Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

Abstract

Novel and alternative options are being adopted to combat the initiation and progression of human cancers. One of the approaches is the use of molecules isolated from traditional medicinal herbs, edible dietary plants and seeds that play a pivotal role in the prevention/treatment of cancer, either alone or in combination with existing chemotherapeutic agents. Compounds that modulate these oncogenic processes are potential candidates for cancer therapy and may eventually make it to clinical applications. Diosgenin is a naturally occurring steroidal sapogenin and is one of the major bioactive compounds found in dietary fenugreek (Trigonella foenum-graecum) seeds. In addition to being a lactation aid, diosgenin has been shown to be hypocholesterolemic, gastro- and hepato-protective, anti-oxidant, anti-inflammatory, anti-diabetic, and anti-cancer. Diosgenin has a unique structural similarity to estrogen. Several preclinical studies have reported on the pro-apoptotic and anti-cancer properties of diosgenin against a variety of cancers, both in in vitro and in vivo. Diosgenin has also been reported to reverse multi-drug resistance in cancer cells and sensitize cancer cells to standard chemotherapy. Remarkably, diosgenin has also been reported to be used by pharmaceutical companies to synthesize steroidal drugs. Several novel diosgenin analogs and nano-formulations have been synthesized with improved anti-cancer efficacy and pharmacokinetic profile. In this review we discuss in detail the multifaceted anti-cancer properties of diosgenin that have found application in pharmaceutical, functional food, and cosmetic industries; and the various intracellular molecular targets modulated by diosgenin that abrogate the oncogenic process.

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

“…Diosgenin (DG) is a naturally occurring steroidal sapogenin isolated from Agavaceae, Dioscoreaceae, Liliaceae, Solanaceae, Scrophulariaceae, Amaryllidaceae, Leguminosae, and Rhamnaceae [12][13][14][15][16][17]. It has been extensively studied for the management and treatment of different types of cancer [18], osteoporosis [19], cardiovascular diseases [20], atherosclerosis [21], diabetes mellitus [22], and skin diseases [23]. DG is being increasingly investigated in the treatment of neurological diseases [24].…”

“…Despite its pharmacological activities in the treatment of various diseases, the clinical application of DG is severely hindered by its low aqueous solubility, poor bioavailability and pharmacokinetics, and rapid biotransformation under physiological conditions [28]. Several recent reviews have provided a comprehensive account of its pharmacological effects in cancer [18], diabetes mellitus, metabolic syndrome [29], and others [24,30]. In this review, we will discuss recent progress of DG as a therapeutic agent against various neurological diseases along with its mechanisms of action in CNS.…”

Acid hydrolysis of saponin‐rich extracts of quinoa, lentil, fenugreek and soybean to yield sapogenin‐rich extracts and other bioactive compounds

“…Concerning steroid saponins, fenugreek extracts have been shown to improve the serum lipid, bile acid efflux, anti‐peroxide activities, and lipid area of liver tissue in rats, ameliorating dyslipidaemia by accelerating cholesterol metabolism, inhibiting cholesterol synthesis, and facilitating reverse cholesterol transport . Fenugreek saponins are also known for their pro‐apoptotic and anticancer properties …”

“…12 Fenugreek saponins are also known for their pro-apoptotic and anticancer properties. 13 Unfortunately, saponins are poorly absorbed during digestion and exhibit low bioavailability due to various limiting factors such as low membrane permeability, chemical transformations, or colonic fermentation. 14 On the other hand, most sapogenins have demonstrated superior bioavailability, and some bioactivities of sapogenins are even more pronounced than those of their former saponins, due to more favorable chemical properties caused by the lack of the sugar chain.…”

Alternative Treatments for Cancer Prevention and Cure [Part 1]

“…Effectively inhibited SW480 CRC cell proliferation, down-regulation of Shoc2 expression also significantly inhibited proliferation, colony formation, and migration functions of tumor cells [498]. Inhibited the invasion and migration abilities of RKO cells and decreased the expression of MMP-7, MMP-9, and suppressed the growth of colorectal cancer cells by inhibiting VEGFR2 [507,508], decreased viability of CoCa cells and induced apoptosis in a time and dosedependent manner, down regulated Bcl-2 family expression [509]. Mitochondrial dysfunction and ROS accumulation in colon cancer cells also reported [510].…”