Cancer remains a frightening and largely incurable disease. The toxic side effects of chemotherapy and radiation make the cure often seem as bad as the ailment, and there is also the threat of recurrence and tumour spread.
Cancer treatment still follows a practically medieval method of cut, burn or poison. If the growth can’t be cut out through surgery, it may be burnt away with radiation or poisoned by chemotherapy. As a result, cancer therapy remains a daunting diagnosis for patients and treatment options seem limited for a disease which causes one in six deaths globally.
The failure to innovate in cancer treatment may lie in the very poor success rate of clinical trials. Approximately 95%-98% of new anti-cancer drugs actually fail phase III clinical trials, the phase in which new treatments are compared with existing therapy options. This is a staggering statistic.
Cancer is the second leading cause of death worldwide. Although great advancements have been made in the treatment and control of cancer progression, significant deficiencies and room for improvement remain. A number of undesired side effects sometimes occur during chemotherapy. Natural therapies, such as the use of plant-derived products in cancer treatment, may reduce adverse side effects. Currently, a few plant products are being used to treat cancer. However, a myriad of many plant products exist that have shown very promising anti-cancer properties in vitro, but have yet to be evaluated in humans. Further study is required to determine the efficacy of these plant products in treating cancers in humans. This review will focus on the various plant-derived chemical compounds that have, in recent years, shown promise as anticancer agents and will outline their potential mechanism of action.
Chemotherapy is routinely used for cancer treatment. Since cancer cells lose many of the regulatory functions present in normal cells, they continue to divide when normal cells do not. This feature makes cancer cells susceptible to chemotherapeutic drugs. Approximately five decades of systemic drug discovery and development have resulted in the establishment of a large collection of useful chemotherapeutic agents. However, chemotherapeutic treatments are not devoid of their own intrinsic problems.
Various kinds of toxicities may occur as a result of chemotherapeutic treatments. For example, 5-fluorouracil, a common chemotherapeutic agent, is known to cause myelotoxicity , cardiotoxicity and has even been shown to act as a vasospastic agent in rare but documented cases . Another widely used chemodrug, doxorubicin causes cardiac toxicity , renal toxicity , and myelotoxicity . Similarly, bleomycin a well known chemotherapeutic agent, is known for its pulmonary toxicity . In addition, bleomycin shows cutaneous toxicity . Cyclophosphamide, a drug to treat many malignant conditions, has been shown to have bladder toxicity in the form of hemorrhagic cystitis, immunosuppression, alopecia and at high doses cardiotoxicity .
The toxicity of chemotherapeutic drugs sometimes creates a significant problem in the treatment of cancer using allopathy or established medicine. Various therapies have been propounded for the treatment of cancer, many of which use plant-derived products. There are four classes of plant-derived anticancer agents in the market today, the vinca alkaloids (vinblastine, vincristine and vindesine), the epipodophyllotoxins (etoposide and teniposide), the taxanes (paclitaxel and docetaxel) and the camptothecin derivatives (camptotecin and irinotecan). Plants still have enormous potential to provide newer drugs and as such are a reservoir of natural chemicals that may provide chemoprotective potential against cancer. Recently, Taneja and Qazi, have suggested a number of compounds from medicinal plants with potential anti-cancer activities .
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MEDICINAL PLANTS AND CANCER
The anticancer properties of plants have been recognized for centuries. Isolation of podophyllotoxin and several other compounds (known as lignans) from the common mayapple (Podophyllum peltatum) ultimately led to the development of drugs used to treat testicular and small cell lung cancer . The National Cancer Institute (NCI) has screened approximately 35,000 plant species for potential anticancer activities. Among them, about 3,000 plant species have demonstrated reproducible anticancer activity.
Many studies have focused on the chemoprotective properties of plants such as anticarcinogenic properties of Abrus precatorius on Yoshida sarcoma in rats, fibrosarcoma in mice and ascites tumor cells . Similarly, Dhar et al. have examined the anticancer properties of Albizzia lebbeck on sarcoma in mice and Alstonia scholaries on benzo[a]pyrene-induced forestomach carcinoma in humans . Other plants that have shown anticarcinogenic properties include Anacardium occidentale in hepatoma, Asparagus racemosa in human epidermoid carcinoma, Boswellia serrata in human epidermal carcinoma of the nasopharynx, Erthyrina suberosa in sarcoma, Euphorbia hirta in Freund virus leukemia, Gynandropis pentaphylla in hepatoma, Nigella sativa in Lewis lung carcinoma, Peaderia foetida in human epidermoid carcinoma of the nasopharynx, Picrorrhiza kurroa in hepatic cancers, and Withania somnifera in various tumors .
Why Use Herbals?
There are many reasons cancer and mesothelioma patients may turn to natural alternative substances like herbals. Some people hold out hope for a real cure. However, it is important to remember many herbal supplements have not been studied or used in clinical trials. There are no herbals proven to actually cure cancer.
A better reason for using herbs and plants is that they can relieve symptoms of cancer and side effects of treatments, like chemotherapy. These herbal treatments can also improve overall health and well-being. From relieving nausea and reducing fatigue to helping to prevent the toxicity of chemotherapy drugs, these substances can help patients feel better life while battling cancer.
