Conventional Chemotherapy: Problems and Scope for Combined Therapies with Certain Herbal Products and Dietary Supplements

Review Article

Austin J Mol & Cell Biol. 2014;1(1):10.

Conventional Chemotherapy: Problems and Scope for Combined Therapies with Certain Herbal Products and Dietary Supplements

Mondal J¹, Panigrahi AK² and Khuda-Bukhsh AR¹*

1Department of Zoology, University of Kalyani, India

2Department of Zoology, University of Kalyani, India

*Corresponding author: Khuda Bukhsh AR, Department of Zoology, Cytogenetics and Molecular Biology Laboratory, University of Kalyani, Kalyani-741235, India,

Received: June 27, 2014; Accepted: June 27, 2014; Published: August 28, 2014


Cancer, the dreadful disease, is one of the burning issues that need collective efforts to successfully combat and cure. Chemotherapy is one among many options like surgery, radiation therapy, targeted molecular therapy etc., which is widely used to successfully treat certain types of cancer, but its use is restricted for the adverse side-effects of most of the chemotherapeutic drugs. A comprehensive search by utilizing data from the Pubmed, Cochrane Library, Embase and ISI Web of Knowledge and some related books was made to gain insight into the modern trend of research to combat the obstacles that come in the way of waging a successful war against cancer. The toxic by-products of some chemotherapeutic drugs are deposited mainly in liver producing hepatotoxicity, leading to many side-effects like loss of appetite, nausea, vomiting, diarrhea, abdominal cramps and constipation, anemia, fatigue, hyperthermia, loss of hair etc. In this review, the benefits and problems of chemotherapy have been highlighted and the scope and obstacles of combined therapy with some biologically based complementary and alternative medicines (CAM) derived from certain herbal products and dietary supplements, plant extracts and their active components, and some of their nano-encapsulated forms have been discussed.

Keywords: Chemotherapy; Complementary and alternative medicines; Cancer hepato and cyto-toxicities; Plant extracts; Plant products; Combined therapies


CAM: Complementary and Alternative Medicines; FDA: Food And Drug Administration; NCCAM: National Center for Complementary and Alternative Medicine; WHO: World health organization


Cancer has been earmarked as one of the major global public health concerns [1]. Its frequency of occurrence and the rate at which it causes fatality continue to be a serious health problem. A survey in 2008 by the World Health Organization (WHO) [2] estimated about 12.7 million people to be affected with cancer and among them, some 7.6 million people died from cancer worldwide. Further, if we go by the prediction of WHO, then the scenario would be really grave by 2030 when an estimated 21.4 million new cases of cancer will occur, resulting in death of some 13.2 million cancer patients annually around the world. Surgery, chemotherapy and radiotherapy, the present day weapons would hardly be sufficient to tackle a problem of such a magnitude, and newer avenues must be explored utilizing knowledge emerging in medical regimens such as complementary and alternative medicines (CAMs), at least for use as supportive medicines for alleviating toxicity produced by conventional therapy, apart from the more conventional orthodox medicines for providing a better way of life and longevity to the cancer patients.

Conventional chemotherapy means the treatment of disease specially cancer by the use of chemical substances and regimens that have been in use for the past fifty years or so. Conventional chemotherapy is given with one drug at a time or few drugs at one time or combined with other cancer treatments, like radiation therapy, surgery followed by several cycles of chemotherapy. In general, chemotherapeutic drugs effectively damage the fast proliferating cells and prevent mitosis by hampering DNA synthesis and inhibition of the cellular machinery involved in cell cycle process, which in turn induce apoptosis, a programmed cell death [3]. Alkalyting agents are the oldest chemotherapeutic agents that have been used since the late 1940s after it became known that the use of mustard gas in the World War I caused leucopenia [4,5]. It is proved that different drugs can destroy tumor cells by triggering common apoptotic pathways but mode of molecular events required for activation of apoptosis process is different [6].

Although chemotherapy is the key way to control cancer but due to a difficulty in dosage selection, lack of specificity which produces Cytotoxicity to normal cells as well, rapid drug metabolism, both intrinsic and acquired drug resistances varying in patient status and mainly harmful side effects, success of chemotherapy has been limited so far. On the other hand, certain complementary and alternative medicines (CAM) have occasionally been claimed [7-9] to have anticancer potentials and have no or negligible side-effects, which prompted us to examine if they could be used with potential benefits to the patients, at least by lessening/ameliorating their sufferings and pains that arise due to the disease as well as the side-effects of the chemotherapeutic drugs.

