Bruceantin is a compound isolated from Brucea antidysenteriea, a plant used in Ethiopia as an anticancer treatment. The primary action of Bruceantin appears to be an inhibition of protein synthesis which takes place at the ribosomal level. Bruceantin induced marked decreases of c-myc mRNA and protein expression in all cell lines. Bruceantin-induced c-myc downregulation might trigger cell death mechanisms preferentially in those cell lines with wild-type p53 protein expression. Bruceantin was evaluated in three separate phase I clinical trials in patients with various types of solid tumors. Hypotension, nausea, and vomiting were common side effects at higher doses, but hematologic toxicity was moderate to insignificant and manifested mainly as thrombocytopenia. Bruceantin was then tested in two separate phase II trials including adult patients with metastatic breast cancer and malignant melanoma. No objective tumor regressions were observed, and clinical trials were terminated.

Cucurbitacin B (CuB), an oxygenated tetracyclic triterpenoid compound extracted from Cucurbitaceae plant species, is a long-term anticancer agent by disruption of microtubule polymerization. Cucurbitacin B is a naturally occurring compound that is found abundantly in cucumbers and other vegetables, and it is known to exert anti-cancer activities (primarily via apoptosis-induction) in several human cancers. Cucurbitacin B also protects against cardiac hypertrophy through increasing the autophagy level in cardiomyocytes, which is associated with the inhibition of Akt/mTOR/FoxO3a signal axis. ACLY over-expression abrogated CuB's apoptotic effects in prostate cancer cells, confirming ACLY as a direct target of CuB. Thus, CuB harbors potent chemopreventive activity for prostate cancer, and we revealed a novel anti-tumor mechanism of CuB via inhibition of ACLY signaling in human cancer. It has being suggested that cucurbitacin B exerts an anticancer effect by inhibiting telomerase via down regulating both the hTERT and c-Myc expression in breast cancer cells.

3,3′-diindolylmethane or diindolylmethane (DIM), a natural product from cruciferous vegetables, which possesses chemopreventive activity in all stages of breast cancer carcinogenesis and is under investigation for the different form of cancer. DIM selectively induced proteasome-mediated degradation of the class I histone deacetylases (HDAC1, HDAC2, HDAC3, and HDAC8) without affecting the class II HDAC proteins (HDAC4, 5, 6, 7, and 10). Histone deacetylases are components of high molecular weight multisubunit complexes of co-repressor proteins that are recruited by transcription factors to the promoters to regulate gene expression. In addition, was identified another mechanism of action: DIM suppressed cancer cells proliferation and miR-30e down-regulated during this effect. miR-30e targeted the 3'-UTR of ATG5 to inhibit its translation. Thus DIM may through the miR-30e-ATG5 modulating autophagy inhibit the proliferation of gastric cancer cells. DIM is also sold as absorption-enhanced formulation under the brand name Patented BioResponse DIM®. BioResponse DIM supports a more favorable metabolism of estrogen and supports the production of 2 hydroxyestrone and 2-methoxyestrone, key metabolites in men and women. DIM is used to treat recurrent respiratory papillomatosis and it has been studied for patients with cervical intraepithelial neoplasia.

Naringenin is one of the most abundant flavonoids in natural citrus fruits and has been studied as an antioxidant and anti-inflammatory agent. Besides, it has been investigated for its ability to inhibit the growth of breast, colon, gastric and prostate cancer cells. Experiments on rodents have revealed, that naringenin is a component of Drynaria Rhizome and can enhance memory function and ameliorate Alzheimer's disease pathologies. Using the experimental autoimmune encephalomyelitis, a rodent model of human multiple sclerosis was determined that naringenin may have a potential to ameliorate autoimmune disease by favorably modulating autoimmune response. The precise mechanism of action of naringenin compound is not clear, but it is known, that it is a partial agonist of estrogen receptor that can act as a competitive antagonist in the presence of a potent (or full) agonist. In addition, it binds to collapsin response mediator protein 2 protein (CRMP2) and reduces the Aβ-induced phosphorylation of CRMP2, resulting in axonal growth facilitation.