The anticancer characteristics of a number of plants are still being actively researched and some have shown promising results. Some plants and plant products that have shown promise as anticancer agents are discussed in detail in the following sections.
Turmeric is a spice well-known in Indian cuisine. This rich, gold-colored spice comes from the root of the turmeric plant. For cancer patients, the most important component of turmeric is curcumin. Curcumin has anti-inflammatory effects and may be able to slow the growth of tumors. Research has also shown curcumin to help with weight loss in cancer patients.
Boswellia comes from the Boswellia serrata tree which is native to India, the Middle East, and northern Africa. Resin from this tree has long been used as a medical supplement, especially in the ancient Indian healing system Ayurveda. Studies have found that some components of Boswellia have anti-inflammatory and anti-tumor properties. One study also found Boswellia reduces swelling in the brain after radiation treatment. This could prove important for patients with brain cancer.
Also known as wormwood, Artemesia annua is an herb used in traditional Chinese medicine. Artemisinin, the active ingredient in the herb, is known to have anti-malarial and anti-viral effects. Some research suggests artemisia may have anticancer effects in cell lining, which would be important for those dealing with lung cancer.
Another herb from traditional Chinese medicine is dong quai. Dong quai comes form the Angelica sinensis plant. The root has been used for hundreds of years in both food and medicine in China, Korea, and Japan. Modern research suggests dong quai may relieve some side effects of cancer treatment. It protects against the toxicity of some chemotherapy drugs, including cyclophosphamide and doxorubicin. Dong quai may also protect against pneumonitis, the inflammation in the lungs sometimes caused by radiation therapy for lung cancer or mesothelioma.
In China, green tea has been a popular beverage for thousands of years. Green tea comes from the Camellia sinensis plant, the source of non-herbal teas like black, oolong, white, and green teas. EGCG, an active compound in green tea has a proven preventative effect on cancer. It may also help to block the growth of tumors. Ongoing research is focusing on how EGCG may affect treatment of various types of cancer.
The ginseng root has long been used to combat fatigue and improve energy, especially in traditional Chinese medicine. Isolated active compounds in ginseng are proven to have anticancer properties. Studies with cancer patients have found that ginseng supplementation improve reported quality of life. There is also some evidence that ginseng may boost immune system function.
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Anticancer potential of curcumin: preclinical and clinical studies.
Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis.
Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies.
Annona atemoya Mabb.
Annona atemoya/muricata is a native of Caribbean, Central and South America. It is also commonly grown in South East Asia especially in eastern part of India. This plant is traditionally known as mamaphal in Hindi and sour-sop of America in English. The parts of the plant that are generally used for medicinal purposes are the root, bark, leaf and fruit.
The fruit of A. atemoya contains bullatacin (chemical structure shown below), an acetogenin known to have antitumor properties. Bullatacin induces chromatin margination and tumor cell condensation, followed by apoptosis . A. atemoya contains two annomuricins namely A and B, which have shown cytotoxicity in human solid tumor cell lines A-549 lung carcinoma, MCF-7 breast carcinoma, and HT-29 colon adenocarcinoma cell lines . A. atemoya contains several other acetogenins that have also been shown to selectively induce cell death in tumor cells in vitro . In particular, two annonaceous acetogenins were found to produce cell death in the human hepatoma cell line HepG2 and hepatoma 2.2.15 cells.
Mappia foetida Miers.
Mappia foetida/ Nothapodytes foetida is generally found in tropical countries . The medicinal properties of M. foetida have recently gained international attention. The active component of M. foetida tree wood is camptothecin (chemical structure shown below), a potent chemotherapy drug used to treat leukemia . Recent studies have indicated that an endophytic fungus which grows on this plant also produces the camptothecine . Camptothecines have broad spectrum of antitumor activities both in vitro and in vivo. For example, camptothecines have been shown to be effective inhibitors of nucleic acid synthesis in HeLa cells and L-120 cells . The anti-neoplastic activity of camptothecine has been attributed to its inhibitory action on the nuclear enzyme type-1 DNA topoisomerase .
This alkaloid as well as several semisynthetic or fully synthetic analogues, are in various stages of preclinical and clinical trials . Irinotecan (7-ethyl-10-[4-(Ipiperidino)-I-piperidinol] carbonyloxycamptothecine) is a new potent semi-synthetic derivative of camptothecine, which is active against ascites and solid mouse tumors and induces partial or complete remission of breast carcinoma in the xenograft model system . A series of Phase II clinical trials have been conducted to assess the anticancer activity of camptothecines and their analogues. The Phase II trials have revealed an extensive range of activities against lymphoma, leukemia, and solid epithelial tumors. Topotecan, another synthetic modification of 10-hydroxycamptothecine, has been shown to slow the growth of human colon cancer cells, rhabdomyosarcoma cells, and osteogenic sarcoma xenografts.
Herbals and botanicals as a complementary or alternative medicine is growing in popularity. More mesothelioma and cancer patients are turning to these natural substances to find relief from symptoms. Many also hope these substances will have an effect on tumors and cancer cells.
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