Data Source and Methods

A comprehensive search was made by utilizing data from the Pubmed, Cochrane Library, Embase and ISI Web of Knowledge, WHO and NCCAM reports and some related books to gain insight into the modern trend of research to combat the obstacles that come in the way of waging a successful war against cancer. Our focus was mainly on delineating the major problems encountered in chemotherapy and possible conjoint use of some herbal products and dietary supplements that could be beneficial to the abatement of sufferings and pains of the patients undergoing simultaneous orthodox treatment.

Problems of chemotherapy: Side-effects

Chemotherapeutic drugs are designed on the basis of their killing ability of cells that grow faster, the main characteristic feature of cancer cells. However, chemotherapeutic drugs also kill normal cells that divide; e.g. bone marrow cells, gut cells, etc. For this reason, the range and effectiveness of chemotherapy becomes restricted.

The growing capability of cancer cells to resist the chemotherapeutic drug is one of the main drawbacks of conventional chemotherapy. In drug-resistant cancer cells, expression of surface small pump like p- glycoprotein and intercellular antioxidant efflux prevent the chemotherapeutic agents from entering into the cells [10]. Many critical molecular types of machinery are involved in chemotherapeutic drugs and tumor cell interactions. Genotoxic drugs used in chemotherapy may induce alteration of gene expressions causing aggravation of DNA damage, resulting in cell death. But sometimes, structural changes in protein induced by genetic mutation prevent binding of drug with target protein, which in turn can resist the chemotherapeutic effect [11]. Acquired capabilities of cancer cells to produce gene amplification and alteration of gene expressions by mutation on coding genes for apoptosis-inducing proteins play an important role in generating resistance against chemotherapeutic drugs [4]. Defect in apoptotic pathway by genetic alteration of normal cells that involve in tumor genesis can also resist the chemotherapeutic drugs which kill the cancer cells by apoptosis. Thus, mutation in genes involving development of cancer cell can prevent apoptosis and also play important role in drug resistance.

Over-dosage in chemotherapy can produce much harmful effects in the patients. Therefore, much care has to be taken to determine the effective dosage. Several factors like body surface area (BSA) formula, mathematical calculation on the basis of the patients’ weight and height had been approved in early 1950s for calculating individual chemotherapeutic dosage. The effectiveness of chemotherapeutic drug varies with concentration of the drug in the patient’s bloodstream which is subjected by multiple factors, including metabolism, cancer state, drug- target interactions, and patients’ physiological and genetically state [12]. Now-a-days researchers are trying to establish a formula by which individual patient can achieve optimal systemic drug exposure which can maximize the drug efficacy and minimize cytotoxic effects.

Determination of cancer type and cancer stage is a very important phenomenon for success of chemotherapy. In certain cancer type where drug delivers through circulatory system, chemotherapy fails because of improper blood vessel in tumor cells [13]. Patients with late stage cancer may not fully cure and face greater risk of early death because they may not tolerate chemotherapeutic side-effects. Thus, side-effects are one of the major and leading problems of chemotherapy and often limit its use [14].

Side-effects occur mostly when the chemotherapy damages the healthy cells that maintain the body’s function and appearance. Different side-effects arise depending on the nature of the drug. As for example, the Alkalyting agents and anti metabolites directly damage DNA to prevent the cancer cells from reproducing; thus they can cause long-term damage to the bone marrow, which can eventually lead to acute leukemia. Similarly, Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in DNA replication. These drugs work in all phases of the cell cycle. A major consideration when giving these drugs is that they can permanently damage the heart if given in high doses for a long time. For this reason, lifetime dose limits are often put on place on these drugs. In the same way, some plant alkaloids and other compounds derived from natural products are often known to be mitotic inhibitors. They can stop mitosis or inhibit enzymes from making proteins needed for normal cell reproduction. These drugs are known for their potential to cause peripheral nerve damage, which can be a dose-limiting side effect. Likewise, topoisomerase inhibitors that cause DNA damage to cancer cells produce harmful side effects like symptoms of allergic reaction including fast heartbeat, itching or hives, swelling in the face or hands, swelling or tingling in the mouth or throat, chest tightness, and wheezing. Cytotoxic medicines are generally very powerful but often cause many unwanted side-effects. Since cytotoxic medicines mainly work by killing cells in their divisional stages, irrespective of whether they are normal or cancer cells, protection to normal cells is of prime importance while a patient is undergoing cancer therapy.

Immune-suppression during chemotherapy causes various sideeffects also. Bone marrow suppression decreases the production of blood cells leading to anemia and thrombocytopenia. Another serious problem of immune compromised patients, caecitisis-infection of the gut- includes diarrhea, nausea, vomiting, fever and distended abdomen etc [15]. Prolonged autoinfection manifests as systemic disease conditions like sepsis [16].

