According to the WHO (WORLD HEALTH ORGANIZATION) cancer is the second major leading cause of death in the world which has now become the global burden to health care system. As we all know that, cancer treatment is expensive one which has become difficult to afford in developing countries with low income. Now, it is high time to find out the economical anticancer treatment which can be used as a sole agent or as adjuvant therapy with cancer treatment with minimal sides effects. For this purpose, there are many plants have been explored to find out their anticarcinogenic potential. Among them, PSIDIUM GUAJAVA or simply known as GUAVA plant has shown promising anti carcinogenic potential. Different parts of plants such as fruits, leaves bark, roots and branches has been studying for anti- cancer treatment. There are at least less than 50 in vitro and some in vivo studies are indicating anti cancerous potential of plant against cancer. Let’s discuss first something about cancer,
WHAT IS CANCER?
Cancer is simply abnormal growth of cells which do not simply follow signaling or instruction as normal body cells do or in simple words, we can say that there is imbalance between cell proliferation (increased) and cell death (decreased). Due to the following reasons, Cancerous cells show abnormal pattern of growth.
REASONS FOR ABNORMAL GROWTH OF CANCER CELLS
1. Cancerous cells do not undergo apoptosis (a programmed death of cells) while normal cells undergo apoptosis.
2. Cancerous cells of body exhibit metastasis a process in which tumor or cancer cells migrate from its point of origin to others parts of body.
3. Cancerous cells exhibit angiogenesis a process in which new blood vessels are formed which supply nutrients and oxygen to tumor cells and responsible for its growth and spread.
4. Cancerous cells modulate immune system of body due to which body unable to recognize it and it spread easily within the host body.
BIO ACTIVE COMPONENTS OF GUAVA
Phytochemicals, polyphenols, essential oils, carotenoids, Vitamin C, quercetin, kaempferol, lycopene, flavonoids, saponins, tannins, calcium, phosphorous, iron, Vitamin A, Vitamin B, beta- sitosterol, alkaloids, triterpenoids, guajonoic acid, uvoal, oleanolic acid, ursolic acid, apigenin, resveratrol.
ABOUT ENZYMES, PROTEIN AND SIGNALING PATHWAY INVOLVED IN CARCINOGENESIS
Besides bioactive components of guava, Let’s discuss about some enzymes, proteins and signaling pathway which promote carcinogenesis to easily understand the link between guava and its anti-carcinogenic potential.
COX- 2
COX-2 is an enzyme which promote tumorigenesis by producing hormone like substance PGE-2(prostaglandin E-2) which induce inflammation, proliferation, angiogenesis, metastasis, chemotherapy resistance and assist cancerous cells in escaping from immune response.
CYCLIN-D
It regulate cell cycle and in tumor over expression of cyclin-D promote carcinogenesis.
VEGF (VASCULAR ENDOTHELIAL GROWTH FACTOR)
It is secreted by tumor cells and by binding with VEGF receptors located on tumor cells the process of angiogenesis begins.
MMP (MATRIX METALLOPROTIANSE)
It is an enzyme which promote carcinogenesis by promoting metastasis and angiogenesis. Here, we will discuss its 2 types,
MMP-2
By stimulating angiogenic factors required for angiogenesis.
MMP-9
By breaking down extracellular barriers (ECM) and promotes metastasis along with angiogenesis.
IL-6
Interleukin-6 (IL-6) is a cytokine which overexpression promote tumorigenesis by inducing proliferation, angiogenesis and metastasis with the prevention of cancer cells from apoptosis.
IL-8
Interleukin-8 (IL-8) promotes carcinogenesis by inducing proliferation, angiogenesis and metastasis. It also supports cancer cells from immune response by modulating immune cells (neutrophils and macrophages) action against them.
PGHS
Prostaglandin endoperoxide H synthase is also known as cyclooxygenase (COX-1 and COX-2) is a rate limiting enzyme for prostaglandin production. Over expression of PGHS promote all the factors responsible for carcinogenicity along with inflammation.
ANDROGEN RECEPTORS BINDING IN PROSTRATE
Androgen are steroid hormone which after binding with androgen receptors promote growth of normal cells in prostrate through stimulation of genes while mutated genes in prostrate results in abnormal growth of cells when androgen binds with androgen receptors.
