ANDROGENS INDUCE NUMEROUS BENEFICIAL NEURAL EFFECTS
The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. In brain, low testosterone is an established factor for the development of Alzheimer’s disease (AD). Androgens induce numerous beneficial neural effects relevant to a protective role against AD, including reduction of the AD-related protein β-amyloid (Aβ) and promotion of synapse formation, neurogenesis, and specific aspects of cognition. An androgen action particularly important to neurodegenerative diseases is neuroprotection. Testosterone can increase neuron survival in several cell culture and animal models of injury.
Androgen-based hormone therapy may be an effective approach for the prevention of AD and related neurodegenerative disorders in aging men. However, the use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed “selective androgen receptor modulators” (SARMs) have been developed that lack significant androgen action in prostate but exert agonist effects in select androgen-responsive tissues.
NEUROPROTECTIVE EFFECTS OF RAD140
In a scientific study published in 2014, the neuroprotective effects of RAD140 in cultured rat neurons and male rat brain were investigated. Neuroprotection is an important neural action of endogenous androgens that is relevant to neural health and resilience to neurodegenerative diseases.
In cultured hippocampal neurons, RAD140 was as effective as testosterone in reducing cell death induced by apoptotic insults. Mechanistically, RAD140 neuroprotection was dependent upon MAPK signaling, as evidenced by elevation of ERK phosphorylation and inhibition of protection by the MAPK kinase inhibitor U0126. Importantly, RAD140 was also neuroprotective in vivo using the rat kainate lesion model.
In experiments with gonadectomized, adult male rats, RAD140 was shown to exhibit peripheral tissue-specific androgen action that largely spared prostate, neural efficacy as demonstrated by activation of androgenic gene regulation effects, and neuroprotection of hippocampal neurons against cell death caused by systemic administration of the excitotoxin kainate. These novel findings demonstrate initial preclinical efficacy of a SARM in neuroprotective actions relevant to Alzheimer’s disease and related neurodegenerative diseases.
RAD140 HAS THE POTENTIAL TO FIGHT BREAST CANCER
Breast cancer is the second leading cause of cancer-related death in women. Scientific study published in December 2017 in the journal of the American Association for Cancer Research demonstrated for the first time that RAD140 is an Androgen receptor (AR) agonist in breast cancer cells and suppresses the growth and proliferation of multiple AR/ER+ breast cancer cell line and xenograft models.
Steroidal androgens suppress Androgen receptor (AR) and Estrogen receptor (ER) positive (AR/ER+) breast cancer cells and were used to treat breast cancer, eliciting favorable response. The performed study evaluated the activity and efficacy of the oral Selective androgen receptor modulator RAD140 in in vivo and in vitro models of AR/ER+ breast cancer. A series of in vitro assays were used to determine the affinity of RAD140 to 4 nuclear receptors and evaluate its tissue-selective AR activity. The efficacy and pharmacodynamics of RAD140 as monotherapy or in combination with palbociclib were evaluated in AR/ER+ breast cancer xenograft models.
RAD140 bound AR with high affinity and specificity and activated AR in breast cancer but not prostate cancer cells. Oral administration of RAD140 substantially inhibited the growth of AR/ER+ breast cancer patient-derived xenografts. Patient derived xenografts (PDX) are models of cancer where the tissue or cells from a patient’s tumor are implanted into an immunodeficient or humanized mouse. PDX models are used to create an environment that allows for the natural growth of cancer, its monitoring, and corresponding treatment evaluations for the original patient.
The AR pathway was found to be activated in RAD140-treated breast cancer cells and xenografts, while genes within the ER pathway, including ESR1, were suppressed. In addition, RAD140 treatment was found to decrease the expression of DNA replication–related genes in breast cancer cells, consistent with previous report that these genes were suppressed in androgen-treated prostate cancer cells. Combined administration of RAD140 with the CDK4/6 inhibitor palbociclib was more efficacious compared with either of the agents used alone.
These findings suggest a distinct mechanism of action of RAD140, which includes the AR-mediated suppression of ESR1 in inhibiting AR/ER+ breast cancer growth. The potent antitumor activity and tissue-selective AR activity, along with overall tolerability in animal models and oral availability together lend support to further clinical investigation of RAD140 in AR/ER+ breast cancer patients..
RAD140 (TESTOLONE) AND BODYBUILDING
Similar to anabolic steroids, RAD140 effectively stimulates the growth of muscle mass. However, its safety profile is significantly better compared to steroids. RAD140 has significantly fewer dangerous and undesirable side effects, and the potential health risks are many times lower than those that can be caused by anabolic steroid use. Therefore, RAD140 is also used (abused) by bodybuilders, athletes and people who are trying to achieve a muscular figure, want to achieve similar results as when using steroids, but also want eliminate / minimize possible unwanted side effects. We emphasize that RAD140 is not an approved nutritional supplement or stimulant for athletes: RAD140 is an experimental substance that is still under investigation, its long-term effects are not yet fully known and further research is needed. Keep in mind that RAD140, like all our other products, is sold solely for scientific and research clinical use.