ANTI - CANCER EFFECTS OF PLANT SECONDARY METABOLITES AGAINST VARIOUS CANCER

 

1. INTRODUCTION

     Secondary metabolites are not essential for the growth and development of plants, but they have important accessory activities such as help in defence against herbivory, growth inhibition of competing plants, bacterial and fungal pathogens and aiding in pollination. Notable anticancer alkaloids include vinblastine, vincristine and camptothecin; terpenoids include lycopene and gamma-tocopherol; polyphenols include etoposide, resveratrol, curcumin and epigallocatechin gallate (EGCG); and flavonoids include apigenin, genistein and kaempferol. These bioactive compounds exert anticancer effects either independently or synergistically with other compounds through regulation of metabolic and signalling pathways, inhibition of enzymes vital for cancer progression, angiogenesis, microtubule assembly and inducing apoptosis.  

2. ANTI - CANCER EFFECTS OF PLANT SECONDARY METABOLITES

     The hallmark of a cancer cell is its uncontrolled rate of proliferation. A cancer cell alters its physiology to meet the nutritional and energy requirements. In case of scarcity of nutrients and energy, cancer cells are able to modulate their pathways and continue proliferation. These alteration are in the form of modification in metabolic pathways, signalling pathways an enzymatic regulation.  These metabolic alteration mainly focus on rapid ATP production, synthesis of macromolecules needed for cell progression and regulation of appropriate redox state. 

     By understanding those pathways, researchers used different secondary metabolites from plants against Various Lung Cancer.

2.1. ANTICANCER EFFECT OF NARINGENIN AGAINST BREAST CANCER

In 2015, Using the concept of Warn burg Effect, throne and Campbell it has been reported that glucose transporters (GLUT) are up - regulated in cancer in a cell - specific manner. (The Warburg and colleagues made the observation that tumour cells produce energy predominantly not through the usual citric acid cycle and oxidation phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of high level of glucose uptake and glycolysis followed by lactic acid fermentation).  Target GLUT presents a viable strategy for cancer inhibition and treatment. Plant extract have been shown to target GLUT. For example, naringenin, a flavonoid presents in grapes inhibits glucose uptake in MCF- 7 Breast cancer cell by inhibiting the phosphoinositide 3 - kinase (PI3K) pathway that regulate glucose transporter, GLUT 4. 

2.2. ANTICANCER EFFECTS OF DELPHINDIN AGAINST NON SMALL CELL LUNG CANCER

In 2017, Kim Ed et al, reported the antiangiogenic activity of delphinidin. Delphinidin is a flavonoid which is abundantly found in fruits, flowers and leaves of plants.  They found that delphinidin decreases the expression level of HIF - 1, which is a VEGF transcription factor. (VEGF - Vascular Endothelial Growth Factor is a homodimer glycoprotein, it is main key factor in the process of making new blood Vessels. These Vascular endothelium, a monolayer of endothelial cells, Constitutes the inner cellular lining of arteries, Veins and Capillaries and therefore is in direct contact with the components and cells of blood).  

ADVANTAGES 

 The Production of secondary metabolites from plant cells via in vitro techniques under aseptic conditions as the potential of providing an unlimited supply of targeted compounds. The PTC is not used to synthesize the Anticancer compounds but also biopharmaceuticals including therapeutics antibodies for other diseases. The advantage of the callus culture, is we can maintain the cell at the stationary phase by providing the unlimited supply of the target secondary compounds. 

• Because of their targeted action, these drugs have an effect on the cancer cells and mostly leave normal, healthy cell alone. Traditional chemotherapy is cytotoxic to most cells, meaning it can damage normal, healthy cells in addition to damaging and killing cancer cells. 
• For the Cancer stages, I, IIA, IIB, IIIB, IIIC, the target therapy is not need, but the Stage IV treatment which includes Target therapy with Angiogenesis inhibitor, Target therapy with Apoptosis Initiator. 

DISADVANTAGES

                                                 RESEARCH CARRIED OUT BY IIT MADRAS

• They collect the plant which synthesize the cyclopeptides as a secondary metabolites, which is used as target molecule against the cancer cells. 
• They collect from the Himalayas and the ooty region, then they cultivated that in the horticulture in IIT madras. After 3 years they begin the study by characterizing the different types of cyclopeptides in the plants.
  
  
• RESULT:  What they found is the plant species from Himalaya and ooty, which was cultivated in the IIT Madras, they show Different array of Peptides, and its also synthesize the new proteins which are not in the plants in the Himalayas. This study which concludes, there is high impact of Climatic and Geographical Variabilities. 

OVERVIEW OF NON - SMALL CELL LUNG CANCER

 

INTRODUCTION

Lung Cancer is the leading cause of Cancer related death worldwide, and approximately 85% of cases are related to cigarette smoking. Metastasis, which is common in lung cancer is a multi stage process, involved invasion into blood or lymph, extravasation and growth at a new site. This Blog gives a way to understand what is Non Small Cell Lung Cancer, and its types and stages and How they are treated using the Secondary Metabolites from the living organisms (Particularly and Plants).

