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Cancer is the second leading cause of death worldwide next to cardiovascular disease. 40% of cancers can be prevented by reducing the exposure to risk factors. The incidence of cancer worldwide is 18 million, 9. 5 million in men and 8. 5 million in women in 2018. In men the common cancers are the lung, prostate, colorectal, stomach and liver cancers and in women breast, colorectal, lung, cervical and thyroid cancers.
Lung and breast cancers are the commonest in males and females respectively with the worldwide incidence of 2 million in the year 2018. According to the report of National Institute of Cancer Prevention and Research, in India the commonest cancers in men are oral, lung, stomach, colorectal and pharynx and in women, breast, cervix, ovary, oral and colorectal cancers. Colorectal cancer: Colorectal cancer (CRC) is the third common cancer in world in men and second most common cancer in women. It is common in developed nations and occurs mostly above the age of 50 years. CRC accounted for incidence of 12. 7 million and 7. 6 cancer deaths in 2008. In 2012 the incidence of CRC was 13, 60, 000 and the number of deaths was 6, 94, 000 worldwide. In 2018 the incidence of CRC was 18, 49, 518 and the number deaths was 38. 9/lakh (ASR- Age Standardized Rate). The 5 year prevalence of melanoma till September 2018 is 46, 62, 036. In India the calculated annual incidence was 1, 11, 427 in 2014. In India up to September 2018 the incidence of melanoma is 3048, mortality is 2053 and the prevalence is 7331. The global mortality due to CRC is 6, 08, 000 accounting for 8% of all cancer related deaths. Considering the increasing disease burden, mortality and its association with change in lifestyle CRC was taken for this study. Colorectal cancer is the cancer of the colon and the rectum. It is a slow growing tumor. Initially it starts from the mucosal layer of the colon or rectum. The lesion that arises initially is the polyp. Later it starts to invade the deeper layers of the colon wall. Then invading all the layers of the colon wall it spreads to the nearby tissues or distant organs like bone, lungs, liver, lymph nodes and others via blood or lymphatic. If detected early the disease is curable.
The risk factors for colorectal cancer are the old age, food habits, western life style, long term inflammatory diseases like Ulcerative colitis and Crohn’s disease and genetic factor. Regular physical exercise, fiber rich food intake and reducing junk food could significantly reduce the occurrence of colorectal cancer.
Initially there will not be any symptoms. Progression of the disease gives rise to symptoms like change in bowel habits (diarrhea/constipation), loss of appetite, loss of weight, passing blood/mucous in stool, abdominal distension and abdominal pain. Diagnosis: Colonoscopy is done to identify any mass present in the colon and if present biopsy is done to study the histopathology of the tissue to find whether it is cancer or not. Computed Tomography (CT) of abdomen helps to find the spread of the cancer to other tissues. MRI pelvis is done in case of rectal carcinoma.
If the cancer is confined to the colon or rectum simple excision of the tumor is done. If lymph node involvement is there chemotherapy with different pharmacological agents is given post-operatively. Radiotherapy is also given in case of metastasis.
These agents are given alone or in combination with other anti-cancer agents or immunosuppressants or as an adjuvant for radiotherapy or after surgery. The duration of therapy depends upon the progression of tumor. The success rate with the single agent therapy is low. In case of multiple agent therapy the success rate is high, but the adverse effects are also high. The side effects depend on the dose and type of drugs. The common side effects are myelosupression that leads to decreased blood cell count (anemia, leukemia and thrombocytopenia), bleeding due to thrompocytopenia; hepatotoxicity, neurotoxicity, nephrotoxicity, teratogenicity, cardiotoxicity and opportunistic infections. Chemotherapy affects the rapidly proliferating cells which include cancer cells and normal rapidly multiplying cells like mucosal cells of mouth and GIT, hair follicles which leads to gastrointestinal distress causing nausea and vomiting, mouth ulcers and alopecia. Some of these adverse effects are life threatening. Hence there is always a need for discovery and development of new drugs for CRC which will have equal efficacy but more safety and acceptability.