Clodronate (also known as clodronic acid) is a drug used to treat a high level of calcium in the blood caused by changes in the body that happen with cancer. Clodronate is approved in some countries and is sold under trade trade name bonefos for oral use. Bonefos is indicated in the management of osteolytic lesions, hypercalcemia and bone pain associated with skeletal metastases in patients with carcinoma of the breast or multiple myeloma. Bonefos is also indicated for the maintenance of clinically acceptable serum calcium levels in patients with hypercalcemia of malignancy initially treated with an intravenous bisphosphonate. Bonefos forms complexes with divalent metal ions, and therefore simultaneous administration with food, antacids and mineral supplements may impair absorption. It was suggested, that the mechanism of action of clodronate was involved osteoclast apoptosis.

N-hexanoylsphingosine is biologically active, cell permeable but nonphysiologic ceramide analog. Liposomal N-hexanoylsphingosine activates protein phosphatase 1 to inhibit melanoma cells. N-hexanoylsphingosine activates a cytosolic serine/threonine protein phosphatase in a dose-dependent manner. It induces cytochrome c (Cyt c) release from isolated rat liver mitochondria. It sensitizes vincristine-induced anticancer activity in vivo and in vitro, involving activating AMPK-p53 signaling.

Methylinositol is a natural product in the family of inositols. It is found in many foods as well as pine tree bark. Methylinositol is found naturally in many foods and is commercially available as an approved food supplement. Methylinositol can mediate insulin action to improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus, especially in patients with insulin resistance. It plays a positive role in regulating insulin-mediated glucose uptake in the liver through translocation and activation of the PI3K/Akt signaling pathway. The compound also modulates gamma-secretase to reduce A-betta production while sparing cleavage of the gamma-secretase substrate Notch. Methylinositol improves cognitive function and memory deficits in preclinical models of Alzheimer's disease (AD) neuropathology. Methylinositol was will tolerated in the population of AD subjects of varying age and severity. No serious adverse effects were detected in clinical trials. Many plant-derived compounds have excellent therapeutic potential against various human ailments. It was shown, that methylinositol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB.

Stevioside, an abundant component of Stevia rebaudiana leaf, has become well-known for its intense sweetness (250-300 times sweeter than sucrose) and is used as a non-caloric sweetener in several countries. Steviol and isosteviol (metabolic components of stevioside) may offer therapeutic benefits, as they have anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions. In the presence of 16.7 mM glucose both stevioside and steviol enhance insulin secretion from incubated islets in a dose-dependent manner (1 nM to 1 mM). Even though both stevioside and steviol possess an insulinotropic/anti-hyperglycemic effect, steviol is more potent than stevioside. Steviol is an inhibitor of hOAT1 and hOAT3 organic anion transporters. Human organic anion transporter hOAT1 belongs to a superfamily of organic anion transporters, which play critical roles in the body disposition of clinically important drugs including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories. Highly purified steviol glycosides have repeatedly received Generally Recognized As Safe (GRAS) status from the US Food and Drug Administration in the past (FDA).

Tetraxetan (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (also known as DOTA) is used as a complexing agent. Its complexes have medical applications as contrast agents and cancer treatments. DOTA can be conjugated to monoclonal antibodies by attachment of one of the four-carboxyl groups as an amide. The modified antibody accumulates in the tumour cells, concentrating the effects of the radioactivity of 90Y. DOTA can also be linked to molecules that have an affinity for various structures. The resulting compounds are used with a number of radioisotopes in cancer therapy and diagnosis. Clivatuzumab tetraxetan is a humanized monoclonal antibody targeting a mucin antigen expressed in most pancreatic cancers, but not pancreatitis, normal pancreas or most other normal tissues. Preclinical studies in mice with human pancreatic cancer xenografts given the murine version of 90Y-clivatuzumab tetraxetan demonstrated favourable tumour responses, which could be further improved when given in combination with gemcitabine. (64)Cu-DOTA-trastuzumab PET (positron emission tomography) could be a potential noninvasive procedure for serial identification of metastatic brain lesions in patients with HER2-positive breast cancer. 90Y-DOTA-biotin may have the application of pre-targeted radioimmunotherapy for the treatment of advanced colorectal cancer in humans.

Tetrahydrodiferuloylmethane (aka Tetrahydrocurcumin) is a bioactive metabolite of curcumin. It has been shown to have anti-inflammatory, anti-oxidant, anti-cancer, and neuroprotective effects in several in vitro and in vivo models. However, there have been no advances in human trials for these conditions. It should be noted that tetrahydrocurcumin is used in non-medicinal skin care formulations intended for skin whitening, skin soothing, and anti-oxidant effects.