MITOGEN ACTIVATED PROTEIN KINASE (MAPK)
It is signaling pathway which translate extracellular signals into intracellular response to regulate growth of cells. Over activity of this pathway promote carcinogenesis.
PROTEIN KINASE B (Akt)
It is protein for signaling pathway. Overexpression may promote tumorigenesis.
MAMALIAN TARGET OF RAPAMYCIN (mTOR)
Mutation of mTOR promote uncontrollable growth of cells which result in tumorigenesis.
RIBOSOMAL S6 KINASE (S6K1)
Due to mutation S6K1 induce proliferation and promote metastasis.
NUCLEAR FACTOR KAPPA B (NF-kB)
NF-kB promote inflammation and control many cellular functions.
WHAT IS THE MECHANISM OF ACTION OF GUAVA FOR ANTI CARCINOGENIC POTENTIAL?
The following factors are supposed to be possible mechanism for anti- carcinogenic effects of guava or Psidium guajava.
HIGH ANTI OXIDANT ACTIVITY OF GUAVA
Guava is easily available and frequently consuming antioxidants rich fruit. High antioxidants as quercetin, vitamin C and kaempferol are responsible for reduction of oxidative stress by scavenge ring free radicals and inflammation which subsequently reduces the risk of cancer. Now the question is that,
WHAT IS OXIDATIVE STRESS?
Oxidative stress is the condition in which free radicals are formed due to deficiency of anti-oxidants nutrients in the body. These free radicals damage body cells and tissues and may provoke many ailments as diabetes, Alzheimer, arthritis and cancer. Due to oxidative stressfree radicals may mutate body cell and become leading factor for different types of cancer.
ANTIPROLIFERATIVE ACTIVITY OF GUAVA
As we know that in cancerous cells, there is abnormal proliferation of cells which subsequently result in abnormal growth of cells. Presence of quercetin, resveratrol, guvjadial and guvainoside inhibit the abnormal proliferation of cells and act as anti-proliferative against cancer.
INDUCTION OF APOPTOSIS
By modulating immune system, cancerous cell does not undergo apoptosis while guava due to presence of powerful and potent antioxidant induce apoptosis by inhibiting signaling pathway as S6K1, mTOR, Akt and MAPK which results in suppression of tumor.
ANTI METASTASIS (INHIBITION OF METASTASIS)
As we already discussed, metastasis is migration of tumor cells from original or primary site to secondary site via blood or lymphatic system. Guava due to presence of APIGENIN, polyphenolic compound, flavonoids with the high antioxidants capacity mediated nutrients work synergistically against metastasis and could be a powerful anti-migration or anti-metastasis agent.
ANTI ANGIOGENESIS
Formation of new vessels for tumor cells survival is termed as angiogenesis. Guava by inhibiting pro-angiogenic factors stimulation as COX-2, VEGF, MMP-2, MMP-9, Cyclin-D, IL-6 and IL-8 suppress angiogenesis and ultimately tumor growth.
INHIBITION OF MUTATED GENE (ONCOGENE)
Oncogene can be defined as mutated gene responsible for abnormal growth of cancerous cells. Guava extract due to presence of lycopene and other antioxidants inhibit oncogenes which may promote carcinogenesis through PGHS and by binding of androgen with its receptors (ARs).
REDUCTION OF INFLAMMATION
Guava reduces prostaglandin secretion, blocks NF-kB and others inflammatory pathway whose overactivation responsible for carcinogenesis.
IMMUNE RESPONSE
Guava by boosting immune response through T helper cells, IL-2(interleukin)and INF(Interferon) gamma helps in suppression of tumor.
IS GUAVA EXTRACT DAMAGE NORMAL BODY CELLS?
No, guava is not cytotoxic to normal cells but effective against the cancerous cells which can prevent the patients from chemo-therapy hazards in future.
CONCLUSION
Future studies and research will definitely assist us in exploring guava anticarcinogenic potential. However, it is inexpensive and good fiber diet which should be used as adjuvant therapy along with chemotherapy.