The second cancer taken for evaluation in this study was malignant melanoma. Melanoma: Melanoma accounts for 1-3 percentage of all cancers in the world. The global incidence and deaths of melanoma were 2, 32, 000 and 55, 000 in 2012.  In 2018 the incidence raised to 2, 87, 723 and the number of deaths was 60, 712. The 5 year prevalence for CRC is 9, 65, 623. In India the incidence of melanoma was 2103 in 2012. In 2018 the incidence and deaths were 3048 and 2053. The 5 year prevalence of melanoma in India is 7331. The incidence of melanoma is steadily on the increase. The five year survival rate for cutaneous melanoma is reported to be 25. 2% and 6. 6% for mucosal melanoma at 3 years. Though the incidence is low when compared to CRC, it was shown that the incidence is rising rapidly for past 50 years globally. Hence this cancer was also taken up for this study.
Melanoma is mainly a skin cancer but it can also affect other organs like eyes, inner ear and nervous system. It arises from the melanocytes of skin. Melanocytes are the pigment producing cells that are present in epidermis, hair follicles, mucosa, cochlea of ear, iris of eye and mesencephalon (brain). Melanocytes originate from neural crest and produce eu-/pheo melanin pigment in melanosome, a membrane bound organelle. Eumelanin gives dark brown and black colour whereas pheomelanin gives light brown, red and yellow color. It is noted that UV irradiation and polymorphism in genes MC1R (melanocortin 1 receptor) and CDKN2A (cyclin dependent kinase inhibitor 2A) causes melanoma. MC1R is the gene that encodes the receptor for melanocyte stimulating hormone. It controls melanogenesis and determines the normal pigment variation. Mutation of this gene causes loss of function which leads to increased pheomelanin production. Normally pheomelanin increases the sensitivity to UV radiation. Hence mutation of this gene can lead to melanoma. CDKN2A is cyclin dependent kinase inhibitor 2A, that encodes two proteins namely p16 and p14arf. These proteins are the tumor suppressors that regulate cell cycle. Mutation of this gene also can lead to melanoma.
The common cause for melanoma is reported to be excessive sun light exposure. Ozone layer covers and protects the earth from the UV rays that reaches from the sun. Because of global warming and pollution, the ozone layer has been thinned. This permits the easy entry of ultra violet rays, exposure of which causes not only melanoma but also other skin cancers.
Melanoma is treated depending upon the stage of the disease. Usually surgical removal of tumor is the primary mode of treatment. In case of advanced disease where the tumor cells spreads to the lymph nodes or the distant organs, adjuvant therapies are needed along with surgical removal. The adjuvant therapies are add-on therapies which include targeted therapy, immunotherapy, chemo therapy and radiation therapy. They are also used in case of un-resectable melanoma as a palliative therapy which shrinks the tumor and gives symptomatic relief. These agents are given alone or in combination with other anti-cancer agents or immunosuppressant or as an adjuvant for radiotherapy or after surgery. The duration of therapy depends upon the progression of tumor. Even though these agents are effective in melanoma, mostly the duration of therapy takes years and blood cell counting is mandatory before each cycle as these drugs suppresses bone marrow. These drugs have many adverse effects such as nausea, vomiting, alopecia and more importantly myelosupression; drug specific- nephrotoxicity, hepatotoxicity, pulmonary fibrosis, immune mediated enterocolitis and dermatitis. These side effects incapacitate the patients and compromise the compliance to treatment. The death rate due to melanoma among black men is reported to be 69% whereas 94% in white men. Anti-cancer treatment related deaths up to 11% within 30 days has been reported. Hence finding out equally effective drugs, but safer than the existing drugs is always a necessity.
