Camptotheca acuminata

Camptothecin was discovered as an active anticancer drug isolated from the bark of Camptotheca acuminata. The anticancer activity of camptothecin was discovered in the 1960s by the National Cancer Institute (NCI) as part of a systematic effort to screen for novel anticancer agents derived from natural products. Monroe Wall and Mansuhk Wani identified the chemical structure of camptothecin. They also identified the chemical structure of taxol, again under the auspices of the NCI. Susan Hoiwitz was contracted by the NCI to elucidate the anticancer mechanisms of camptothecin. She found in the early 1970s that camptothecin induced DNA breaks and attested DNA and RNA synthesis. However, it is approximately 12 years later, only after DNA topo-isomerase I (Topi) had been identified in human cells, that Leroy Liu and his coworkers found that Topi was the cellular target of camptothecin [reviewed in [1]. 

First generation of topi inhibitors were developed as drugs from camptothecins, a family of compounds derived from wood and bark of the Chinese tree Camptotheca acuminata) [9, 10], Many of these are already in clinical use or clinical trials, including irinotecan, topotecan, exatecan, rubitecan, and lurtotecan. Irinotecan (CPT-11) is bioactivated in liver by carboxylesterase to the active metabolite SN-38, 1000-fold more active [11]. Irinotecan received in 1998 FDA approval for treatment of metastatic colorectal cancer after failure of treatment with 5FU [12],... 

Wall and Wani collaborated in their research on Taxux brevifolia and Camptotheca acuminata for 38 years. They have received some of the most prestigious awards given in their field of science, most notably the 2000 Charles F. Kettering Prize for outstanding research on the diagnosis or treatment of cancer. 

Representatives of another important class of plant-derived semisynthetic compounds are the camptothecin (27) derivatives, irinotecan (28) and topotecan (29). Camptothecin (27) was originally discovered as an antileukemic agent in a mouse model when isolated from Camptotheca acuminata Decne. Compounds (28) and (29) are both employed in cancer chemotherapy. These substances are important mechanistically because of their activity against the enzyme, topoisomerase I. These compounds were designed to address efficacy and toxicity concerns with the parent compound, camptothecin, and its sodium salt. ... 

Zhao X et ai, Effects of arbuscular mycorrhiza on camptothecin content in Camptotheca acuminata seecUings, Shengtai Xuebao 26 1057—1062, 2006. 

Camptothecin is a plant alkaloid obtained from the Camptotheca acuminata tree. It was first evaluated clinically, as a sodium salt, in the 1960s and 1970s, but was abandoned because of severe and unpredictable hemorrhagic cystitis (3,4). Irinotecan (CPT-11) and Rubetecan are semisynthetic, water-soluble derivatives of camptothecin possessing... 

Indole alkaloids Tryptophane decarboxylase Catharanthus roseus Camptotheca acuminata... 

Figure 10.6 The antitumoral camptothecin (CPT), a lipophilic drug extracted from the Chinese tree Camptotheca acuminata, can be incorporated into the liposome bilayer due to its lipophilic character. The CPT-containing liposomes are studied as antitumor drug formulations. (Modified from Stano et al 2004.)...

Camptotheca acuminata Decne. Xi Shu (Happy tree) (fruit) Camptothecine, venoterpine, hydroxyleamptothecin, methoxyl-camptothecin, irinotecan, 10-hydroxycamptothecin 33-457-458469 This herb is toxic. Treat breast cancer, carcinoma of the stomach, rectum, colon and bladder, chronic leukemia. 

Hepatica asiatica Nakai Camptotheca acuminata Decne. 

A. lagocephala, A. lavandulaefolia, A. scoparia, A. selengensis, A. sieversiana, A. vulgarts, Chrysanthemum boreale, C. indicum, C. lavandulaefolium, C. procumbens, C. tripartium Elettaria cardamomum Camptotheca acuminata... 

Daphne fortunei, D. genkwa, Wikestroemia indica Camptotheca acuminata Angelica decursiva... 

Camptothecin (1) was first extracted from the hcartwood of the tree species Camptotheca Acuminata Nxssaceac by Wall1 in 1966. Its structure was verified by X-ray analysis2 of its C-20 iodoaceiale ester. 

Isolated in low yield (0.005%) from the bark and stem wood of Camptotheca acuminata Decaisne (family Nyssaceae) native to China [248-250], and sub-... 

Camptothecin (Figure 6.93) from Camptotheca acuminata (Nyssaceae) is a further example of a quinoline-containing structure that is actually derived by modification of an indole system. The main rearrangement process is that the original (>-carboline 6-5-6 ring system becomes a 6-6-5 pyrroloquinoline by ring expansion of the indole... 

Another important anticancer natural product is camptothecin, an alkaloid derived from the Chinese tree Camptotheca acuminata Descne. A semisynthetic water-soluble derivative of camptothecin known as ironotecan (Topotecin , Campto ) was introduced in Japan in 1994 for the treatment of lung, ovarian, and cervical cancers. Unlike Taxol, camptothecin acts by inhibition of the enzyme topoisomerase I. 

Camellia sinensis (Tea, green tea, black tea) Camptotheca acuminata (Xi shu, tree of joy, happy tree, cancer tree)... 

It has been used to treat leukemia. Other anticancer drugs have been modified from Camptotheca acuminata. Topotecan is used to treat ovarian and small-lung cancers. Irinotecan is used to treat metastatic colorectal cancer. 

The camptothecins are natural products that are derived from the Camptotheca acuminata tree, and they inhibit the activity of topoisomerase I, the key enzyme responsible for cutting and religating single DNA strands. Inhibition of the enzyme results in DNA damage. Topotecan is indicated in the treatment of patients with advanced ovarian cancer who have failed platinum-based chemotherapy and is also approved as second-line therapy of small cell lung cancer. The main route of elimination is renal excretion, and for this reason caution must be exercised in patients with abnormal renal function, with dosage reduction being required. 

Irinotecan (1) is a derivative of the pentacyclic quinoline alkaloid camptothecin (2) the latter was first isolated from the heartwood of the tree species Camptotheca acuminata (Nyssacea) by Wall et al. in 1966.1 Two years later A. T. McPhail and G. A. Sim determined the structure of 2 by X-ray analysis.2... 

LOPEZ-MEYER, M., NESSLER, C.L., Tryptophan decarboxylase is encoded by two autonomously regulated genes in Camptotheca acuminata which are... 

Induction of strand breakage may result from inhibition of topoisomerase. The epi-podophyllotoxins etoposide and tenoposide interact with topoisomerase II, which functions to split, transpose, and reseal DNA strands (p.276) these agents cause strand breakage by inhibiting resealing. The te-cans topotecan and irinotecan are derivatives of camptothecin from the fruits of a Chinese tree (Camptotheca acuminata). They inhibit topoisomerase I, which induces breaks in single-strand DNA. 

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