ABOUT NSCLC

• NSCLC is the most common type  of lung Cancer. It comprises 80 - 85% of lung Cancer. 
• This NSCLC is a malignant tumour with extremely high Mortality.
• NSCLC, it name implies that the size of the cancer cell is larger than the Small cell Lung cancer cell, by viewed under the microscope.
• NSCLC is the common type of Lung Cancer.
• It stages from 0 - IV. It mean, we can classify the stage of the NSCLC, based on the 
• Because of the larger  in size, it grow and spread slowly compared to the SCLC.
• The most common subtype of NSCLC are: 

a) Lung Adenocarcinoma: This is a slow growing subtype. It often develops in the bronchi or airways of the lungs. 

b) Lung Squamous cell Carcinoma: This is the least common type of NSCLC. It can form in any part of the lung and tends to grow and spread rapidly.  

c) Large cell carcinoma: This  is the most common type of NSCLC. It typically begins in the outer tissues of the lung that secrete substances such as mucus. This type  is more likely to be diagnosed before it spreads. 

HOW THE NSCLC IS CAUSED

Tobacco smoking is the leading cause of cancer - related death in the world, having been associated to approximately 1.2 million death annually, and it is linked 90% of lung cancer cases. We can classify the Causes into 3 forms, Based on How we exposed to them: 

A) USING TOBACCO:

There are approximately more than 500 to 600 substances used in cigarette. When we burned cigarettes, it create more than 6000 chemicals. From those chemicals, 60 to 70 chemicals are known to cause cancer. Those chemical cancer causing substances are derived from various chemical classes such as Polycyclic aromatic hydrocarbons (PAHs), Nitrosamines, Aromatic Amines, phenols, volatile hydrocarbons, etc., Example: Acetone, Nicotine, Tar, Toluene are the example of the chemicals in tobacco smoke. 

B) SECONHAND TOBACCO SMOKE

Non - Smokers can be exposed to second-hand smoke from different sources, such as in the home, the workplace, and outside public building. Side stream smoke and mainstream second - hand smoke are different in their physiochemical Properties. The ration of side stream to mainstream smoke vary largely depending on the constituents of tobacco products from different manufactures. For example, nicotine, NNK, and NNN ratio can be 7.1, 0.40, and 0.43 respectively.    

C) SMOKE LESS TOBACCO

Smokeless tobacco is unburned tobacco, and is also known as chewing tobacco, oral tobacco, split or splitting tobacco, dip and snuff. Users chew or suck the tobacco in their mouth and split out the juice of the tobacco. However, a study by Hecht et.al., (2017) demonstrates that there is similar exposure to the tobacco - specific carcinogen NNK in smokers and smokeless tobacco users. 

MECHANISM OF NSCLC DEVELOPMENT:

EXAMPLE:  HOW NITROSAMINE COMPOUND INDUCING CANCER

Naturally occurring in tobacco smoke is a procarcinogen, an inert form that require metabolic activation to exert its carcinogenic functions. The Cytochrome P450 usually metabolizes carcinogens by converting the chemicals to more potent carcinogens, by activating the NNK (Nitrosamine compounds) into DNA reactive metabolites that can induce the methylation, pyridyloxobutylation and pyridylhdroxybutylation of nucleobases in DNA and form DNA adducts. The Repair mechanism either should repair the DNA adducts or apoptosis, if its fails it leads to Mutation in multiple genes and finally cancer. 

STAGES OF NON SMALL CELL LUNG CANCER

STAGE 0 - Non Invasive pre - cancer found in lining of airways.

 

STAGE 1 -  Invasive tumour hasn't spread to lymph nodes. 

STAGE 2 - Tumour is 3 to 7 cm and has spread to nearby tissues or lymph nodes, but not to distant body parts. 

STAGE 3 - Tumour is 3 to 7 cm and has spread to nearby tissues or lymph nodes, but not to distant body parts. 

STAGE 4 - Cancer has potentially spread outside the lung. 

TREATMENT FOR NON SMALL CELL LUNG CANCER: 

There are two method of Treatments are available for NSCLC. 

LOCAL TREATMENT:

Local treatment which are used to treat a specific tumour or area of the body. Example of the local treatment, like surgery and radiation therapy. 

TARGET THERAPY: 

Target therapy is a type of cancer treatment that uses drug designed to "target" cancer cells without affecting normal cells. Cancer cells typically have changes in their genes that make them different from normal cells. Genes are part of a cell's DNA that tell the cell to do certain things. When a cell has certain gene changes it doesn't behave like a normal cell.  

CONCLUSION: 

This is all about the Non small cell lung Cancer, I hope this will helps you to understand the basic concept of NSCLC, classification, Causes (especially tobacco), Stages and its therapies.