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Natural Anticancer drugs and Recent Developments in it


Terrestrial Sources
Plants have a long history of use in the treatment of cancer, though many of the claims for the efficacy of such treatment should be viewed with some skepticism because cancer, as a specific disease entity, is likely to be poorly defined in terms of folklore and traditional medicine.9,10 Some plant anticancer drugs in clinical use or development are listed in Tables  Micro-organisms are a prolific source of structurally diverse bioactive metabolites and have yielded some of the most important products of the pharmaceutical industry. These include antibacterial agents, such as the penicillins (from Penicillium species), cephalosporins (from Cephalosporium acremonium), aminoglycosides, tetracyclines, and other polyketides of many structural types (from the Actinomycetales); immunosuppressive agents, such as the cyclosporins (from Trichoderma and Tolypocladium species) and rapamycin (from Streptomyces species); cholesterollowering agents, such as mevastatin (compactin; from Penicillium species) and lovastatin (from Aspergillus species); and anthelmintics and antiparasitic drugs, such as the ivermectins (from Streptomyces species). Antitumor antibiotics are among the most important of the cancer chemotherapeutic agents. Some clinically useful drugs and agents in development are listed in Table 1.

Table 1. Representative Plant-Derived Drugs in Clinical Use or Development

Drug Class

Example

Source Plant

Collection/Source Region

Development
Stage

Vinca alkaloids*

Vinblastine, vincristine,

Vinorelbine

Catharanthus

 roseus

The Philippines,

Jamaica, Madagascar

Clinical use

Lignans*

Etoposide, teniposide

Podophyllum

species

Eastern United States,

 Himalayas

Clinical use

Taxanes*

Paclitaxel, docetaxel

Taxus species

Northwest United

States, Europe

Clinical use


Camptothecins*

Topotecan, irinotecan HCl

Camptotheca

acuminata

China

Clinical use

Cephalotaxanes

Homoharringtonine

Cephalotaxus

harringtonia

China

Clinical trials

Flavones

Flavopiridol (synthetic based

 on rohutikine)

Dysoxylum

binectariferum

India

Clinical trials

Stilbenes*

Combretastatin prodrug

(AVE8062A)

Combretum

 caffrum

South Africa

Clinical Trials

Table 2. Representative Microbial-Derived Anticancer Drugs in Clinical Use and Development

Drug Class Example Source Organism Development Stage
Anthracyclines* Daunomycin, doxorubicin Streptomyces species Clinical use
Glycopeptides Bleomycins A2 and B2 Streptomyces verticillus Clinical use
Peptolides Dactinomycin Streptomyces species Clinical use
Mitosanes Mitomycin Streptomyces species Clinical use
Rapamycins* RAD001 Streptomyces species Phase I
Staurosporins* UCN-01, CEP-751 Streptomyces species Phase I, II
Epothilones* EPO906 (epothilone B) Sorangium cellulosum Phase I, II
Cryptophycins Cryptophycin-52 (synthetic) Nostoc species              cyanobac  (cyanobacteria) Phase I

Marine Sources
The world’s oceans, covering more than 70% of the earth’s surface, represent an enormous resource for the discovery of potential chemotherapeutic agents. Of the 33 animal phyla listed by Margulis and Schwartz,12 32 are represented in aquatic environments, with 15 being exclusively marine and 17 being both marine and nonmarine (with five of these having _ 95% of their species only in marine environments), and only one, Onychophora, is exclusively nonmarine. Before the development of reliable scuba-diving techniques some 40 years ago, the collection of marine organisms was limited to those obtainable by skin diving. Subsequently, depths from approximately 10 feet to 120 feet became routinely attainable, and the marine environment has been increasingly explored as a source of novel bioactive agents. The marine environment has proved to be a prolific source of structurally novel bioactive agents, and several have advanced to clinical development as potential anticancer agents.10,11,15 The interest in nature as a source of potential chemotherapeutic agents continues. An analysis of the number and sources of anticancer and anti-infective agents, reported mainly in the annual reports of Medicinal Chemistry from 1984 to 199 covering the years 1983 to 1994, indicates that more than 60% of the approved drugs developed in these disease areas can trace their lineage back to a natural product structure.

Table 3. Current Marine Organism–Derived Anticancer Drugs in Development

Drug Name

Source Organism (type)

Collection Region

Development Stage

Aplidine

Aplidium albicans (tunicate)

Mediterranean sea

Phase I, II

Bengamide analog

Jaspis species (sponge)

Fiji

Phase I

Bryostatin 1

Bugula neritina (bryozoan)

Gulf of California

Phase II

Discodermolide

Discodermia dissoluta (sponge)

Caribbean sea

Phase I

Dolastatin 10

Dolabella auricularia (mollusk)

Indian Ocean

Phase I

Ecteinascidin 743

Ecteinascidia turbinata ( tunicate)

Caribbean Sea

Phase II, III

Squalamine

Squalus acanthias (dogfish shark)

Atlantic Ocean

Phase II

Kahalahide F

Elysia rubefescens (mollusk)

Hawaii

Phase I, II

Halichondrin B analog

Lissodendoryx species (sponge)

New Zealand

Phase I

Hemiasterlin analog*

Cymbastella species (sponge)

Papua New Guinea

Phase I

Isogranulatimide*

Didemnum granulatum (tunicate)

Brazil

Phase I

*Several semisynthetic analogs are earlier in development.

Recently invented natural drug therapies as anticancer treatment

BRITISH FLOWERS ARE THE THE SOURCE OF NEW ANTICANCER DRUG:

Researchers are poised to start clinical trials with a new "smart bomb" treatment, derived from the flower, targeted specifically at tumours. The treatment, called colchicine, was able to slow the growth of and even completely "kill" a range of different cancers, in experiments with mice.  The research was highlighted at the British Science Festival in Bradford. The team behind it, from the Institute for Cancer Therapeutics (ICT) at the University of Bradford, has published the work in the journal Cancer Research. The native British Autumn crocus, otherwise known as "meadow saffron" or "naked lady", is recorded in early herbal guides as a treatment for inflammation. This is because it contains the potent chemical colchicine, which is known to have medicinal properties, including anti-cancer effects. But colchicine is toxic to other tissues in the body, as well as cancer, so until now its use has been limited. The researchers at ICT have now altered the colchicine molecule so it is inactive in the body until it reaches the tumour.  Once there, the chemical becomes active and breaks up the blood vessels supplying the tumour, effectively starving it.  This effect is made possible because of enzymes that all tumours produce, whose usual function is to break down the normal cells nearby, allowing the tumour to spread. The modified colchicine molecule has a protein attached to it that makes it harmless. But the tumour enzyme specifically targets the protein and removes it. The colchicine is then activated, and the process of breaking down blood vessels and starving the cancerous cells begins.  Because the enzyme necessary to activate the toxic colchicine is produced only by solid tumours, it may be possible to treat cancers effectively with virtually no side effects to the rest of the body. The researchers report having tested the effectiveness of this therapy at treating tumours in mice. The treatment has reportedly been tested on five different types of cancer in the laboratory, including breast, colon, lung, sarcoma and prostate. These tests have reportedly been successful to varying degrees, with no adverse effects reported. The researchers report a greater than “70% cure rate after a single dose”. Some of the work described at the festival may have been described in a related paper in the journal Cancer Research in 2010, entitled “Development of a novel tumour-targeted vascular disrupting agent activated by MT-MMPs”. This study focused on the effects of a derivative of colchicine, which the researchers called ICT2588, on one type of tumour in mice (fibrosarcoma).

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