Anti-cancer effects of D-limonene – Science


“Chemoprevention and therapy of cancer by d-limonene. The naturally occurring monoterpene d-limonene has chemopreventive and chemotherapeutic activity… The complete regression of mammary carcinomas by limonene… The multiple antitumorigenic effects of limonene are attainable at a high therapeutic ratio, suggesting that limonene and related monoterpenes may be efficacious in the chemoprevention and chemotherapy of human malignancies.”

“D-Limonene: safety and clinical applications. D-limonene is one of the most common terpenes in nature…  D-limonene is listed in the Code of Federal Regulations as generally recognized as safe… D-limonene has well-established chemopreventive activity against many types of cancer.”

“Cancer Chemoprevention by Phytochemicals and their Related Compounds. Cancer chemoprevention by phytochemicals may be one of the most feasible approaches for cancer control… phytochemicals obtained from vegetables, fruits, spices, teas, herbs and medicinal plants… have been proven to suppress experimental carcinogenesis in various organs.”

“d-limonene, an anticarcinogenic terpene.”

“Limonene exerts antiproliferative effects and increases nitric oxide levels on a lymphoma cell line by dual mechanism of the ERK pathway: relationship with oxidative stress. D-limonene is a common monoterpene found in nature. Previously, it has been demonstrated that it has antiproliferative effects on a lymphoma cell line…

“Effect of D-limonene on immune response in BALB/c mice with lymphoma. The monoterpene D-limonene and its metabolites have been shown to exert chemopreventive and chemotherapeutic activities against different tumors in animal models and clinical trials… Our data suggest that in addition to reported properties, D-limonene modulates the immune response with significant potential for clinical application.”

“Limonene-induced regression of mammary carcinomas. Dietary administration of the monocyclic monoterpenoid d-limonene causes complete regression of both dimethylbenz[alpha]anthracene- and N-nitroso-N-methylurea-induced rat mammary carcinomas. Carcinomas regress when limonene is added to the diet… Its removal from the diet results in a significant number of tumor recurrences…  Monoterpenoids such as limonene represent a novel class of anticancer drugs with the potential to cause tumor regressions with limited toxicity.”

“d-Limonene inhibits N-nitrosobis(2-oxopropyl)amine induced hamster pancreatic carcinogenesis… quantitative histological analysis showed that prolonged treatment with d-limonene significantly reduced the number of pancreatic carcinomas…These findings indicate that d-limonene inhibits the development of pancreatic carcinoma…”

“Inhibition by D-limonene of gastric carcinogenesis induced by N-methyl-N’-nitro-N-nitrosoguanidine in Wistar rats… These findings indicate that limonene inhibits the development of gastric cancers through increased apoptosis and decreased DNA synthesis of gastric cancers…”

“Inhibition by d-limonene of experimental hepatocarcinogenesis in Sprague-Dawley rats does not involve p21(ras) plasma membrane association… These findings indicate that limonene inhibits hepatocarcinogenesis and suggest that this effect may be clearly related to its effect in inhibiting cell proliferation and in enhancing apoptosis…”

“Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by d-limonene… d-limonene has antiangiogenic and proapoptotic effects on gastric cancer, thereby inhibits tumor growth and metastasis.”

“D-limonene induces apoptosis of gastric cancer cells.”

“Apoptosis: programmed cell death at a molecular level.”

“d -Limonene sensitizes docetaxel-induced cytotoxicity in human prostate cancer cells: Generation of reactive oxygen species and induction of apoptosis…  Our results show, for the first time, that d -limonene enhanced the antitumor effect of docetaxel against prostate cancer cells without being toxic to normal prostate epithelial cells. The combined beneficial effect could be through the modulation of proteins involved in mitochondrial pathway of apoptosis. d -Limonene could be used as a potent non-toxic agent to improve the treatment outcome of hormone-refractory prostate cancer with docetaxel.”

“Induction of apoptosis by D-limonene is mediated by inactivation of Akt in LS174T human colon cancer cells. D-limonene is recognized as a potential chemotherapeutic agent… d-limonene induced apoptosis via the mitochondrial death pathway and the suppression of the PI3K/Akt pathway.”

“Induction of apoptosis by d-limonene is mediated by a caspase-dependent mitochondrial death pathway in human leukemia cells… anti-tumoral activity of d-limonene, a monocyclic monoterpene, in human leukemia cells… Our findings and data, all suggest that the mitochondrial death pathway is primarily involved in the development of d-limonene-induced apoptosis.”

“Effects of D-limonene on leukemia cells HL-60 and K562 in vitro… It is concluded that D-L can inhibit proliferation and induce apoptosis of HL-60 and K562 cells…”

“Proliferation inhibition and apoptosis induction of K562 cells by D-limonene… It is concluded that the D-limonene can inhibit proliferation of K562 cells in dose-dependent manner, cause cell detained at G1 phase and induce apoptosis of K562 cells.”

“Inhibition of tumor progression by naturally occurring terpenoids.”

“Effect of naturally occurring monoterpenes carvone, limonene and perillic acid in the inhibition of experimental lung metastasis induced by B16F-10 melanoma cells… These results indicate that limonene and perillic acid could inhibit the metastatic progression of B16F-10 melanoma cells…”

“Antitumorigenic effects of limonene and perillyl alcohol against pancreatic and breast cancer… Perillyl alcohol and d-limonene, a closely related dietary monoterpene, have chemotherapeutic activity against pancreatic, mammary, and prostatic tumors. In addition, perillyl alcohol, limonene, and other dietary monoterpenes have chemopreventive activity… Monoterpenes are effective, nontoxic dietary antitumor agents which act through a variety of mechanisms of action and hold promise as a novel class of antitumor drugs for human cancer.”

“Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee. D-Limonene is a natural monoterpene with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. A phase I clinical trial to assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in patients with advanced cancer was followed by a limited phase II evaluation in breast cancer…D-Limonene is well tolerated in cancer patients at doses which may have clinical activity. The favorable toxicity profile supports further clinical evaluation.”

“Human metabolism of the experimental cancer therapeutic agent d-limonene. d-Limonene has efficacy in preclinical models of breast cancer, causing > 80% of carcinomas to regress with little host toxicity… Limonene is metabolized by humans and rats in a similar manner. These observations and the high therapeutic ratio of limonene in the chemotherapy of rodent cancers suggest that limonene may be an efficacious chemotherapeutic agent for human malignancies.”

“Inhibition of DMBA-induced mammary cancer by the monoterpene d-limonene… In addition to inhibiting the appearance of mammary tumors, d-limonene was also found to cause the regression of frank mammary tumors. No toxicity was evident in these rats even at the highest d-limonene dose…”

“D-Limonene modulates inflammation, oxidative stress and Ras-ERK pathway to inhibit murine skin tumorigenesis. D-Limonene, a common monoterepene has been shown to have antiproliferative, apoptosis-inducing and chemopreventive effects…”

“Cancer Prevention by Natural Compounds.”

“Molecular targets of dietary agents for prevention and therapy of cancer… fruits and vegetables are recommended for prevention of cancer and other diseases… The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food.”

“”D-Limonene is one of the most important terpenes found in cannabis/hemp. It has shown significant anti-cancer properties in a number of studies.”… D-Limonene is thought to be responsible for much of the relaxing effects of smoked cannabis. These effects are often absent in refined cannabinoid extracts which have many of the elements of the plant removed…”While the cannabinoids are only to be found in marijuana / hemp, many of the terpenes are found in a wide variety of different plants. The D-limonene in Dharmanol ™ is identical to that in all varieties of cannabis, but is sourced from other plants.”

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