In early stage of chemotherapy mucositis, a painful inflammation and ulceration of mouth begins by damaging of normal cells lining the mouth [17]. Chemotherapeutic drugs target rapidly dividing cells like gastrointestinal cells resulting in nausea, vomiting, anorexia, diarrhea, abdominal cramps, and constipation etc. Gastrointestinal damage causes gastro paresis, decreased gut motility or delayed emptying of the stomach and small intestines leading to malnutrition and dehydration [18]. Fatigue, one of the most frequent and long lasting side-effects of chemotherapy, is a very problematic issue and it imposes limitations on normal daily activities of about 70% patients [19,20]. Every chemotherapeutic agent targets and damages fast dividing hair follicles resulting in vigorous hair loss leading to certain type of alopecia like alopecia totalis, telogen effluvium, or less often alopecia aerate [21]. Some Alkalyting chemotherapeutic agent constructs secondary neoplasia like acute myeloid leukemia which increases in frequency [22]. It has been observed that many chemotherapeutic patients lack their interest in sex [23]. Infertility arises in both female and male patients by some gonad toxic chemotherapeutic agents [24]. During pregnancy chemotherapy makes congenital abnormalities including growth retardation, delayed mental development or other congenital disorders [25]. Patients may suffer from peripheral neuropathy, a damage or disease affecting nerves which produces symptoms like numbness, abnormalities in brain and spinal cord, tremor, and gait abnormality [26]. Many chemotherapeutic agents cause non-specific neuro-cognitive problems in which patients suffer from inability to concentrate. Some chemotherapeutic drugs rapidly break down and cancer cells in turn release chemicals from inside the cells producing high levels of uric acid, potassium, phosphate and calcium in the blood. One of the decisive problems during chemotherapy is damages inflicted on normal organs. Organspecific toxicities arise by specific chemotherapeutic agents. Most chemotherapeutic drugs generate many free radicals producing Cytotoxicity, which in turn causes DNA damage in the cells leading finally to apoptosis. Cardio toxicity, hepatotoxicity, nephrotoxicity and ototoxicity, are some of the leading problems generating from the non- specific cytotoxic nature of these chemotherapeutic drugs [27-30]. Chemotherapeutic drugs may also produce many other sideeffects like dry skin and mouth, water retention, dental problem, digestive problem, emotional difficulties etc.

Supportive approaches with conventional chemotherapy

In recent years, in the Western countries where the occurrence of various types of cancer is very high (about 80%) in the US cancer population [9,31], use of complementary and alternative medicines (CAM) is gaining popularity among cancer patients, particularly for alleviating Cytotoxicity and side-effects of orthodox therapy. More and more patients now solicit CAM treatment combined with conventional Western medicine (chemotherapy and/or radiotherapy), as this approach has been found to yield a better effect in providing supportive care for cancer patients. Further, CAM has been found to render great advantages in terms of increasing the sensitivity of chemo- and radio-therapeutics, along with reduction of side-effects and complications associated with these otherwise effective therapies, and thereby improving quality of life and survival time [32] of the patients.

Complementary and Alternative Medicine treatments (CAM)

Complementary and alternative medicines, as defined by NCCAM are a group of various nonstandard, unproven, and irregular medicines and health care systems, practices, and products that generally fall outside of mainstream or conventional medicines. However, the application of these nonstandard approaches is now widespread in cancer therapy [33-36]. According to WHO, “complementary” means to use “a non-mainstream approach” together with conventional medicine and “alternative” means to use “a non-mainstream approach in place of conventional medicine”. Alternative medicine is any practice that is put forward as having the healing effects of medicine, but is not always based on evidence gathered using the scientific method. Examples include new and traditional medicine practices such as homeopathy, naturopathy, chiropractic, and energy medicine, various forms of acupuncture, Traditional Chinese medicine, Ayurvedic medicine, and Christian faith healing. The US National Center for Complementary and Alternative Medicine (NCCAM) put CAM into the following categories: (i) alternative medical systems defined by complete systems of theory and practice like homeopathy and naturopathy, (ii) mind–body medicine defined by variety of techniques designed to enhance the mind’s capacity to affect bodily function and symptoms like meditation and prayer, (iii) biologically based therapies defined by using substances found in nature like dietary supplements, herbal products, etc., (iv) manipulative and body-based methods defined by manipulation and/or movement of one or more parts of the body like chiropractic, massage and energy therapies, (v) bio electromagneticbased therapies defined by involvement of the unconventional use of electromagnetic fields like pulsed fields and magnetic fields (Figure 1) [37].

Citation: Mondal J, Panigrahi AK and Khuda-Bukhsh AR. Conventional Chemotherapy: Problems and Scope for Combined Therapies with Certain Herbal Products and Dietary Supplements. Austin J Mol & Cell Biol. 2014;1(1): 10.