Biotechnological Approaches for Production of Anti-Cancerous Compounds Resveratrol, Podophyllotoxin and Zerumbone

Abstract

Secondary metabolites from numerous plant sources have been developed as anti-cancer reagents and compounds such as resveratrol, podophyllotoxin and zerumbone are of particular importance in this regard. Since their de novo chemical synthesis is both arduous and commercially expensive, there has been an impetus to develop viable, biotechnological methods of production. Accordingly, this review focuses on recent developments in the field, highlighting the use of micropropagation, cell suspension cultures, callus cultures, hairy root cultures, recombinant microbes and genetically modified higher plants. Optimization of media and culture conditions, precursor feeding, immobilization and the use of chemical or physical elicitation in various protocols has lead to increase in resveratrol and podophyllotoxin production. Heterologous gene transformation of higher plants with stilbene synthase derived from Arachis hypogaea or Vitis vinifera lead to resveratrol production with the concomitant increase in resistance to plant pathogens. Interestingly, genetic transformation of Podophyllum hexandrum and Linum flavum with Agrobacterium rhizogenes resulted in Ri-T-DNA gene(s)-mediated enhancement of podophyllotoxin production. Zerumbone yields from tissue cultured plantlets or from suspension cultures are generally low and these methods require further optimization. In microbes lacking the native resveratrol or zerumbone biosynthesis pathway, metabolic engineering required not only the introduction of several genes of the pathway, but also precursor feeding and optimization of gene expression to increase their production. Data pertaining to safety and toxicity testing are needed prior to use of these sources of anti-cancer compounds in therapy.

The aldehyde group of gossypol induces mitochondrial apoptosis via ROS-SIRT1-p53-PUMA pathway in male germline stem cell

“…Data showed that Res could relieve the gossypol-induced apoptosis of spermatogenic cells in a low concentration such as 10 μM, which has potential applications in the mitigation of feed toxicity and chemotherapy side-effect. With the development of biotechnological approaches for Res production [ 40 ], compared with the traditional methods to remove the gossypol from cottonseed, it is economic and good effect for large-scale application in Res added directly.…”

Propagation of Podophyllum hexandrum Royale to Enhance Production of Podophyllotoxin

“…The roots were incubated in flasks containing 25-ml MS media in a rotary shaker running at 100 rpm in the dark. [35]. L. flavum hairy roots were cocultured with P. hexandrum cell suspension cultures in a dual 500-ml shaker flask with the bottom side openings linked by a 4-5 cm length of 3 mm silicone tubing.…”

“…Biotransformation approach of podophyllotoxin production has helped to develop the derivatives of this resin, which have enhanced the anticancer properties coupled with the antimitotic activity of podophyllotoxin. So, Rajesh et al initiated the Agrobacterium-mediated biotransformation of P. hexandrum for increased production of podophyllotoxin [35]. Mature seeds of the plant were collected from its natural habitat, washed with running tap water, and then rinsed with 0.1% (v/v) Teepol solution.…”

Morphogenesis, Genetic Stability, and Secondary Metabolite Production in Untransformed and Transformed Cultures

“…Currently, cell culture brought to industrial scale is one of the major commercial sources of taxol. Resveratrol is a naturally occurring polyhydroxystilbene with several important biological and pharmacological properties generally produced in low amounts in a few plant species such as Vitis vinifera, Arachis hypogaea, and mulberries through phenylpropanoid pathway [125]. Resveratrol extracted from conventional cell suspension cultures and callus cultures of A. hypogaea or V. vinifera are in relatively low amounts [26,125].…”

“…Resveratrol is a naturally occurring polyhydroxystilbene with several important biological and pharmacological properties generally produced in low amounts in a few plant species such as Vitis vinifera, Arachis hypogaea, and mulberries through phenylpropanoid pathway [125]. Resveratrol extracted from conventional cell suspension cultures and callus cultures of A. hypogaea or V. vinifera are in relatively low amounts [26,125]. Several novel biotechnological approaches such as optimization of culture medium and conditions, utilization of different elicitor molecules, establishment of HRC, and genetic manipulation of the resveratrol biosynthesis pathway have been developed to optimize resveratrol production [26,[123][124][125][256][257][258].…”