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Chemopreventive Potential Of Curcumin In Prostate Cancer

Chemopreventive Potential Of Curcumin In Prostate Cancer

One of the most commonly diagnosed diseases in the world is prostate cancer. Because it is most commonly occurs in people in their sixties and seventies; even a small delay in disease progression could have a considerable influence on illness-related morbidity, mortality, and quality of life. Although the molecular processes behind the onset and progression of prostate cancer are unknown; age, race, diet, androgen production and metabolism, as well as activated oncogenes, have their implications in the disease’s pathogenesis. Surgery, radiation therapy, and hormonal therapy are all options for treating localised illness; but clinical care for advanced prostate cancer is difficult. Doctors most commonly recommend Androgen ablation therapeutic options for prostate cancer; but it is a palliative treatment with limited application in hormone-refractory tumours. Furthermore, chemotherapy and radiation therapy are inefficient in the treatment of advanced prostate cancer.

The development of innovative drugs to treat and prevent advanced prostate cancer is necessitated by the continued rise in incidence and failure of current therapy. Chemoprevention with naturally occurring chemicals has evolved in recent decades as a viable and cost-effective way of lowering the incidence and morbidity of prostate cancer by blocking precancerous processes even before the clinical illness. Because of its high incidence and long latency, prostate cancer offers a huge window of opportunity for intervention to prevent or halt its growth; and it remains a good target for chemoprevention in many aspects. As a result, developing medications that provide significant protection against the onset of this disease is extremely desirable.

For a broad segment of the population, such chemopreventive drugs could have a considerable impact on disease-related expenditures, morbidity, and mortality. Scientists use the data from a range of sources; including epidemiological, clinical, and pre-clinical investigations, to identify drugs and their molecular targets for prostate cancer chemoprevention. Prostate cancer, like other types of cancer, arises through changes in multiple molecular events; therefore blocking or inhibiting just one of them may not be enough to prevent or postpone the disease start.

As a result, continued research to better understand the condition and create novel prevention and treatment options is crucial. Epidemiological evidence suggests that people who eat more major phytochemical-rich foods have a lower incidence of prostate cancer. These findings have sparked enough interest in the scientific community; to investigate the use of natural substances in the prevention of prostate cancer. Scientists are now investigating the chemopreventive potential of several naturally occurring phytochemical substances like lycopene, capsaicin, curcumin and others.

Curcumin, a primary yellow pigment present in turmeric, is the most common spice in India; bringing flavour and colour to dishes. Turmeric has a long history of medical use in Asia; particularly in Ayurveda and Chinese cultures, where people use it to treat a number of inflammatory disorders and chronic diseases’1. Many of its traditional qualities, including anti-carcinogenic action, have do ensure cellular and animal disease models. Researchers have alos investigated curcumin and its active metabolites, like tetrahydrocurcumin, extensively for their anti-inflammatory and anti-carcinogenic properties. 

Uncontrol AR gene amplification, AR mutations, and an increase in AR expression accelerate the progression of prostate cancer to a hormone-refractory state. Curcumin inhibits AR expression and AR-binding activity to the PSA gene’s androgen response element. PSA expression is similarly decreases in LNCaP cells. The homeobox gene NKX3.1 is inhibited when AR expression is reduced and its DNA-binding activity is blocked by curcumin. This gene is important in both normal and cancerous prostate organogenesis.

According to studies, curcumin has been shown to decrease the growth of LNCaP and DU 145 cells in cell proliferation. In response to cellular cues such as stress or DNA damage, curcumin causes apoptosis in prostate cancer cells. Curcumin can activate caspases and down-regulate apoptosis suppressor proteins while up-regulating pro-apoptotic proteins from the Bcl-2 family. It also inhibits MDM2 protein and microRNA, a key negative regulator of the p53 tumour suppressor that allows prostate cancer cells to die.

Curcumin is rapidly metabolises, conjugating in the liver, and eliminates in the faeces, resulting in low systemic bioavailability, according to preclinical models. It appears to be quite safe and may have therapeutic value, according to several phase I and phase II clinical trials. Patients tolerate curcumin at dose levels of up to 3600 mg for up to four months in patients with advanced colorectal cancer and up to 8000 mg for up to three months in 25 patients with diverse precancerous lesions in phase I clinical trial to establish its toxicity.

These findings are encouraging, and interest in curcumin as a preventative and therapeutic agent is growing. A number of human trials studying curcumin’s chemopreventive or therapeutic potential in a variety of pre-malignant and cancer disorders have been completing or are now continuing, but none of them particularly target prostate cancer prevention or therapy. The results of all pre-clinical studies clearly support curcumin as a potential anticancer therapy. However, there is a need for more research to determine the mechanisms by which its bioavailability can increase and to investigate possible combination regimens for the prevention and treatment of prostate cancer.

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