Anticancer activities

Lentinan and PSK are mushroom isolates used for anticancer activity in Japan and China. Irofulven and acylfulvene are semi-synthetic anticancer compounds derived from the mushroom isolate illudin S. Bristol-Myers Squibb produces paclitaxel using Penicillium raistrickii and plant cell fermentation (PCF). Endophytic fungi can synthesize the etoposide and teniposide precursor podophyllotoxin, as well as the topotecan and irinotecan precursor camptothecin. Clavariadelphus truncatus creates the farnesyltransferase inhibitor clavaric acid. Agaricus bisporus and Agaricus subrufescens create CLA. Inonotus obliquus creates the betulinic acid precursor betulin. Irofulven or 6-hydroxymethylacylfulvene (also known as HMAF of MGI-114) is an antitumor agent. It belongs to the family of drugs called alkylating agents. It inhibits the replication of DNA. Irofulven is an analogue of illudin S, a sesquiterpene toxin found in mushrooms of the genus Omphalotus. The compound was originally synthesized by Dr. Trevor McMorris (UCSD) and found to have anticancer properties by Dr. Michael J Kelner (UCSD). Acylfulvene is a cytotoxin that is related to illudin. Illudin itself can be extracted from the jack o'lantern mushroom (Omphalotus olearius). Acylfulvene is a compound that can be utilized towards the treatment of a wide assortment of cancers and tumors. It is thought that the acylfulvene compound cripples tumors by DNA alkylation (see DNA methylation), but the exact mechanism of action is not determined. At present, paclitaxel (Taxol) is the drug of choice to treat certain tumors a d cancers, but researchers claim[who?] that the efficacy of acylfulvene to fight various tumors is many times that of paclitaxel. The production and thus the use of acylfulvene is hampered by the fact that the extraction of illudin from mushrooms is difficult and also, at the present moment, acylfulvene is difficult to synthesize. Topotecan (trade name Hycamtin) is a chemotherapeutic agent that is a topoisomerase inhibitor. It is a water-soluble derivative of camptothecin. It is used in form of the hydrochloride to treat ovarian cancer and lung cancer, as well as other cancer types. After GlaxoSmithKline received final FDA approval for Hycamtin Capsules on October 15, 2007, topotecan is the first topoisomerase I inhibitor for oral use. Camptothecin (CPT) is a cytotoxic quinoline alkaloid which inhibits the DNA enzyme topoisomerase I (topo I). It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata (Camptotheca, Happy tree), a tree native to China used as a cancer treatment in Traditional Chinese Medicine. CPT showed remarkable anticancer activity in preliminary clinical trials but also low solubility and (high) adverse drug reaction. Because of these disadvantages synthetic and medicinal chemists have developed numerous syntheses of Camptothecin and various derivatives to increase the benefits of the chemical, with good results. Two CPT analogues have been approved and are used in cancer chemotherapy today, topotecan and irinotecan.