotting assays, administration of solasodine is very effective in suppressing PI3K /Akt phosphorylation of lung cancer cell of in induction of cell proliferation(13)(14).

PI3K /Akt phosphorylation plays critical roles in the regulation of many cellular processes including cell cycle, growth, apoptosis and signal transduction pathways.

Alterations in phosphorylation pathways result in serious outcomes in the form of diseases, especially cancer.

Solasodine decreased expression of microRNA-21 which has been found to be higher in more advanced malignancies, in initiated early entry phase of cancer developing by stimulated production of RECK(13)(14) in accelerated cancer cell proliferation, thus decreasing risk of cell invasion.

After taking into account of all con founders, Dr. Shen KH, the lead author said, "the findings demonstrate an attractive therapeutic potential for solasodine in lung cancer anti-metastatic therapy".

6. Bone Cancer
Bone cancer is medical condition characterized by irregular cell growth in the issues of colon At the later stage, the cancerous cell may invade other healthy tissues and organs a distance away drom the original site.

According to statistic, early stage of bone cancer diagnosis of 5-year survival rate are approximately 85%.

In the evaluation of the effect of solamargine, a steroidal glycoalkaloid against human osteosarcoma
U2OS cells, researchers at the Shandong University showed that application of solamargine exerted a substantially reduced cell viability and induced apoptosis in osteosarcoma U2OS cells through over expression of mRNA and protein expressions of p53 in regulated the cell cycle(15) in involvement of tumor suppression and Bax(15) in expression of a pro-apoptotic regulators involved in a wide variety of cellular activities and activated apoptosis and reduced expression of Bcl-2(15) with function against cell apoptosis.

Further analysis also indicated that solamargine induced apoptotic and suppressible activity against osteosarcoma U2OS cell line was attributed to increase mitochondrial translocation of p53(15), induction of cell death through modulated loss of mitochondrial membrane of cancer cells and cytochrome c release(15) during early stage of apoptosis.

Solamargine also activated the expression of caspase-9(15) which plays a central role of in apoptosis signal transduction, a cascade of biochemical reactions inside the cell in ignition of cell death and the regulation of cancer cell apoptosis and caspase -3, a caspase protein(15) that interacts with caspase-9 and dependent on mitochondrial cytochrome c release(15) in initiation of anti cell proliferation and tumor cell invasion.

Additional differentiation of the effect of p53, researchers found that although P53 may have a profound and positive inhibition of the tested cancer line, but its function also was reduced due to the presence of pifithrin-α(15), and mitochondrial translocation inhibitor pifithrin-μ(15), in inhibition of function of p53-mediated apoptosis, in prevented p53 binding to Bcl-xL and Bcl-2 (15)at the mitochondria ..., thus partially reversing the anti proliferative activity of solamargine.

Dr. Li X(15), the lead scientist said, "(the results finding, indicated that) Solamargine activates the mitochondria-mediated apoptotic pathway in U2OS cells via both p53 transcription-dependent and -independent mechanisms".

Although eggplant with abundantly bioactive compounds may be considered as function food in reduced risk and treatment of cancers, however, according to Dr. Shimada A. in an one year (continuous 2 days for 12 months) food surveys held at 5 areas in Japan, the frequency of intake eggplant may associate to increase risk of gastric cancer and gastric cancer mortality rate(7), but may account partly for the geographic variation in gastric cancer mortality in Japan(11).



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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)

Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

Sources
(1) Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells by Lee KR1, Kozukue N, Han JS, Park JH, Chang EY, Baek EJ, Chang JS, Friedman M.(PubMed)
(2) Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro by Nagase H1, Sasaki K, Kito H, Haga A, Sato T.(PubMed)
(3) Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells by Lee KR1, Kozukue N, Han JS, Park JH, Chang EY, Baek EJ, Chang JS, Friedman M.(PubMed)
(4) Effect of glycosylation patterns of Chinese eggplant anthocyanins and other derivatives on antioxidant effectiveness in human colon cell lines by Jing P1, Qian B2, Zhao S2, Qi X3, Ye L2, Mónica Giusti M4, Wang X5.(PubMed)
(5) Chemistry and anticarcinogenic mechanisms of glycoalkaloids produced by eggplants, potatoes, and tomatoes by Friedman M1(PubMed)
(6) Pilot study of oral anthocyanins for colorectal cancer chemoprevention by Thomasset S1, Berry DP, Cai H, West K, Marczylo TH, Marsden D, Brown K, Dennison A, Garcea G, Miller A, Hemingway D, Steward WP, Gescher AJ.(PubMed)
(7) [Regional differences in gastric cancer mortality and eating habits of people].[Article in Japanese]  by Shimada A.(PubMed)
(8) Dioscin Derived from Solanum melongena L. "Usukawamarunasu" Attenuates α-MSH-Induced Melanogenesis in B16 Murine Melanoma Cells via Downregulation of Phospho-CREB and MITF by Nishina A1, Ebina K1, Ukiya M1, Fukatsu M1, Koketsu M2, Ninomiya M2, Sato D3, Kimura H4.(PubMed)
(9) Solamargine triggers cellular necrosis selectively in different types of human melanoma cancercells through extrinsic lysosomal mitochondrial death pathway by Al Sinani SS1, Eltayeb EA1, Coomber BL2, Adham SA1.(PubMed)
(10) Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells by Lee KR1, Kozukue N, Han JS, Park JH, Chang EY, Baek EJ, Chang JS, Friedman M.(PubMed)
(11) Food consumption and gastric cancer mortality in five regions of Japan by Tsubono Y1, Kobayashi M, Tsugane S.(PubMed)
(12) Solasodine, Solamargine and Mixtures of Solasodine Rhamnosides: Pathway to Expansive Clinical Anticancer Therapies Bill E. Cham by International Journal of Clinical Medicine, 2017, 8, 692-713
(13) α-Solanine inhibits invasion of human prostate cancer cell by suppressing epithelial-mesenchymal transition and MMPs expression by Shen KH1, Liao AC2, Hung JH3, Lee WJ4, Hu KC5, Lin PT6, Liao RF7, Chen PS8.(PubMed)
(14) Solasodine inhibits invasion of human lung cancer cell through downregulation of miR-21 and MMPs expression by Shen KH1, Hung JH2, Chang CW2, Weng YT2, Wu MJ2, Chen PS3.(PubMed)
(15) Solamargine induces apoptosis associated with p53 transcription-dependent and transcription-independent pathways in human osteosarcoma U2OS cells by Li X1, Zhao Y, Wu WK, Liu S, Cui M, Lou H.(PubMed)



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