Many medicinal plants are used in the traditional systems of medicine for treatment of cancer. Some of them include Colchicum Autumnale, Betula Alba, Camptotheca Acuminata, Taxus Baccata, Cannabis sativa and others. Among the medicinal plants Jackfruit (Artocarpus heterophyllus – AH) tree is unique that it bears the largest edible fruit. Jack fruit is consumed widely all over the globe. AH belongs to Moraceae family. It is cultivated widely in the tropical countries like India, Bangladesh and many Southeast Asia. It is the largest tree fruit in the world. Jack fruit cultivated in India as early as 3000 – 6000 years ago.  This is the national fruit of Bangladesh. The tree reaches 28 to 80 feet in height that is easily accessible for its fruit. The fruit is borne on side branches and main branches of the tree. Average weight of a fruit is 3. 5 – 10kg. It has many nutritional and medicinal values. Jackfruit pulp contains 74% of water, 23% of carbohydrates, 2% of protein and 1% of fat. 100 grams of fruit contains 94 kcal. AH contains many phyto compounds such as artocarpin, artocarpesin, nor-artocarpetin and oxyresveratrol which have been proved to have anti-inflammatory property. It is a rich source of potassium, which helps in reducing blood pressure as well as maintains muscle and nerve function. It contains thiamine, niacin and riboflavin called as B-vitamins helps in maintaining nerve function. It contains pyridoxine which reduces homocysteine level. Jack fruit is a good source of vitamin-C which improves the absorption of calcium which in turn maintains bone mineralization and prevents osteoporosis. Vitamin-C improves gum health and scavenges free radicals by acting as an anti-oxidant. Vitamin-C improves the synthesis of collagen which maintains the structure, firmness and strength of the skin to maintain good skin health. It contains copper which maintains thyroid hormone production.
AH also contains lectin which shows inhibitory activity against herpes simplex virus 2, varicella zoster virus and cytomegalovirus in in-vitro assay. The anti-oxidants vitamin-E, carotenoids, flavonoids and glutathione present in AH aid in the prevention of chronic degenerative disorders like cancer, inflammation, cardiovascular diseases, cataract and age related macular degeneration. Jack fruit contains phytonutrients like lignans, isoflavones and saponins that have anti-cancer, anti-hypertensive, anti-peptic ulcer and anti- aging properties. These phytochemicals slow down the degeneration of cells and the aging process. Because of many essential vitamins and nutrients, jack fruit is called functional food.
Anti-inflammatory Effect: The phytochemicals possessing anti-inflammatory property have been isolated from jack fruit extract. They have been shown to inhibit pro-inflammatory mediator production in LPS (lipopolysaccharide) activated RAW 264. 7 murine macrophage cells.
Antioxidant Effect : The two compounds namely cycloheterophyllin and artonins A and B present in Artocarpus heterophyllus were shown to possess significant anti-oxidant property. Antifungal Effect : Silver nanoparticles synthesized using leaf extract of Artocarpus heterophyllus (AH) have shown anti-fungal activity against Aspergillus nigar and Pichia pastoris.
Immunomodulatory effect: Jacalin is a lectin obtained from Artocarpus heterophyllus seed shown to possess immunomodulatory activity. It is used in the immune status evaluation of patient with HIV-1 infection and many other diagnostic purposes.
Antidiabetic effect: The aqueous leaf extract of AH improved glucose tolerance in normal and maturity onset diabetes patients.
Antibacterial Effect: Different extracts of AH leaves, fruit, seed, bark, stem and root have been shown to possess anti-bacterial activity against many bacteria like E. coli, S. aureus, B. subtilis and P. fluorescens.
Antiviral activity: Jackfruit leaf extract showed anti-viral activity against Hepatitis-C virus. Jack fruit lectin shown anti-HSV (Herpes simplex virus) and anti-CMV (Cytomegalovirus) activity.
Anthelmintic Effect The shoots showed nematocidal activity against some plant nematodes – Rotylenchulus reniformis, Tylenchorhynchus brassicae, Tylenchus filifofmis and Meloidogyne incognita.
Analgesic activity: Methanolic extract of Artocarpus heterophyllus leaves showed significant analgesic activity.
Inhibition of melanin biosynthesis: A series of prenylated, flavones based polyphenols isolated from the wood of Artocarpus heterophyllus showed inhibitory activity against in-vivo melanin biosynthesis in B16 melanoma cells.
Anti-cancer activity: AH seed, wood, bark and root were shown to possess anti-cancer activity against lung, breast, cervical, liver, melanoma, colorectal cancers. The AH skin was shown to possess anti-cancer activity against liver, breast, cervix and bone sarcoma. But the anti-cancer activity of AH skin was not evaluated against melanoma and colon cancer. Hence this study was planned to find out the anti-cancer activity of AH skin against human melanoma and colon cancer cells by two in-vitro methods, MTT and LDH assays.
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