Potential role of genipin in cancer therapy

Shanmugam, Muthu K.; Shen, Hongyuan; Tang, Feng Ru; Arfuso, Frank; Rajesh, Mohanraj; Wang, Lingzhi; Kumar, Alan Prem; Bian, Jin-Song; Goh, Boon Cher; Bishayee, Anupam; Sethi, Gautam

doi:10.1016/j.phrs.2018.05.007

Cited by 104 publications

(64 citation statements)

References 80 publications

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“…Genipin is the iridoid mostly present in genipap reported in the literature. Studies reported bioactivities of genipin as anticancer [ 21 , 22 , 46 ], anti-inflammatory [ 27 , 47 ], immunomodulatory [ 18 , 24 ], choleretic [ 28 , 48 ], and antioxidant [ 18 , 25 ]. To our knowledge, this is the first report about genipin’s bioavailability, as we could identify it in urine samples.…”

Section: Discussionmentioning

confidence: 99%

“…Some iridoids from the genipap fruit have already been reported in the literature: genipin, genipic acid, genipinic acid, geniposidic acid, geniposide, genameside A, genameside B, genameside C, genameside D, genipin-gentiobioside, gardenoside, gardendiol, shanzhiside, deacetylasperulosidic methyl ester, genipacetal, genipaol, genipamide, caffeoylgeniposidic acid, p -coumaroylgeniposidic acid, feruloyl gardoside, scandoside methyl ester, gardoside, p -coumaroylgenipin gentiobioside, and feruloylgenipin gentiobioside [ 12 , 14 , 19 , 20 ]. In vitro and animal experiments have shown that these compounds exhibit biological effects such as anticancer [ 21 , 22 ], placental cell regulation [ 12 ], neuroprotective [ 23 ] immunomodulatory, antioxidant [ 24 , 25 ], anti-inflammatory [ 26 , 27 ], choleretic [ 28 ], hepatoprotective, and hypoglycemic [ 29 ]. This study explores human exposure to the genipap juice after a single shot of 500 mL.…”

Section: Introductionmentioning

confidence: 99%

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Main Human Urinary Metabolites after Genipap (Genipa americana L.) Juice Intake

et al. 2018

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Genipap (Genipa americana L.) is a native fruit from Amazonia that contains bioactive compounds with a wide range of bioactivities. However, the response to genipap juice ingestion in the human exposome has never been studied. To identify biomarkers of genipap exposure, the untargeted metabolomics approach in human urine was applied. Urine samples from 16 healthy male volunteers, before and after drinking genipap juice, were analyzed by liquid chromatography–high-resolution mass spectrometry. XCMS package was used for data processing in the R environment and t-tests were applied on log-transformed and Pareto-scaled data to select the significant metabolites. The principal component analysis (PCA) score plots showed a clear distinction between experimental groups. Thirty-three metabolites were putatively annotated and the most discriminant were mainly related to the metabolic pathways of iridoids and phenolic derivatives. For the first time, the bioavailability of genipap iridoids after human consumption is reported. Dihydroxyhydrocinnamic acid, (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate, hydroxyhydrocinnamic acid, genipic acid, 12-demethylated-8-hydroxygenipinic acid, 3(7)-dehydrogenipinic acid, genipic acid glucuronide, nonate, and 3,4-dihydroxyphenylacetate may be considered biomarkers of genipap consumption. Human exposure to genipap reveals the production of derivative forms of bioactive compounds such as genipic and genipinic acid. These findings suggest that genipap consumption triggers effects on metabolic signatures.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Main Human Urinary Metabolites after Genipap (Genipa americana L.) Juice Intake

et al. 2018

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“…Notwithstanding this observation, it should be mentioned that genipin is known to have other effects than UCP2 inhibition. This includes anti-proliferative actions on tumor cells (37). Genipin has also been shown to be a water soluble crosslinking agent (38).…”

Section: Discussionmentioning

confidence: 99%

Isothermal Microcalorimetry of Tumor Cells: Enhanced Thermogenesis by Metastatic Cells

et al. 2019

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Tumor cells exhibit rewired metabolism. We carried out comparative analyses attempting to investigate whether metabolic reprograming could be measured by isothermal microcalorimetry. Intact metastatic cell lines of tongue cell carcinoma, human and murine melanoma, lung, and breast tumors consistently released more heat than nonmetastatic cells or cells displaying lower metastatic potential. In tongue squamous carcinoma cells mitochondrial enriched extract reproduced the heat release pattern of intact cells. Cytochalasin D, an actin filament inhibitor, and suppression of metastasis marker Melanoma associated gene 10 (MAGEA10) decreased heat release. Uncoupling protein 2 was highly expressed in metastatic cells, but not in non-metastatic cells. Carnitine palmitoyl transferase-1 inhibitor, Etomoxir strongly inhibited heat release by metastatic cells, thus linking lipid metabolism to thermogenesis. We propose that heat release may be a quantifiable trait of the metastatic process.

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“…UCP2 inhibition by genipin ( 55 ) promotes an increase in ROS, triggers the nuclear translocation of glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH), formation of autophagosomes and expression of LC3-II autophagy marker, leading to cell death or growth inhibition, invasion and migration of tumor cells. In addition, genipin ( 55 ) enhances autophagic cell death induced by gemcitabine, a clinically used chemotherapeutic agent ( Figure 5 ) [ 163 , 164 ].…”

Section: Rubiaceae Familymentioning

confidence: 99%

Ethnopharmacology of Fruit Plants: A Literature Review on the Toxicological, Phytochemical, Cultural Aspects, and a Mechanistic Approach to the Pharmacological Effects of Four Widely Used Species

et al. 2020

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Fruit plants have been widely used by the population as a source of food, income and in the treatment of various diseases due to their nutritional and pharmacological properties. The aim of this study was to review information from the most current research about the phytochemical composition, biological and toxicological properties of four fruit species widely used by the world population in order to support the safe medicinal use of these species and encourage further studies on their therapeutic properties. The reviewed species are: Talisia esculenta, Brosimum gaudichaudii, Genipa americana, and Bromelia antiacantha. The review presents the botanical description of these species, their geographical distribution, forms of use in popular medicine, phytochemical studies and molecules isolated from different plant organs. The description of the pharmacological mechanism of action of secondary metabolites isolated from these species was detailed and toxicity studies related to them were reviewed. The present study demonstrates the significant concentration of phenolic compounds in these species and their anti-inflammatory, anti-tumor, photosensitizing properties, among others. Such species provide important molecules with pharmacological activity that serve as raw materials for the development of new drugs, making further studies necessary to elucidate mechanisms of action not yet understood and prove the safety for use in humans.

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Potential role of genipin in cancer therapy

Cited by 104 publications

References 80 publications

Main Human Urinary Metabolites after Genipap (Genipa americana L.) Juice Intake

Main Human Urinary Metabolites after Genipap (Genipa americana L.) Juice Intake

Isothermal Microcalorimetry of Tumor Cells: Enhanced Thermogenesis by Metastatic Cells

Ethnopharmacology of Fruit Plants: A Literature Review on the Toxicological, Phytochemical, Cultural Aspects, and a Mechanistic Approach to the Pharmacological Effects of Four Widely Used Species

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